Immunogenic Composition for Use in Vaccination Against Staphylococcei

Abstract

The present application relates to immunogenic compositions comprising a mixture of staphylococcal antigens which combines antigen having different functions, for instance, combinations including a staphylococcal extracellular component binding protein and a staphylococcal transporter protein or a staphylococcal extracellular component binding protein and a staphylococcal regulator of virulence or toxin or a staphylococcal transporter protein and a staphylococcal regulator of virulence or toxin. Vaccines, methods of treatment, uses of and processes to make a staphylococcal vaccine are also described.

Description

TECHNICAL FIELD

[0001] The present invention relates to the field of Staphylococcal immunogenic compositions and vaccines, their manufacture and the use of such compositions in medicine. More particularly, it relates to vaccine compositions comprising a combination of antigens for the treatment or prevention of staphylococcal infection. Methods of using such vaccines in medicine and methods for their preparation are also provided.

BACKGROUND

[0002] The number of both community acquired and hospital acquired infections have increased over recent years with the increased use of intravascular devices. Hospital acquired (nosocomial) infections are a major cause of morbidity and mortality, more particularly in the US, where if affects more than 2 million patients annually. Following various studies, about 6 percent of the US patients will acquire an infection during their stay in hospital. The economic burden in the USA was estimated to be more than $4.5 billion in 1992 (Emori and Gaynes, 1993, Clin. Microbiol. Rev. 6; 428). The most frequent infections are urinary tract infections (UTI-33% of the infections), followed by pneumonia (15.5%), surgical site infections (14.8%) and primary bloodstream infections (13%) Emori and Gaynes, 1993, Clin. Microbiol. Rev. 6; 428).

[0003] Staphylococcus aureus, Coagulase-negative Staphylococci (mostly Staphylococcus epidermidis), enterococcus spp, Esherichia coli and Pseudomonas aeruginosa are the major nosocomial pathogens. Although those pathogens almost cause the same number of infections, the severity of the disorders they can produce combined with the frequency of antibiotic resistant isolates balance this ranking towards S. aureus and S. epidermidis as being the most significant nosocomial pathogens.

[0004] Staphylococcus aureus is the most common cause of nosocomial infections with a significant morbidity and mortality (Romero-Vivas et al 1995, Infect. Dis. 21; 1417). It is the cause of some cases of osteomyelitis, endocarditis, septic arthritis, pneumonia, abscesses and toxic shock syndrome.

[0005] S. epidermidis is a normal skin commensal which is also an important opportunistic pathogen responsible for infections of implanted medical devices and infections at sites of surgery. Medical devices infected by S. epidermidis include cardiac pacemakers, cerebrospinal fluid shunts, continuous ambulatory peritoneal dialysis catheters, orthopaedic devices and prosthetic heart valves.

[0006] S. aureus and S. epidermidis infections are treated with antibiotics with penicillin being the drug of choice whereas vancomycin is used for methicillin resistant isolates. The percentage of staphylococcal strains exhibiting wide-spectrum resistance to antibiotics has become increasingly prevalent since the 1980's (Panlilo et al 1992, Infect. Control. Hosp. Epidemiol. 13; 582), posing a threat for effective antimicrobial therapy. In addition, the recent emergence of vancomycin resistant S. aureus strain has aroused fear that methicillin resistant S. aureus strains will emerge and spread for which no effective therapy is available.

[0007] An alternative approach of using antibodies against staphylococcal antigens in passive immunotherapy has been investigated. Therapy involving administration of polyclonal antisera are under development (WO 00/15238, WO 00/12132) as well as treatment with a monoclonal antibody against lipoteichoic acid (WO 98/57994).

[0008] An alternative approach would be use of active vaccination to generate an immune response against staphylococci. Several candidates for inclusion as vaccine components have been identified. These include Fibronectin binding protein (U.S. Pat. No. 5,840,846), MHC II analogue (U.S. Pat. No. 5,648,240), fibrinogen binding protein (U.S. Pat. No. 6,008,341), GehD (US 2002/0169288), collagen binding protein (U.S. Pat. No. 6,288,214), SdrF, SdrG and SdrH (WO 00/12689), mutant SEA and SEB exotoxins (WO 00/02523) and 52 kDa vitronectin binding protein (WO 01/60852).

[0009] The S. aureus genome has been sequenced and many of the coding sequences have been identified (EP786519, WO02/094868). The same is true for S. epidermidis (WO 01/34809). As a refinement of this approach, others have identified proteins that are recognised by hyperimmune sera from patients who have suffered staphylococcal infection (WO01/98499, WO 02/059148).

[0010] The first generation of vaccines targeted against S. aureus or against the exoproteins it produces have met with limited success (Lee 1996 Trends Microbiol. 4; 162). There remains a need to develop effective vaccines against staphylococcal infections.

[0011] Accordingly the present invention provides an immunogenic composition comprising at least two different proteins or immunogenic fragments thereof, selected from at least two groups of proteins or immunogenic fragments selected from the following groups: [0012] Group a) at least one staphylococcal extracellular component binding protein or immunogenic fragment thereof selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig and MAP; [0013] Group b) at least one staphylococcal transporter protein or immunogenic fragment thereof selected from the group consisting of Immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC and Ni ABC transporter; [0014] Group c) at least one staphylococcal regulator of virulence, toxin or immunogenic fragment thereof selected from the group consisting of alpha toxin (Hla), alpha toxin H35R mutant, RNA III activating protein (RAP).

DESCRIPTION OF FIGURES

[0015] FIG. 1--Polypeptide sequences of preferred proteins. Table 1 provides information on which protein is represented by each SEQ ID.

[0016] FIG. 2--Nucleotide sequences encoding preferred proteins. Table 1 provides information on which protein is encoded by each SEQ ID.

[0017] FIG. 3--Purification of alpha toxin under native conditions. Panel A shows a coommassie stained SDS-PAGE of samples prepared during the purification of alpha toxin. Lane 1--molecular weight markers, lane 2--soluble fraction containing over-expressed alpha toxin, lane 3--flow through from the Ni-NTA column, lane 4--fractions eluted with 10% buffer B, lane 5--fractions eluted with 20% buffer B, lane 6--fractions eluted with 30% buffer B, lane 7--fractions eluted with 50% buffer B, lane 8--fractions eluted with 75% buffer B, lane 9 and 10 fractions eluted with 100% buffer B, lane 11 bacteria at T=0 before induction, lane 12--bacteria at T=4 hours after induction, lane 13--cell lysate, lane 14--soluble fraction, lane 15--insoluble fraction.

[0018] Panel B shows a coommassie stained SDS-PAGE of 10, 5, 2 and 1 .mu.l of the purified alpha toxin.

[0019] FIG. 4--Purification of SdrC underdenaturing conditions. Panel A shows a coommassie stained SDS-PAGE of samples prepared during the purification of alpha toxin. Lane M--molecular weight markers, lane Start--supernatant formed from the insoluble fraction containing over-expressed SdrC, lane FT1--flow through from the Ni-NTA column, lane C--fractions eluted with wash buffer C, lane D--fractions eluted with buffer D, lane E--fractions eluted with buffer E.

[0020] Panel B shows a coommassie stained SDS-PAGE of 1, 2, 5 and 10 .mu.l of the purified SdrC.

[0021] FIG. 5--ELISA results for antisera against staphylococcal proteins in plates coated with purified proteins.

[0022] Pool mice pre--result using pooled sera extracted from mice pre-innoculation. Pool mice Post III--result using pooled mouse sera extracted post-immunisation. Pool rabbit pre--result using pooled sera extracted from rabbits pre-innoculation. Pool rabbit Post III--result using pooled rabbit sera extracted post-immunisation. Blc--negative control.

[0023] FIG. 6--ELISA results for mouse antisera raised against staphylococcal proteins in plates coated with killed staphylococci.

[0024] Panel A uses plates coated with S. aureus serotype 5 killed whole cells. Panel B uses plates coated with S. aureus serotype 8 killed whole cells. Panel C uses plates coated with S. epidermidis killed whole cells.

[0025] The line marked with square signs shows the ELISA result using antisera from mice immunised three times with the indicated staphylococcal protein. The line marked with diamond signs shows the ELISA result for pre-immune mouse sera.

[0026] FIG. 7--ELISA results for rabbit antisera raised against staphylococcal proteins in plates coated with killed staphylococci.

[0027] Panel A uses plates coated with S. aureus serotype 5 killed whole cells. Panel B uses plates coated with S. aureus serotype 8 killed whole cells. Panel C uses plates coated with S. epidermidis killed whole cells.

[0028] The line marked with square signs shows the ELISA result using antisera from rabbits immunised three times with the indicated staphylococcal protein (except for HarA where only one immunisation was given). The line marked with diamond signs shows the ELISA result for pre-immune rabbit sera.

DETAILED DESCRIPTION

[0029] The present invention discloses particular combinations of Staphylococcal antigens which when combined, lead to the production of an immunogenic composition that is effective at treating or preventing staphylococcal infection. Immunogenic compositions of the invention suitably incorporate antigens which are involved in different staphylococcal functions. Such immunogenic compositions target the immune response towards different aspects of the staphylococcal function and are therefore able to induce a particularly effective immune response.

[0030] Staphylococcal infections progress through several different stages. For example, the staphylococcal life cycle involves commensal colonisation, initiation of infection by accessing adjoining tissues or the bloodstream, anaerobic multiplication in the blood, interplay between S. aureus virulence determinants and the host defence mechanisms and induction of complications including endocarditis, metastatic abscess formation and sepsis syndrome. Different molecules on the surface of the bacterium will be involved in different steps of the infection cycle. By targeting the immune response against an effective amount of a combination of particular antigens involved in different processes of Staphylococcal infection, a Staphylococcal immunogenic composition or vaccine with increased efficacy can be achieved.

[0031] In particular, combinations of certain antigens from different classes, some of which are involved in adhesion to host cells, some of which are involved in iron acquisition or other transporter functions, some of which are toxins or regulators of virulence and immunodominant antigens can elicit an immune response which protects against multiple stages of infection.

[0032] The effectiveness of the immune response can be measured either in animal model assays as described in the examples and/or using an opsonophagocytic assay as described in the examples.

[0033] An additional advantage of the invention is that the combination of antigens of the invention from different families of proteins in an immunogenic composition will enable protection against a wider range of strains.

[0034] The invention relates to immunogenic compositions comprising a plurality of proteins selected from at least two different categories of protein, having different functions within Staphylococci. Examples of such categories of proteins are extracellular binding proteins, transporter proteins such as Fe acquisition proteins, toxins or regulators of virulence and other immunodominant proteins. The vaccine combinations of the invention are effective against homologous Staphylococcal strains (strains from which the antigens are derived) and preferably also against heterologous Staphylococcal strains.

[0035] An immunogenic composition of the invention comprises a number of proteins equal to or greater than 2, 3, 4, 5 or 6 selected from 2 or 3 of the following groups: [0036] group a)--at least one staphylococcal extracellular component binding protein or immunogenic fragment thereof selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig and MAP; [0037] group b)--at least one staphylococcal transporter protein or immunogenic fragment thereof selected from the group consisting of Immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC and Ni ABC transporter; [0038] group c)--at least one staphylococcal regulator of virulence, toxin or immunogenic fragment thereof selected from the group consisting of alpha toxin (Hla), alpha toxin H35R mutant, RNA III activating protein (RAP).

[0039] For example a first protein is selected from group a), b) or c) and a second protein is selected from a group selected from groups a), b) and c) which does not include the second protein.

[0040] In a preferred embodiment, the immunogenic composition of the invention contains at least one protein selected from group a) and an additional protein selected from group b) and/or group c).

[0041] In a further embodiment, the immunogenic composition of the invention contains at least one antigen selected from group b) and an additional protein selected from group c) and/or group a).

[0042] In a further embodiment, the immunogenic composition of the invention contains at least one antigen selected from group c) and an additional protein selected from group a) and/or group b).

[0043] The immunogenic composition of the invention suitably contains proteins from S. aureus, and/or S. epidermidis.

Proteins

[0044] Immunogenic compositions of the invention comprise an isolated protein which comprises an amino acid sequence which has at least 85% identity, preferably at least 90% identity, more preferably at least 95% identity, most preferably at least 97-99% or exact identity, to that of any sequence of FIG. 1.

[0045] Where a protein is specifically mentioned herein, it is preferably a reference to a native or recombinant, full-length protein or optionally a mature protein in which any signal sequence has been removed. The protein may be isolated directly from the staphylococcal strain or produced by recombinant DNA techniques. Immunogenic fragments of the protein may be incorporated into the immunogenic composition of the invention. These are fragments comprising at least 10 amino acids, preferably 20 amino acids, more preferably 30 amino acids, more preferably 40 amino acids or 50 amino acids, most preferably 100 amino acids, taken contiguously from the amino acid sequence of the protein. In addition, such immunogenic fragments are immunologically reactive with antibodies generated against the Staphylococcal proteins or with antibodies generated by infection of a mammalian host with Staphylococci. Immunogenic fragments also includes fragments that when administered at an effective dose, (either alone or as a hapten bound to a carrier), elicit a protective immune response against Staphylococcal infection, more preferably it is protective against S. aureus and/or S. epidermidis infection. Such an immunogenic fragment may include, for example, the protein lacking an N-terminal leader sequence, and/or a transmembrane domain and/or a C-terminal anchor domain. In a preferred aspect the immunogenic fragment according to the invention comprises substantially all of the extracellular domain of a protein which has at least 85% identity, preferably at least 90% identity, more preferably at least 95% identity, most preferably at least 97-99% identity, to that a sequence selected from FIG. 1 over the entire length of the fragment sequence.

[0046] Also included in immunogenic compositions of the invention are fusion proteins composed of Staphylococcal proteins, or immunogenic fragments of staphylococcal proteins. Such fusion proteins may be made recombinantly and may comprise one portion of at least 2, 3, 4, 5 or 6 staphylococcal proteins. Alternatively, a fusion protein may comprise multiple portions of at least 2, 3, 4 or 5 staphylococcal proteins. These may combine different Staphylococcal proteins or immunogenic fragments thereof in the same protein. Alternatively, the invention also includes individual fusion proteins of Staphylococcal proteins or immunogenic fragments thereof, as a fusion protein with heterologous sequences such as a provider of T-cell epitopes or purification tags, for example: .beta.-galactosidase, glutathione-S-transferase, green fluorescent proteins (GFP), epitope tags such as FLAG, myc tag, poly histidine, or viral surface proteins such as influenza virus haemagglutinin, or bacterial proteins such as tetanus toxoid, diphtheria toxoid, CRM197. TABLE-US-00001 TABLE 1 The following table sets out the SEQ ID numbers of preferred protein sequences and DNA sequences that are found in FIG. 1 and FIG. 2 respectively. SA indicates a sequence from S. aureus and SE indicates a sequence from S. epidermidis. Name Protein sequence DNA sequence Immunodominant ABC transporter SA SEQ ID 1 SEQ ID 34 SE SEQ ID 2 SEQ ID 35 Laminin receptor SA SEQ ID 3 SEQ ID 36 SE SEQ ID 4 SEQ ID 37 Secretory Antigen A SsaA SA 1 SEQ ID 5 SEQ ID 38 SA 2 SEQ ID 6 SEQ ID 39 SE SEQ ID 7 SEQ ID 40 SitC SA SEQ ID 8 SEQ ID 41 SE SEQ ID 9 SEQ ID 42 IsaA/PisA (IssA) SA SEQ ID 10 SEQ ID 43 SE SEQ ID 11 SEQ ID 44 EbhA/B SA EbhA SEQ ID 12 SEQ ID 45 SA EbhB SEQ ID 13 SEQ ID 46 SE EbhA SEQ ID 14 SEQ ID 47 SE EbhB SEQ ID 15 SEQ ID 48 Accumulation-assoc pro Aap SA SEQ ID 16 SEQ ID 49 SE SEQ ID 17 SEQ ID 50 RNA III activating protein RAP SA SEQ ID 18 SEQ ID 51 SE SEQ ID 19 SEQ ID 52 FIG/SdrG SA SEQ ID 20 SEQ ID 53 SE SEQ ID 21 SEQ ID 54 Elastin binding protein EbpS SA SEQ ID 22 SEQ ID 55 SE SEQ ID 23 SEQ ID 56 Extracellular protein EFB SA SEQ ID 24 SEQ ID 57 alpha toxin SA SEQ ID 25 SEQ ID 58 SBI SA SEQ ID 26 SEQ ID 59 IsdA SA SEQ ID 27 SEQ ID 60 IsdB SA SEQ ID 28 SEQ ID 61 SdrC SA SEQ ID 29 SEQ ID 62 ClfA SA SEQ ID 30 SEQ ID 63 FnbA SA SEQ ID 31 SEQ ID 64 ClfB SA SEQ ID 32 SEQ ID 65 Coagulase SA SEQ ID 33 SEQ ID 66 FnbB SA SEQ ID 67 SEQ ID 71 MAP SA SEQ ID 68 SEQ ID 72 SdrC SA SEQ ID 69 SEQ ID 73 SdrG SA SEQ ID 70 SEQ ID 74

Extracellular Component Binding Proteins

[0047] Extracellular component binding proteins are proteins that bind to host extracellular components. The term includes, but is not limited to adhesins.

[0048] Examples of extracellular component binding proteins include laminin receptor (Naidu et al J. Med. Microbiol. 1992, 36; 177), SitC/MntC/saliva binding protein (U.S. Pat. No. 5,801,234, Wiltshire and Foster Infec. Immun. 2001, 69; 5198), EbhA (Williams et al Infect. Immun. 2002, 70; 6805), EbhB, Elastin binding protein (EbpS) (Park et al 1999, J. Biol. Chem. 274; 2845), EFB (FIB) (Wastfelt and Flock 1995, J. Clin. Microbiol. 33; 2347), SBI (Zhang et al FEMS Immun. Med. Microbiol. 2000, 28; 211), autolysin (Rupp et al 2001, J. Infect. Dis. 183; 1038), ClfA (U.S. Pat. No. 6,008,341, McDevitt et al Mol. Microbiol. 1994, 11; 237), SdrC, SdrG (McCrea et al Microbiology 2000, 146; 1535), SdrH (McCrea et al Microbiology 2000, 146; 1535), Lipase GehD (US2002/0169288), SasA, FnbA (Flock et al Mol. Microbiol. 1994, 12; 599, U.S. Pat. No. 6,054,572), FnbB (WO 97/14799, Booth et al 2001 Infec. Immun. 69; 345), collagen binding protein Cna (Visai et al 2000, J. Biol. Chem. 275; 39837), ClfB (WO 99/27109), FbpA (Phonimdaeng et al 1988 J. Gen Microbiol. 134; 75), Npase (Flock 2001 J. Bacteriol. 183; 3999), IsaA/PisA (Lonenz et al FEMS Immuno. Med. Microbiol. 2000, 29; 145), SsaA (Lang et al FEMS Immunol. Med. Microbiol. 2000, 29; 213), EPB (Hussain and Hermann symposium on Staph Denmark 14-17.sup.th 2000), SSP-1 (Veenstra et al 1996, J. Bacteriol. 178; 537), SSP-2 (Veenstra et al 1996, J. Bacteriol. 178; 537), 17 kDa heparin binding protein HBP (Fallgren et al 2001, J. Med. Microbiol. 50; 547), Vitronectin binding protein (Li et al 2001, Curr. Microbiol. 42; 361), fibrinogen binding protein, coagulase, Fig (WO 97/48727) and MAP (U.S. Pat. No. 5,648,240)

SitC/MntC/Saliva Binding Protein

[0049] This is an ABC transporter protein which is a homologue of adhesin PsaA in S. pneumoniae. It is a highly immunogenic 32 kDa lipoprotein which is distributed through the bacterial cell wall (Cockayne et al Infect. Immun. 1998 66; 3767). It is expressed in S. aureus and S. epidermidis as a 32 kDa lipoprotein and a 40 kDa homologue is present in S. hominis. In S. epidermidis, it is a component of an iron-regulated operon. It shows considerable homology to both adhesins including FimA of Streptococcus parasanguis, and with lipoproteins of a family of ABC transporters with proven or putative metal iron transport functions. Therefore SitC is included as an extracellular biding protein and as a metal ion transporter.

[0050] The saliva binding protein disclosed in U.S. Pat. No. 5,801,234 is also a form of SitC and can be included in an immunogenic composition of the invention.

ClfA and ClfB

[0051] Both these proteins have fibrinogen binding activity and trigger S. aureus to form clumps in the presence of plasma. They contain a LPXTG motif common to wall associated proteins.

[0052] ClfA is described in U.S. Pat. No. 6,008,341 and ClfB is described in WO 99/27109.

Coagulase (FbpA)

[0053] This is a fibrinogen binding protein which triggers S. aureus to form clumps in the presence of plasma. It is described in references related to Coagulase: Phonimdaeng et al (J. Gen. Microbio. 1988, 134:75-83), Phonimdaeng et al. (Mol Microbiol 1990; 4:393-404), Cheung et al. (Infect Immun 1995; 63:1914-1920) and Shopsin et al. (J. Clin. Microbiol. 2000; 38:3453-3456).

[0054] Preferred fragments for inclusion in the immunogenic composition of the invention include the mature protein in which the signal peptide has been removed (amino acids 27 to the C-terminus).

[0055] Coagulase has three distinct domains. Amino acids 59-297 which is a coiled coil region, amino acids 326-505 which is a proline and glycine rich region and the C-terminal domain from amino acid 506 to 645 which has a beta sheet conformation. Each of these domains is a preferred fragment of the invention.

SdrG-Fbe-EfB/FIG

[0056] Fbe is a fibrinogen binding protein that is found in many isolates of S. epidermidis and has a deduced molecular weight of 119 kDa (Nilsson et al 1998. Infect. Immun. 66; 2666). Its sequence is related to that of clumping factor from S. aureus (ClfA). Antibodies against Fbe can block the binding of S. epidermidis to fibrinogen coated plates and to catheters (Pei and Flock 2001, J. Infect. Dis. 184; 52). This protein is also described as SdrG in WO 00/12689. SdrG is found in coagulase negative staphylococci and is a cell wall associated protein containing a LPXTG sequence.

[0057] SdrG contains a signal peptide (amino acids 1-51), a region containing fibrinogen binding sites and collagen binding sites (amino acids 51-825), two CnaB domains (amino acids 627-698 and 738-809), a SD repeat region (amino acids 825-1000) and an anchor domain (amino acids 1009-1056).

[0058] Fbe has a putative signal sequence with a cleavage site between amino acids 51 and 52. Therefore a preferred fragment of Fbe contains the mature form of Fbe extending from amino acid 52 to the C-terminus (amino acid 1,092).

[0059] The domain of Fbe from amino acid 52 to amino acid 825 is responsible for fibrinogen binding. Therefore a preferred fragment of Fbe consists of or contains amino acids 52-825.

[0060] The region between amino acid 373 and 516 of Fbe shows the most conservation between Fbe and ClfA. Preferred fragment will therefore contain amino acids 373-516 of Fbe.

[0061] Amino acids 825-1041 of Fbe contains a highly repetitive region composed of tandemly repeated aspartic acid and serine residues.

[0062] Preferred fragments of SdrG include polypeptides in which the signal peptide and/or the SD repeats and the anchor domain have been removed. These include polypeptides comprising or consisting of amino acids 50-825, amino acids 50-633, amino acids 50-597 (SEQ ID NO 2 of WO 03/76470), amino acids 273-597 (SEQ ID NO 4 of WO 03/76470), amino acids 273-577 (SEQ ID NO 6 of WO 03/76470) amino acids 1-549, amino acids 219-549, amino acids 225-549, amino acids 219-528, amino acids 225-528 of SEQ ID NO:70.

[0063] Preferably, an SdrG polypeptide having a sequence at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or 100% homologous to the sequence of SEQ ID 70, 20 or 21 is incorporated into the immunogenic composition of the invention.

[0064] The compositions of the invention optionally comprise a fragment of the SdrG polypeptides described above.

[0065] Preferred fragments have the signal peptide and/or the SD repeat domain and/or the anchoring domain deleted. For example sequences corresponding to amino acids 1-713, 1-549, 225-549, 225-529, 24-717, 1-707, 1-690, 1-680, 1-670, 1-660, 1-650, 1-640, 1-630, 1-620, 1-610, 1-600, 34-707, 44-697, 36-689 of SEQ ID 76 or sequences having 85%, 90%, 92%, 95%, 97%, 98%, 99% or 100% identity to SEQ ID 70 or 20 or 21.

[0066] Preferred fragment with the signal peptide deleted have a methionine residue at the N-terminus of the fragment to ensure correct translation.

[0067] A more preferred fragment has the following sequence:-- TABLE-US-00002 MEENSVQDVKDSNTDDELSDSNDQSSDEEKNDVINNNQSINTDDNNQIIK KEETNNYDGIEKRSEDRTESTTNVDENEATFLQKTPQDNTHLTEEEVKES SSVESSNSSIDTAQQPSHTTINREESVQTSDNVEDSHVSDFANSKIKESN TESGKEENTIEQPNKVKEDSTTSQPSGYTNIDEKISNQDELLNLPINEYE NKARPLSTTSAQPSIKRVTVNQLAAEQGSNVNHLIKVTDQSITEGYDDSE GVIKAHDAENLIYDVTFEVDDKVKSGDTMTVDIDKNTVPSDLTDSFTIPK IKDNSGEIIATGTYDNKNKQITYTFTDYVDKYENIKAHLKLTSYIDKSKV PNNNTKLDVEYKTALSSVNKTITVEYQRPNENRTANLQSMFTNIDTKNHT VEQTIYINPLRYSAKETNVNISGNGDEGSTIIDDSTIIKVYKVGDNQNLP DSNRIYDYSEYEDVTNDDYAQLGNNNDVNINFGNIDSPYIIKVISKYDPN KDDYTTIQQTVTMQTTINEYTGEFRTASYDNTIAFSTSSGQGQGDLPPEK TYKIGDYVWEDVDKDGIQNTNDNEKPLSNVLVTLTYPDGTSKSVRTDEDG KYQFDGLKNGLTYKITFETPEGYTPTLKHSGTNPALDSEGNSVWVTINGQ DDMTIDSGFYQTPKYSLGNYVWYDTNKDGIQGDDEKGISGVKVTLKDENG NIISTTTTDENGKYQFDNLNSGNYIVHFDKPSGMTQTTTDSGDDDEQDAD GEEVHVTITDHDDFSIDNGYYDDE

EbhA and EbhB

[0068] EbhA and EbhB are proteins that are expressed in both S. aureus and S. epidermidis (Clarke and Foster Infect. Immun. 2002, 70; 6680, Williams et al Infect. Immun. 2002, 20; 6805) and which bind to fibronectin. Since fibronectin is an important component of extracellular matrix, EbhA and EbhB have an important function in adhering staphylococci to host extracellular matrix.

[0069] The Ebh proteins are large, having a molecular weight of 1.1 megadaltons. It is advantageous to use a fragment of the Ebh protein rather than the complete sequence due to ease of production and formulation. The central region of the protein contains imperfect repeats which contain fibronectin binding sites. Fragments containing one or more of the repeat domains described below are preferred fragments for incorporation into the immunogenic composition of the invention.

[0070] Ebh proteins contain imperfect repeats units of 127 amino acids in length which are characterised by containing the consensus sequence:-- [0071] L.G.{10}A.{13}Q.{26}L . . . M . . L.{33}A

[0072] Preferably [0073] .{19}L.G.{10}A.{13}Q.{26}L . . . M . . L.{33}A.{12}

[0074] More preferably [0075] . . . . . I/V . . A . . . I/V . . AK.ALN/DG . . NL . . AK . . A.{6}L . . LN.AQK . . L. . QI/V . . A . . V . . V.{6}A . . LN/D.AM . . L . . . I/V.D/E . . . TK.S.NY/F.N/DAD . . K . . AY/F . . AV . . A . . I/V.N/D . . . . . . .

[0076] Where `.` means any amino acid and `.{10}` means any 10 amino acids and I/V indicates alternative choices of amino acid.

[0077] By reference to the sequence disclosed in Kuroda et al (2001) Lancet 357; 1225-1240, and Table 2, the repeat sequences within Ebh proteins are readily deduced.

[0078] Preferred fragments to be included in the immunogenic composition of the invention include polypeptides containing of one, two, three, four, five, six, seven, eight, nine, ten or more than 10 of the 127 amino acid repeat units. Such fragments may consist of 1, 2, 3, 4, 5, 6, 7, 8, 9, or more repeats of the 127 amino acid repeat region or may consist of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more repeats with additional amino acid residues present at either or both ends of the fragment. A further preferred fragment is the H2 polypeptide of about 44 kDa spanning three repeats (amino acids 3202-3595) as described in Clarke et al Infection and Immunity 70, 6680-6687, 2002. Such fragments will preferably be able to bind fibronectin and/or to elicit antibodies that are reactive against the whole Ebh protein.

[0079] The Ebh polypeptides are capable of binding to fibronectin. Preferred fragments of these polypeptides sequences retain the ability to bind to fibronectin. Binding to fibronectin can be assessed by ELISA as described by Clarke et al (Infection and Immunity 70; 6680-6687 2002).

[0080] Still further preferred fragments are those which comprise a B-cell or T-helper epitope, for example those fragments/peptides described in Tables 3 and 4. TABLE-US-00003 TABLE 2 Repeat sequences in the full-length sequence of Ebh. The full-length sequence of Ebh is disclosed in Kuroda et al (2001) Lancet 357; 1225-1240. The following table shows the amino acid residues at which the 127 amino acid repeats begin and end within the full length sequence. Begin End 1 3204 3330 2 3331 3457 3 3457 3583 4 3583 3709 5 3709 3835 6 3835 3961 7 3961 4087 8 4200 4326 9 4326 4452 10 4452 4578 11 4578 4704 12 4704 4830 13 4830 4956 14 4956 5082 15 5082 5208 16 5208 5334 17 5334 5460 18 5460 5586 19 5585 5711 20 5711 5837 21 5837 5963 22 5963 6089 23 6089 6215 24 6215 6341 25 6341 6467 26 6467 6593 27 6593 6719 28 6719 6845 29 6845 6971 30 6971 7097 31 7097 7223 32 7223 7349 33 7349 7475 34 7475 7601 35 7601 7727 36 7727 7853 37 7852 7978 38 7978 8104 39 8104 8230 40 8230 8356 41 8356 8482 42 8482 8608 43 8604 8730 44 8858 8984

[0081] TABLE-US-00004 TABLE 3 B-cell epitope prediction for a 127 amino acid repeat: The full-length sequence is disclosed in Kuroda et al (2001) Lancet 357; 1225-1240. One of these repeats, encoded by amino acids 3204-3331 of the full-length sequence was chosen to carry out an epitope prediction:- MDVNTVNQKAASVKSTKDALDGQQNLQRAKTEATNAITHASDLNQAQKNA LTQQVNSAQNVHAVNDIKQTTQSLNTAMTGLKRGVANHNQVVQSDNYVNA DTNKKNDYNNAYNHANDIINGNAQHPVI Begin End Epitope sequence Start Stop 5 10 TVNQKA 3208 3213 14 19 KSTKDA 3217 3222 21 33 DGQQNLQRAKTEA 3224 3236 42 51 DLNQAQKNAL 3245 3254 66 74 DIKQTTQSL 3269 3277 100 112 ADTNKKNDYNNAY 3303 3315 117 123 DIINGNA 3320 3326 The "Begin" and "End" columns present the position of the predicted B-cell epitopes in the 127 amino acid repeat The "Start" and "Stop" columns present the position of the predicted B-cell epitopes in the Ebh full length sequence

[0082] TABLE-US-00005 TABLE 4 T-helper cell epitope prediction in Ebh: The full-length sequence is disclosed in TrEMBL database, sequence reference Q8NWQ6. One of these repeats, encoded by amino acids 3204-3331 of the full-length sequence was chosen to carry out an epitope prediction:- MDVNTVNQKAASVKSTKDALDGQQNTLQRAKTEATNAITHASDLNQAQKN ALTQQVNSAQNVHAVNDIKQTTQSLNTAMTGLKRGVANHNQVVQSDNYYN ADTNKKNDYNNAYNHANDIINGNAQHPVI Position Position repeat Epitope sequence sequence 1 MDVNTVNQK 3204 3 VNTVNQKAA 3206 6 VNQKAASVK 3209 26 LQRAKTEAT 3229 37 ITHASDLNQ 3240 43 LNQAQKNAL 3246 51 LTQQVNSAQ 3254 55 VNSAQNVHA 3258 61 VHAVNDIKQ 3264 64 VNDIKQTTQ 3267 67 IKQTTQSLN 3270 74 LNTAMTGLK 3277 78 MTGLKRGVA 3281 81 LKRGVANHN 3284 85 VANHNQVVQ 3288 91 VVQSDNYVN 3294 92 VQSDNYVNA 3295 97 YVNADTNKK 3301 98 VNADTNKKN 3302 108 YNNAYNHAN 3311 112 YNHANDIIN 3315 118 IINGNAQHP 3321 119 INGNAQHPV 3322 The "Position repeat" column presents the position of the predicted T-cell epitopes in the repeat The "Position sequence" column presents the position of the predicted T-cell epitopes in the Ebh full length sequence

[0083] Fragments of the polypeptides of the invention may be employed for producing the corresponding full-length polypeptide by peptide synthesis; therefore, these fragments may be employed as intermediates for producing the full-length polypeptides of the invention.

[0084] Particularly preferred are variants in which several, 5-10, 1-5, 1-3, 1-2 or 1 amino acids are substituted, deleted, or added in any combination.

Elastin Binding Protein (EbpS)

[0085] EbpS is a protein containing 486 amino acids with a molecular weight of 83 kDa. It is associated with the cytoplasmic membrane of S. aureus and has three hydrophobic regions which hold the protein in the membrane (Downer et al 2002, J. Biol. Chem. 277; 243; Park et al 1996, J. Biol. Chem. 271; 15803).

[0086] Two region between amino acids 1-205 and 343-486 are surface exposed on the outer face of the cytoplasmic membrane. The ligand binding domain of EbpS is located between residues 14-34 at the N-terminus (Park et al 1999, J. Biol. Chem. 274; 2845).

[0087] A preferred fragment to be incorporated into the immunogenic composition of the invention would be the surface exposed fragment containing the elastin binding region (amino acids 1-205). Some preferred fragments do not contain the entire exposed loop but should contain the elastin binding region (amino acids 14-34). An alternative fragment which could be used consists of amino acids forming the second surface exposed loop (amino acids 343-486). Alternative fragments containing up to 1, 2, 5, 10, 20, 50 amino acids less at one or both ends are also possible.

Laminin Receptors

[0088] The laminin receptor of S. aureus plays an important role in pathogenicity. A characteristic feature of infection is bloodstream invasion which allows widespread metastatic abscess formation. Bloodstream invasion requires the ability to extravasate across the vascular basement membrane. This is achieved through binding to laminin through the laminin receptor (Lopes et al Science 1985, 229; 275).

[0089] Laminin receptors are surface exposed and are present in many strains of staphylococci including S. aureus and S. epidermidis.

SBI

[0090] Sbi is a protein having an IgG binding region and an apolipoprotein H binding domain and it is expressed in most strains of S. aureus (Zhang et al 1998, Microbiology 144; 985).

[0091] The N-terminus of the sequence of Sbi has a typical signal sequence with a cleavage site after amino acid 29. Therefore a preferred fragment of Sbi to be incorporated into an immunogenic composition of the invention starts at amino acid residue 30, 31, 32 or 33 and continues to the C-terminus of Sbi, for example of SEQ ID NO: 26.

[0092] The IgG binding domain of Sbi has been identified as a region towards the N-terminus of the protein from amino acids 41-92. This domain is homologous to the IgG binding domains of protein A.

[0093] The minimal IgG binding domain of Sbi contains the following sequence:-- TABLE-US-00006 QTTQNNYVTDQQKAFYQVLHLKGITEEQRNQYIKTLREHPERAQEVFSES ** *** * *** * * * * LK * *-denotes amino acids which are similar between IgG binding domains

[0094] Preferred fragment of Sbi to be included in the immunogenic composition of the invention contains an IgG binding domain. This fragment contains the consensus sequence for an IgG binding domain as designated by * as shown in the above sequence. Preferably the fragment contains or consists of the complete sequence shown above. More preferably, the fragment contains or consists of amino acids 30-92, 33-92, 30-94, 33-94, 30-146, 33-146, 30-150, 33-150, 30-160, 33-160, 33-170, 33-180, 33-190, 33-200, 33-205 or 33-210 of Sbi, for example of SEQ ID NO:26.

[0095] Preferred fragment may contain 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 amino acid substitutions from the sequences indicated.

[0096] Preferred fragments may contain multiple repeats (2, 3, 4, 5, 6, 7, 8, 9 or 10) of the IgG binding domain.

EFB-FIB

[0097] Fib is a 19 kDa fibrinogen binding protein which is secreted into the extracellular medium by S. aureus. It is produced by all S aureus isolates tested (Wastfelt and Flock 1995, J. Clin. Microbiol. 33; 2347).

[0098] S. aureus clumps in the presence of fibrinogen and binds to fibrinogen coated surfaces. This ability facilitates staphylococcal colonisation of catheters and endothelial cells.

[0099] Fib contains a signal sequence at the N-terminus of the protein with a putative cleavage site at about amino acid 30. Therefore a preferred fragment to be introduced in the immunogenic composition of the invention would contain the sequence of the mature protein (from about amino acid 30 to the C-terminus of the protein).

IsaA/PisA

[0100] IsaA is a 29 kDa protein, also known as PisA has been shown to be a immunodominant staphylococcal protein during sepsis in hospital patients (Lorenz et al 2000, FEMS Immunol. Med. Microb. 29; 145).

[0101] The first 29 amino acids of the IsaA sequence are thought to be a signal sequence. Therefore a preferred fragment of IsaA to be included in an immunogenic composition of the invention would contain amino acid residues 30 onwards, to the end of the coded sequence.

Fibronectin Binding Protein

[0102] Fibronectin binding protein A (FnbA) is described in U.S. Pat. No. 5,320,951 and Schennings et al (1993, Microb. Pathog. 15; 227). Fibronectin binding protein A contains several domains that are involved in binding to fibronectin (WO 94/18327). These are called D1, D2, D3 and D4. Preferred fragments of fibronectin binding protein A or B comprise or consist of D1, D2, D3, D4, D1-D2, D2-D3, D3-D4, D1-D3, D2-D4 or D1-D4 (as described in WO 94/18327).

[0103] Fibronectin binding protein contains a 36 amino acid signal sequence. For example: TABLE-US-00007 VKNNLRYGIRKHKLGAASVFLGTMIVVGMGQDKEAA

[0104] Optionally, the mature protein omitting this signal sequence is included in the immunogenic composition of the invention.

Transporter Proteins

[0105] The cell wall of Gram positive bacteria acts as a barrier preventing free diffusion of metabolites into the bacterium. A family of proteins orchestrates the passage of essential nutrients into the bacterium and are therefore essential for the viability of the bacterium. The term transporter protein covers proteins involved in the initial step of binding to metabolites such as iron as well as those involved in actually transporting the metabolite into the bacterium.

[0106] Molecular iron is an essential co-factor for bacterial growth. Siderophores are secreted that bind free iron and then are captured by bacterial surface receptors that deliver iron for transport across the cytoplasmic membrane. Iron acquisition is critical for the establishment of human infections so that the generation of an immune response against this class of proteins leads to a loss of staphylococcal viability.

[0107] Examples of transporter proteins include Immunodominant ABC transporter (Burnie et al 2000 Infect. Imun. 68; 3200), IsdA (Mazmanian et al 2002 PNAS 99; 2293), IsdB (Mazmanian et al 2002 PNAS 99; 2293), Mg2+ transporter, SitC (Wiltshire and Foster 2001 Infect. Immun. 69; 5198) and Ni ABC transporter.

Immunodominant ABC Transporter

[0108] Immunodominant ABC transporter is a well conserved protein which may be capable of generating an immune response that is cross-protective against different staphylococcal strains (Mei et al 1997, Mol. Microbiol. 26; 399). Antibodies against this protein have been found in patients with septicaemia (Burnie et al 2000, Infect. Immun. 68; 3200).

[0109] Preferred fragments of immunodominant ABC transporter will include the peptides DRHFLN, GNYD, RRYPF, KTTLLK, GVTTSLS, VDWLR, RGFL, more preferably KIKVYVGNYDFWYQS, TVIVVSHDRHFLYNNV and/or TETFLRGFLGRMLFS since these sequences contain epitopes that are recognised by the human immune system.

IsdA-IsdB

[0110] The isd genes (iron-regulated surface determinant) of S. aureus encode proteins responsible for haemoglobin binding and passage of haem iron to the cytoplasm, where it acts as an essential nutrient. IsdA and IsdB are located in the cell wall of staphylococci. IsdA appear to be exposed on the surface of bacterium since it is susceptible to proteinase K digestion. IsdB was partially digested suggesting that it is partially exposed on the surface of the bacterium (Mazmanian et al 2003 Science 299; 906).

[0111] IsdA and IsdB are both 29 kDa proteins which bind heme. Their expression is regulated by the availability of iron via the Fur repressor. Their expression will be high during infection in a host where the concentration of iron will be low.

[0112] They are also known as FrpA and FrpB (Morrissey et al 2002, Infect. Immun. 70; 2399). FrpA and FrpB are major surface proteins with a high charge. They have been shown to provide a major contribution to adhesion to plastic.

[0113] In an embodiment, the immunogenic composition of the invention comprises a fragment of IsdA and/or IsdB which is described in WO 01/98499 or WO 03/11899.

Toxins and Regulators of Virulence

[0114] Members of this family of proteins include toxin such as alpha toxin, hemolysin, enterotoxin B and TSST-1 as well as proteins that regulate the production of toxins such as RAP.

Alpha Toxin (Hla)

[0115] Alpha toxin is an important virulence determinant produced by most strains of S. aureus. It is a pore forming toxin with haemolytic activity. Antibodies against alpha toxin have been shown to neutralise the detrimental and lethal effects of alpha toxin in animal models (Adlam et al 1977 Infect. Immun. 17; 250). Human platelets, endothelial cells and mononuclear cells are susceptible to the effects of alpha toxin.

[0116] The high toxicity of alpha toxin requires that it should be detoxified before being used as an immunogen. This can be achieved by chemical treatment, for instance by treating with formaldehyde, glutaraldehyde of other cross-linking reagents or by chemically conjugating it to bacterial polysaccharides as described below.

[0117] A further way of removing toxicity is to introduce point mutations that remove toxicity while retaining the antigenicity of the toxin. The introduction of a point mutation at amino acid 35 of alpha toxin where a histidine residue is replaced with a leucine residue results in the removal of toxicity whilst retaining immunogenicity (Menzies and Kernodle 1996; Infect. Immun. 64; 1839). Histidine 35 appears to be critical for the proper oligomerization required for pore formation and mutation of this residue leads to loss of toxicity.

[0118] When incorporated into immunogenic compositions of the invention, alpha toxin is preferably detoxified by mutation of His 35, most preferably by replacing His 35 with Leu or Arg. In an alternative embodiment, alpha toxin is detoxified by conjugation to other components of the immunogenic composition, preferably capsular polysaccharides, most preferably to S. aureus type V polysaccharide and/or S. aureus Type VIII polysaccharide and/or PNAG.

RNA III Activating Protein (RAP)

[0119] RAP is not itself a toxin, but is a regulator of the expression of virulence factors. RAP is produced and secreted by staphylococci. It activates the agr regulatory system of other staphylococci and activates the expression and subsequent release of virulence factors such as hemolysin, enterotoxin B and TSST-1.

[0120] An immune response generated against RAP would not kill the bacterium but would interfere with their pathogenicity. This has the advantage of providing less selective pressure for new resistant strains to emerge.

[0121] It would have a second advantage of producing an immune response that would be instrumental in reducing the morbidity of the infection.

[0122] It is particularly advantageous to combine RAP with other antigens in a vaccine, particularly where the additional antigen would provide an immune response that is able to kill the bacterium.

Other Proteins

Accumulation-Associated Protein (Aap)

[0123] Aap is a 140 kDa protein which is essential for the accumulation of S. epidermidis strains on surfaces (Hussain et al Infect. Immun. 1997, 65; 519). Strains expressing this protein produced significantly larger amounts of biofilm and Aap appear to be involved in biofilm formation. Antibodies against Aap are able to inhibit biofilm formation and inhibit the accumulation of S. epidermidis.

[0124] A preferred fragment of Aap is a conserved domain comprising or consisting of amino acids 550-1069.

Staphylococcal Secretory Antigen SsaA

[0125] SsaA is a strongly immunogenic protein of 30 kDa found in both S. aureus and S. epidermidis (Lang et al 2000 FEMS Immunol. Med. Microbiol. 29; 213). Its expression during endocarditis suggested a virulence role specific to the pathogenesis of the infectious disease.

[0126] SsaA contains an N-terminal leader sequence and a signal peptidase cleavage site. The leader peptide is followed by a hydrophilic region of approximately 100 amino acids from residue 30 to residue 130.

[0127] A preferred fragment of SsaA to be incorporated into the immunogenic composition of the invention is made up of the mature protein (amino acids 27 to the C-terminus or amino acids 30 to the C-terminus).

[0128] A further preferred fragments contains the hydrophilic area of SsaA from amino acid 30 to amino acid 130.

Preferred Combinations

[0129] A preferred combination of proteins in the immunogenic composition of the invention comprises laminin receptor and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0130] A further preferred combination of proteins in the immunogenic composition of the invention comprises SitC and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0131] A further preferred combination of proteins in the immunogenic composition of the invention comprises EbhA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0132] A further preferred combination of proteins in the immunogenic composition of the invention comprises EbhB and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0133] A further preferred combination of proteins in the immunogenic composition of the invention comprises EbpS and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0134] A further preferred combination of proteins in the immunogenic composition of the invention comprises EFB(FIB) and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0135] A further preferred combination of proteins in the immunogenic composition of the invention comprises SBI and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0136] A further preferred combination of proteins in the immunogenic composition of the invention comprises autolysin and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0137] A further preferred combination of proteins in the immunogenic composition of the invention comprises ClfA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0138] A further preferred combination of proteins in the immunogenic composition of the invention comprises SdrC and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0139] A further preferred combination of proteins in the immunogenic composition of the invention comprises SdrG and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant and RAP.

[0140] A further preferred combination of proteins in the immunogenic composition of the invention comprises SdrH and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0141] A further preferred combination of proteins in the immunogenic composition of the invention comprises Lipase GehD and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0142] A further preferred combination of proteins in the immunogenic composition of the invention comprises SasA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0143] A further preferred combination of proteins in the immunogenic composition of the invention comprises FnbA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0144] A further preferred combination of proteins in the immunogenic composition of the invention comprises FnbB and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0145] A further preferred combination of proteins in the immunogenic composition of the invention comprises Cna and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0146] A further preferred combination of proteins in the immunogenic composition of the invention comprises ClfB and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0147] A further preferred combination of proteins in the immunogenic composition of the invention comprises FbpA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0148] A further preferred combination of proteins in the immunogenic composition of the invention comprises Npase and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0149] A further preferred combination of proteins in the immunogenic composition of the invention comprises IsaA/PisA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0150] A further preferred combination of proteins in the immunogenic composition of the invention comprises SsaA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0151] A further preferred combination of proteins in the immunogenic composition of the invention comprises EPB and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0152] A further preferred combination of proteins in the immunogenic composition of the invention comprises SSP-1 and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0153] A further preferred combination of proteins in the immunogenic composition of the invention comprises SSP-2 and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0154] A further preferred combination of proteins in the immunogenic composition of the invention comprises HPB and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0155] A further preferred combination of proteins in the immunogenic composition of the invention comprises vitronectin binding protein and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0156] A further preferred combination of proteins in the immunogenic composition of the invention comprises fibrinogen binding protein and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0157] A further preferred combination of proteins in the immunogenic composition of the invention comprises coagulase and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0158] A further preferred combination of proteins in the immunogenic composition of the invention comprises Fig and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0159] A further preferred combination of proteins in the immunogenic composition of the invention comprises MAP and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0160] A further preferred combination of protein in the immunogenic composition of the invention comprises immunodominant ABC transporter and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0161] A further preferred combination of protein in the immunogenic composition of the invention comprises IsdA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0162] A further preferred combination of protein in the immunogenic composition of the invention comprises IsdB and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0163] A further preferred combination of protein in the immunogenic composition of the invention comprises SitC and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.

[0164] A further preferred combination of protein in the immunogenic composition of the invention comprises alpha toxin and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, Aap and SsaA.

[0165] A further preferred combination of protein in the immunogenic composition of the invention comprises alpha toxin H35L OR H35R variant and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, Aap and SsaA.

[0166] A further preferred combination of protein in the immunogenic composition of the invention comprises RAP and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, Aap and SsaA.

[0167] A further preferred combination of protein in the immunogenic composition of the invention comprises Aap and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, RAP, alpha toxin and H35L OR H35R alpha toxin.

[0168] A further preferred combination of protein in the immunogenic composition of the invention comprises SsaA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, RAP, alpha toxin and H35L OR H35R alpha toxin.

[0169] The inventors have demonstrated that certain antigens produce a particularly effective immune response within the context of a mixture of antigens. Accordingly, an embodiment of the invention is an immunogenic composition comprising IsaA and a staphylococcal transporter protein, or IsaA and a staphylococcal regulator of virulence or toxin, or comprising Sbi and a staphylococcal transporter protein, or Sbi and a staphylococcal regulator of virulence or toxin, or comprising SdrC and a staphylococcal transporter protein, or SdrC and a staphylococcal regulator of virulence or toxin, or IsaA and Sbi, or IsaA and SdrC, or IsaA and autolysin, or IsaA and Ebh, or Sbi and SdrC, or Sbi and Autolysin, or Sbi and Ebh, or SdrC and autolysin, or SdrC and Ebh, or Autolysin-glucosaminidase and Ebh. For each of these combinations, the proteins may be full length or fragments, having sequences at least 85%, 90%, 95%, 98% or 100% identical to that of the sequences of FIG. 1.

[0170] In the above and below combinations, the specified proteins may optionally be present in the immunogenic composition of the invention as a fragment or fusion protein as described above.

[0171] Preferred immunogenic compositions of the invention do not include the protein sequences disclosed in WO02/094868.

Combinations of Three Proteins

[0172] A preferred immunogenic composition of the invention contains three protein components in a combination of alpha-toxin, an extracellular component binding protein (preferably an adhesin) and a transporter protein (preferably an iron-binding protein).

[0173] In such a combination, the alpha toxin may be chemically detoxified or genetically detoxified by introduction of point mutation(s), preferably the His35Leu point mutation. The alpha toxin is present as a free protein or alternatively is conjugated to a polysaccharide or LTA component of the immunogenic composition.

Preferred combinations include:--

[0174] An immunogenic composition comprising alpha toxin, IsdA and an extracellular component binding protein selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig and MAP.

[0175] An immunogenic composition comprising alpha toxin, IsdB and an extracellular component binding protein selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig and MAP.

[0176] An immunogenic composition comprising alpha toxin, IsdA and an adhesin selected from the group consisting of laminin receptor, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), ClfA, SdrC, SdrG, SdrH, autolysin, FnbA, FnbB, Cna, ClfB, FbpA, Npase, SSP-1, SSP-2, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig and MAP.

[0177] An immunogenic composition comprising alpha toxin, IsdB and an adhesin selected from the group consisting of laminin receptor, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), autolysin, ClfA, SdrC, SdrG, SdrH, FnbA, FnbB, Cna, ClfB, FbpA, Npase, SSP-1, SSP-2, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig and MAP.

[0178] An immunogenic composition comprising alpha toxin, IsdA and laminin receptor.

[0179] An immunogenic composition comprising alpha toxin, IsdA and EbhA.

[0180] An immunogenic composition comprising alpha toxin, IsdA and EbhB.

[0181] An immunogenic composition comprising alpha toxin, IsdA and EbpS.

[0182] An immunogenic composition comprising alpha toxin, IsdA and EFB (FIB).

[0183] An immunogenic composition comprising alpha toxin, IsdA and SdrG.

[0184] An immunogenic composition comprising alpha toxin, IsdA and ClfA.

[0185] An immunogenic composition comprising alpha toxin, IsdA and ClfB.

[0186] An immunogenic composition comprising alpha toxin, IsdA and FnbA.

[0187] An immunogenic composition comprising alpha toxin, IsdA and coagulase.

[0188] An immunogenic composition comprising alpha toxin, IsdA and Fig.

[0189] An immunogenic composition comprising alpha toxin, IsdA and SdrH.

[0190] An immunogenic composition comprising alpha toxin, IsdA and SdrC.

[0191] An immunogenic composition comprising alpha toxin, IsdA and MAP.

[0192] An immunogenic composition comprising IsaA and Sbi.

[0193] An immunogenic composition comprising IsaA and IsdB.

[0194] An immunogenic composition comprising IsaA and IsdA.

[0195] An immunogenic composition comprising IsaA and SdrC.

[0196] An immunogenic composition comprising IsaA and Ebh or fragment thereof as described above.

[0197] An immunogenic composition comprising Sbi and SdrC.

[0198] An immunogenic composition comprising Sbi and Ebh or fragment thereof as described above.

[0199] An immunogenic composition of the invention comprising IsaA, Sbi or SdrC

Selection of Antigens Expressed in Different Clonal Lineages

[0200] Analysis of the occurrence of virulence factors in relation with the population structure of Staphylococcus aureus showed variable presence of virulence genes in natural populations of S. aureus.

[0201] Among clinical isolates of Staphylococcus aureus, at least five clonal lineages were shown to be highly prevalent (Booth et al., 2001 Infect Immun. 69 (1):345-52). Alpha-hemolysin (hla), fibronectin-binding protein A (fnbA) and clumping factor A (clfA) were shown to be present in most of the isolates, regardless of lineage identity, suggesting an important role of these proteins in the survival of S. aureus (Booth et al., 2001 Infect Immun. 69 (1):345-52). Moreover, according to Peacock et al. 2002 the distributions of fnbA, clfA, coagulase, spa, map, pvl (Panton-Valentine leukocidin), hlg (gamma-toxin), alpha-toxin and ica appeared to be unrelated to the underlying clonal structure suggesting considerable horizontal transfer of these genes.

[0202] In contrary, other virulence genes such as fibronectin binding protein B (fnbB), beta-hemolysin (hlb), collagen binding protein (cna), TSST-1 (tst) and methicillin resistance gene (mecA) are strongly associated with specific lineages (Booth et al., 2001 Infect Immun. 69 (1):345-52). Similarly, Peacock et al. 2002 (Infect Immun. 70 (9):4987-96) showed that the distributions of the enterotoxins, tst, the exfolatins (eta and etb), beta- and delta-toxins, the sdr genes (sdrD, sdrE and bbp), cna, ebpS and efb within the population are all highly significantly related to MLST-derived clonal complexes.

[0203] MLST data provide no evidence that strains responsible for nosocomial disease represent a distinct subpopulation from strains causing community-acquired disease or strains recovered from asymptomatic carriers (Feil et al., 2003 J Bacteriol. 185 (11):3307-16).

[0204] Preferred immunogenic compositions of the invention are effective against staphylococci from different clonal lineages.

[0205] In one embodiment, this is achieved by including 1, 2, 3, 4, preferably at least 1 protein that is expressed in most isolates of staphylococci. Examples of such proteins include alpha-hemolysin (hla), fibronectin-binding protein A (fnbA) and clumping factor A (clfA), coagulase, spa, map, pvl (Panton-Valentine leukocidin), hlg (gamma-toxin) and ica. We have also identified immunodominant ABC transporter, RAP, autolysin (Rupp et al 2001, J. Infect. Dis. 183; 1038), laminin receptors, SitC, IsaA/PisA, SPOIIIE O, SsaA, EbpS, SasF (Roche et al 2003, Microbiology 149; 643), EFB(FIB), SBI, ClfB, IsdA, IsdB, FnbB, Npase, EBP, Bone sialo binding protein II, IsaB/PisB (Lorenz et al FEMS Immuno. Med. Microb. 2000, 29; 145), SasH (Roche et al 2003, Microbiology 149; 643), MRPI, SasD (Roche et al 2003, Microbiology 149; 643), SasH (Roche et al 2003, Microbiology 149; 643), aureolysin precursor (AUR)/Sepp1 and novel autolysin.

[0206] In an alternative embodiment, 2 or more proteins which are expressed in different sets of clonal strains are included in the immunogenic composition of the invention. Preferably the combination of antigens will allow an immune response to be generated that is effective against multiple clonal strains, most preferably against all clonal stains. Preferred combinations include FnbB and betahemolysin, FnbB and Cna, FnbB and TSST-1, FnbB and mecA, FnbB and SdrD, FnbB and SdrF, FnbB and EbpS, FnbB and Efb, beta-haemolysin and Cna, beta-haemolysin and TSST-1, beta-haemolysin and mecA, beta-haemolysin and SdrD, beta-haemolysin and SdrF, beta-haemolysin and EbpS, beta-haemolysin and Efb, Cna and TSST-1, Cna and mecA, Cna and SdrD, Cna and SdrF, Cna and EbpS, Cna and Efb, TSST-1 and mecA, TSST-1 and SdrD, TSST-1 and SdrF, TSST-1 and EbpS, TssT-1 and Efb, MecA and SdrD, MecA and SdrF, MecA and EbpS, MecA and Efb, SdrD and SdrF, SdrD and EbpS, SdeD and Efb, SdrF and EbpS, SdrF and Efb, and, EbpS and Efb.

[0207] The preferred combinations described above may be combined with additional components described below.

Selection of Antigens Expressed During Different Growth Phases

[0208] Staphylococci go though an exponential growth phase during which a particular set of proteins will be expressed. These include many of the extracellular component binding proteins and transporter proteins. After a period of exponential growth, the staphylococci revert to a post-exponential phase during which growth is slower and protein expression is modulated. Many of the proteins expressed during the exponential growth phase are down regulated whereas other proteins, such as enzymes and most toxins, including alpha toxin, are expressed at higher levels.

[0209] Preferred immunogenic compositions of the invention comprise a protein expressed at higher levels during the exponential growth phase and a protein expressed at higher levels during the post-exponential phase.

[0210] `Higher levels` refers to the level of expression being higher in one phase in comparison with the other phase.

[0211] In a preferred embodiment, the immunogenic composition of the invention comprises alpha toxin and an extracellular component binding protein (preferably FnbA, FnbB, ClfA and ClfB) or a transporter protein.

[0212] More preferably it comprises alpha toxin or Cna or Lipase GehD and a protein selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, SasA, FnbA, FnbB, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig and MAP, Immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, Aap and SsaA.

[0213] In the combinations described above, the alpha toxin may be genetically or chemically detoxified as described above and may be unconjugated or conjugated to polysaccharide as described below.

Polysaccharides

[0214] The immunogenic compositions of the invention preferably further comprise capsular polysaccharides including one or more of PIA (also known as PNAG) and/or S. aureus Type V and/or type VIII capsular polysaccharide and/or S. epidermidis Type I, and/or Type II and/or Type III capsular polysaccharide.

PIA (PNAG)

[0215] It is now clear that the various forms of staphylococcal surface polysaccharides identified as PS/A, PIA and SAA are the same chemical entity--PNAG (Maira-Litran et al Vaccine 22; 872-879 (2004)). Therefore the term PIA or PNAG encompasses all these polysaccharides or oligosaccharides derived from them.

[0216] PIA is a polysaccharide intercellular adhesin and is composed of a polymer of .beta.-(1.fwdarw.6)-linked glucosamine substituted with N-acetyl and O-succinyl constituents. This polysaccharide is present in both S. aureus and S. epidermidis and can be isolated from either source (Joyce et al 2003, Carbohydrate Research 338; 903; Maira-Litran et al 2002, Infect. Imun. 70; 4433). For example, PNAG may be isolated from S. aureus strain MN8m (WO 04/43407).

[0217] PIA isolated from S. epidermidis is a integral constituent of biofilm. It is responsible for mediating cell-cell adhesion and probably also functions to shield the growing colony from the host's immune response.

[0218] The polysaccharide previously known as poly-N-succinyl-.beta.-(1.fwdarw.6)-glucosamine (PNSG) was recently shown not to have the expected structure since the identification of N-succinylation was incorrect (Maira-Litran et al 2002, Infect. Imun. 70; 4433). Therefore the polysaccharide formally known as PNSG and now found to be PNAG is also encompassed by the term PIA.

[0219] PIA (or PNAG) may be of different sizes varying from over 400 kDa to between 75 and 400 kDa to between 10 and 75 kDa to oligosaccharides composed of up to 30 repeat units (of .beta.-(1.fwdarw.6)-linked glucosamine substituted with N-acetyl and O-succinyl constituents). Any size of PIA polysaccharide or oligosaccharide may be use in an immunogenic composition of the invention, however a size of over 40 kDa is preferred. Sizing may be achieved by any method known in the art, for instance by microfluidisation, ultrasonic irradiation or by chemical cleavage (WO 03/53462, EP497524, EP497525).

[0220] Preferred size ranges of PIA (PNAG) are 40-400 kDa, 40-300 kDa, 50-350 kDa, 60-300 kDa, 50-250 kDa and 60-200 kDa.

[0221] PIA (PNAG) can have different degree of acetylation due to substitution on the amino groups by acetate. PIA produced in vitro is almost fully substituted on amino groups (95-100%). Alternatively, a deacetylated PIA (PNAG) can be used having less than 60%, preferably less than 50%, 40%, 30%, 20%, 10% acetylation. Use of a deacetylated PIA (PNAG) is preferred since non-acetylated epitopes of PNAG are efficient at mediating opsonic killing of Gram positive bacteria, preferably S. aureus and/or S. epidermidis. Most preferably, the PIA (PNAG) has a size between 40 kDa and 300 kDa and is deacetylated so that less than 60%, 50%, 40%, 30% or 20% of amino groups are acetylated.

[0222] The term deacetylated PNAG (dPNAG) refers to a PNAG polysaccharide or oligosaccharide in which less than 60%, 50%, 40%, 30%, 20% or 10% of the amino agroups are acetylated.

[0223] In an embodiment, PNAG is a deaceylated to form dPNAG by chemically treating the native polysaccharide. For example, the native PNAG is treated with a basic solution such that the pH rises to above 10. For instance the PNAG is treated with 0.1-5M, 0.2-4M, 0.3-3M, 0.5-2M, 0.75-1.5M or 1M NaOH, KOH or NH.sub.4OH. Treatment is for at least 10 or 30 minutes, or 1, 2, 3, 4, 5, 10, 15 or 20 hours at a temperature of 20-100, 25-80, 30-60 or 30-50 or 35-45.degree. C. dPNAG may be prepared as described in WO 04/43405.

[0224] The polysaccharide(s) included in the immunogenic composition of the invention are preferably conjugated to a carrier protein as described below or alternatively unconjugated.

Type 5 and Type 8 Polysaccharides from S. aureus

[0225] Most strains of S. aureus that cause infection in man contain either Type 5 or Type 8 polysaccharides. Approximately 60% of human strains are Type 8 and approximately 30% are Type 5. The structures of Type 5 and Type 8 capsular polysaccharide antigens are described in Moreau et al Carbohydrate Res. 201; 285 (1990) and Fournier et al Infect. Immun. 45; 87 (1984). Both have FucNAcp in their repeat unit as well as ManNAcA which can be used to introduce a sulfhydryl group. The structures were reported as:

Type 5

[0226] .fwdarw.4)-.beta.-D-ManNAcA(3OAc)-(1.fwdarw.4)-.alpha.-L-FucNAc(- 1.fwdarw.3)-.beta.-D-FucNAc-(1.fwdarw. Type 8 [0227] 3)-.beta.-D-ManNAcA(4OAc)-(1.fwdarw.3)-.alpha.-L-FucNAc(1.fwdarw.3)-.beta- .-D-FucNAc-(1.fwdarw.

[0228] Recently (Jones Carbohydrate Research 340, 1097-1106 (2005)) NMR spectroscopy revised to structures to

Type 5

[0229] 4)-.beta.-D-ManNAcA-(1.fwdarw.4)-.alpha.-L-FucNAc(3OAc)-(1.fwdar- w.3)-.beta.-D-FucNAc-(1.fwdarw. Type 8 [0230] 3)-.beta.-D-ManNAcA(4OAc)-(1.fwdarw.3)-.alpha.-FucNAc(1.fwdarw.3)-.alpha.- -D-FucNAc(1.fwdarw.

[0231] Polysaccharides may be extracted from the appropriate strain of S. aureus using method well known to the skilled man, for instance as described in U.S. Pat. No. 6,294,177. For example, ATCC 12902 is a Type 5 S. aureus strain and ATCC 12605 is a Type 8 S. aureus strain.

[0232] Polysaccharides are of native size or alternatively may be sized, for instance by microfluidisation, ultrasonic irradiation or by chemical treatment. The invention also covers oligosaccharides derived from the type 5 and 8 polysaccharides from S. aureus.

[0233] The type 5 and 8 polysaccharides included in the immunogenic composition of the invention are preferably conjugated to a carrier protein as described below or are alternatively unconjugated.

[0234] The immunogenic compositions of the invention alternatively contains either type 5 or type 8 polysaccharide.

S. aureus 336 Antigen

[0235] In an embodiment, the immunogenic composition of the invention comprises the S. aureus 336 antigen described in U.S. Pat. No. 6,294,177.

[0236] The 336 antigen comprises .beta.-linked hexosamine, contains no O-acetyl groups and specifically binds to antibodies to S. aureus Type 336 deposited under ATCC 55804.

[0237] In an embodiment, the 336 antigen is a polysaccharide which is of native size or alternatively may be sized, for instance by microfluidisation, ultrasonic irradiation or by chemical treatment. The invention also covers oligosaccharides derived from the 336 antigen.

[0238] The 336 antigen, where included in the immunogenic composition of the invention is preferably conjugated to a carrier protein as described below or are alternatively unconjugated.

Type I, II and III Polysaccharides from S. epidermidis

[0239] Strains ATCC-31432, SE-360 and SE-10 of S. epidermidis are characteristic of three different capsular types, I, II and III respectively (Ichiman and Yoshida 1981, J. Appl. Bacteriol. 51; 229). Capsular polysaccharides extracted from each serotype of S. epidermidis constitute Type I, II and III polysaccharides. Polysaccharides may be extracted by several methods including the method described in U.S. Pat. No. 4,197,290 or as described in Ichiman et al 1991, J. Appl. Bacteriol. 71; 176.

[0240] In one embodiment of the invention, the immunogenic composition comprises type I and/or II and/or III polysaccharides or oligosaccharides from S. epidermidis.

[0241] Polysaccharides are of native size or alternatively may be sized, for instance by microfluidisation, ultrasonic irradiation or chemical cleavage. The invention also covers oligosaccharides extracted from S. epidermidis strains.

[0242] These polysaccharides are unconjugated or are preferably conjugated as described below.

Conjugation of Polysaccharides

[0243] Amongst the problems associated with the use of polysaccharides in vaccination, is the fact that polysaccharides per se are poor immunogens. Strategies, which have been designed to overcome this lack of immunogenicity, include the linking of the polysaccharide to large protein carriers, which provide bystander T-cell help. It is preferred that the polysaccharides utilised in the invention are linked to a protein carrier which provide bystander T-cell help. Examples of such carriers which may be conjugated to polysaccharide immunogens include the Diphtheria and Tetanus toxoids (DT, DT crm197 and TT respectively), Keyhole Limpet Haemocyanin (KLH), and the purified protein derivative of Tuberculin (PPD), Pseudomonas aeruginosa exoprotein A (rEPA), protein D from Haemophilus influenzae, pneumolysin or fragments of any of the above. Fragments suitable for use include fragments encompassing T-helper epitopes. In particular protein D fragment will preferably contain the N-terminal 1/3 of the protein. Protein D is an IgD-binding protein from Haemophilus influenzae (EP 0 594 610 B1) and is a potential immunogen.

[0244] In addition, staphylococcal proteins may be used as carrier protein in the polysaccharide conjugates of the invention. The staphylococcal proteins described below may be used as carrier protein; for example, laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, Immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter alpha toxin (Hla), alpha toxin H35R mutant, RNA III activating protein (RAP), or fragments thereof.

[0245] A new carrier protein that would be particularly advantageous to use in the context of a staphylococcal vaccine is staphylococcal alpha toxoid. The native form may be conjugated to a polysaccharide since the process of conjugation reduces toxicity. Preferably a genetically detoxified alpha toxin such as the His35Leu or His 35 Arg variants are used as carriers since residual toxicity is lower. Alternatively the alpha toxin is chemically detoxified by treatment with a cross-linking reagent, formaldehyde or glutaraldehyde. A genetically detoxified alpha toxin is optionally chemically detoxified, preferably by treatment with a cross-linking reagent, formaldehyde or glutaraldehyde to further reduce toxicity.

[0246] The polysaccharides may be linked to the carrier protein(s) by any known method (for example, by Likhite, U.S. Pat. No. 4,372,945 by Armor et al., U.S. Pat. No. 4,474,757, and Jennings et al., U.S. Pat. No. 4,356,170). Preferably, CDAP conjugation chemistry is carried out (see WO95/08348).

[0247] In CDAP, the cyanylating reagent 1-cyano-dimethylaminopyridinium tetrafluoroborate (CDAP) is preferably used for the synthesis of polysaccharide-protein conjugates. The cyanilation reaction can be performed under relatively mild conditions, which avoids hydrolysis of the alkaline sensitive polysaccharides. This synthesis allows direct coupling to a carrier protein.

[0248] The polysaccharide is solubilized in water or a saline solution. CDAP is dissolved in acetonitrile and added immediately to the polysaccharide solution. The CDAP reacts with the hydroxyl groups of the polysaccharide to form a cyanate ester. After the activation step, the carrier protein is added. Amino groups of lysine react with the activated polysaccharide to form an isourea covalent link. After the coupling reaction, a large excess of glycine is then added to quench residual activated functional groups. The product is then passed through a gel permeation column to remove unreacted carrier protein and residual reagents.

[0249] Conjugation preferably involves producing a direct linkage between the carrier protein and polysaccharide. Optionally a spacer (such as adipic dihydride (ADH)) may be introduced between the carrier protein and the polysaccharide.

Protection Against S. aureus and S. epidermidis

[0250] In a preferred embodiment of the invention the immunogenic composition provides an effective immune response against more than one strain of staphylococci, preferably against strains from both S. aureus and S. epidermidis. More preferably, a protective immune response is generated against type 5 and 8 serotypes of S. aureus. More preferably, a protective immune response is generated against multiple strains of S. epidermidis, for instance from strains of at least two of serotypes I, II and III of S. epidermidis.

[0251] One use of the immunogenic composition of the invention is to prevent nosocomial infections by inoculating prior to hospital treatment. At this stage, it is difficult to accurately predict which staphylococcal strains the patient will be exposed to. It is therefore advantageous to inoculate with a vaccine that is capable of generating an effective immune response against various strains of staphylococci.

[0252] An effective immune response is defined as an immune response that gives significant protection in a mouse challenge model or opsonophagocytosis assay as described in the examples. Significant protection in a mouse challenge model, for instance that of example 5, is defined as an increase in the LD50 in comparison with carrier inoculated mice of at least 10%, 20%, 50%, 100% or 200%. Significant protection in a cotton rat challenge model, for instance that of example 8, is defined as a decrease in the mean observed LogCFU/nose of at least 10%, 20%, 50%, 70% or 90%. The presence of opsonising antibodies is known to correlate with protection, therefore significant protection is indicated by a decrease in the bacterial count of at least 10%, 20%, 50%, 70% or 90% in an opsonophagocytosis assay, for instance that of example 7.

[0253] Several of the proteins including immunodominant ABC transporter, RNA III activating protein, Laminin receptors, SitC, IsaA/PisA, SsaA, EbhA/EbhB, EbpS and Aap are well conserved between S. aureus and S. epidermidis and example 8 shows that IsaA, ClfA, IsdB, SdrG, HarA, FnbpA and Sbi can generate a cross-reactive immune response (for example crossreactive between at least one S. aureus and at least one S. epidermidis strain). PIA is also well conserved between S. aureus and S. epidermidis and is capable of inducing a cross-protective immune response.

[0254] Therefore in a preferred embodiment, the immunogenic composition of the invention will comprise two, three or four of the above proteins, preferably further comprising PIA (PNAG).

Polynucleotide Vaccines

[0255] In a further aspect, the present invention relates to the use of the polynucleotides of FIG. 2 in the treatment, prevention or diagnosis of staphylococcal infection. Such polynucleotides include isolated polynucleotides comprising a nucleotide sequence encoding a polypeptide which has at least 70% identity, preferably at least 80% identity, more preferably at least 90% identity, yet more preferably at least 95% identity, to the amino acid sequence of FIG. 1, over the entire length of the sequence. In this regard, polypeptides which have at least 97% identity are highly preferred, whilst those with at least 98-99% identity are more highly preferred, and those with at least 99% identity are most highly preferred.

[0256] Further polynucleotides that find utility in the present invention include isolated polynucleotides comprising a nucleotide sequence that has at least 70% identity, preferably at least 80% identity, more preferably at least 90% identity, yet more preferably at least 95% identity, to a nucleotide sequence encoding a protein of the invention over the entire coding region. In this regard, polynucleotides which have at least 97% identity are highly preferred, whilst those with at least 98-99% identity are more highly preferred, and those with at least 99% identity are most highly preferred.

[0257] Other polynucleotides include isolated polynucleotides comprising a nucleotide sequence which has at least 70% identity, preferably at least 80% identity, more preferably at least 90% identity, yet more preferably at least 95% identity, to the sequences of FIG. 1. In this regard, polynucleotides which have at least 97% identity are highly preferred, whilst those with at least 98-99% identity are more highly preferred, and those with at least 99% identity are most highly preferred. Said polynucleotide can be inserted in a suitable plasmid or recombinant microorganism vector and used for immunisation (see for example Wolff et. al., Science 247:1465-1468 (1990); Corr et. al., J. Exp. Med. 184:1555-1560 (1996); Doe et. al., Proc. Natl. Acad. Sci. 93:8578-8583 (1996)).

[0258] The present invention also provides a nucleic acid encoding the aforementioned proteins of the present invention and their use in medicine. In a preferred embodiment isolated polynucleotides according to the invention may be single-stranded (coding or antisense) or double-stranded, and may be DNA (genomic, cDNA or synthetic) or RNA molecules. Additional coding or non-coding sequences may, but need not, be present within a polynucleotide of the present invention. In other related embodiments, the present invention provides polynucleotide variants having substantial identity to the sequences disclosed herein in FIG. 2; those comprising at least 70% sequence identity, preferably at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or higher, sequence identity compared to a polynucleotide sequence of this invention using the methods described herein, (e.g., BLAST analysis using standard parameters). In a related embodiment, the isolated polynucleotide of the invention will comprise a nucleotide sequence encoding a polypeptide that has at least 90%, preferably 95% and above, identity to the amino acid sequence of FIG. 1, over the entire length of a sequence of FIG. 1; or a nucleotide sequence complementary to said isolated polynucleotide.

[0259] The invention also contemplates the use of polynucleotides which are complementary to all the above described polynucleotides.

[0260] The invention also provides for the use of a fragment of a polynucleotide of the invention which when administered to a subject has the same immunogenic properties as a polynucleotide of FIG. 1.

[0261] The invention also provides for the use of a polynucleotide encoding an immunological fragment of a protein of FIG. 1 as hereinbefore defined. Also contemplated are the use of such fragments that have a level of immunogenic activity of at least about 50%, preferably at least about 70% and more preferably at least about 90% of the level of immunogenic activity of a polypeptide sequence encoded by a polynucleotide sequence set forth in FIG. 2.

[0262] Polypeptide fragments for use according to the invention preferably comprise at least about 5, 10, 15, 20, 25, 50, or 100 contiguous amino acids, or more, including all intermediate lengths, of a polypeptide composition set forth herein, such as those set forth above.

[0263] Polynucleotides for use in the invention may be obtained, using standard cloning and screening techniques, from a cDNA library derived from mRNA in cells of human preneoplasic or tumour tissue (lung for example), (for example Sambrook et al., Molecular Cloning: A Laboratory Manual, 2.sup.nd Ed., Cold Spring harbor Laboratory Press, Cold Spring harbor, N.Y. (1989)). Polynucleotides of the invention can also be obtained from natural sources such as genomic DNA libraries or can be synthesised using well-known and commercially available techniques.

[0264] There are several methods available and well known to those skilled in the art to obtain full-length cDNAs, or extend short cDNAs, for example those based on the method of Rapid Amplification of cDNA ends (RACE) (see, for example, Frohman et al., PNAS USA 85, 8998-9002, 1988). Recent modifications of the technique, exemplified by the Marathon.TM. technology (Clontech Laboratories Inc.) for example, have significantly simplified the search for longer cDNAs. In the Marathon.TM. technology, cDNAs have been prepared from mRNA extracted from a chosen tissue and an `adaptor` sequence ligated onto each end. Nucleic acid amplification (PCR) is then carried out to amplify the `missing` 5' end of the cDNA using a combination of gene specific and adaptor specific oligonucleotide primers. The PCR reaction is then repeated using `nested` primers, that is, primers designed to anneal within the amplified product (typically an adaptor specific primer that anneals further 3' in the adaptor sequence and a gene specific primer that anneals further 5' in the known gene sequence). The products of this reaction can then be analysed by DNA sequencing and a full-length cDNA constructed either by joining the product directly to the existing cDNA to give a complete sequence, or carrying out a separate full-length PCR using the new sequence information for the design of the 5' primer.

[0265] Vectors comprising such DNA, hosts transformed thereby and the truncated or hybrid proteins themselves, expressed as described hereinbelow all form part of the invention.

[0266] The expression system may also be a recombinant live microorganism, such as a virus or bacterium. The gene of interest can be inserted into the genome of a live recombinant virus or bacterium. Inoculation and in vivo infection with this live vector will lead to in vivo expression of the antigen and induction of immune responses.

[0267] Therefore, in certain embodiments, polynucleotides encoding immunogenic polypeptides for use according to the present invention are introduced into suitable mammalian host cells for expression using any of a number of known viral-based systems. In one illustrative embodiment, retroviruses provide a convenient and effective platform for gene delivery systems. A selected nucleotide sequence encoding a polypeptide for use in the present invention can be inserted into a vector and packaged in retroviral particles using techniques known in the art. The recombinant virus can then be isolated and delivered to a subject. A number of illustrative retroviral systems have been described (e.g., U.S. Pat. No. 5,219,740; Miller and Rosman (1989) BioTechniques 7:980-990; Miller, A. D. (1990) Human Gene Therapy 1:5-14; Scarpa et al. (1991) Virology 180:849-852; Burns et al. (1993) Proc. Natl. Acad. Sci. USA 90:8033-8037; and Boris-Lawrie and Temin (1993) Cur. Opin. Genet. Develop. 3:102-109.

[0268] In addition, a number of illustrative adenovirus-based systems have also been described. Unlike retroviruses which integrate into the host genome, adenoviruses persist extrachromosomally thus minimising the risks associated with insertional mutagenesis (Haj-Ahmad and Graham (1986) J. Virol. 57:267-274; Bett et al. (1993) J. Virol. 67:5911-5921; Mittereder et al. (1994) Human Gene Therapy 5:717-729; Seth et al. (1994) J. Virol. 68:933-940; Barr et al. (1994) Gene Therapy 1:51-58; Berkner, K. L. (1988) BioTechniques 6:616-629; and Rich et al. (1993) Human Gene Therapy 4:461-476).

[0269] Various adeno-associated virus (AAV) vector systems have also been developed for polynucleotide delivery. AAV vectors can be readily constructed using techniques well known in the art. See, e.g., U.S. Pat. Nos. 5,173,414 and 5,139,941; International Publication Nos. WO 92/01070 and WO 93/03769; Lebkowski et al. (1988) Molec. Cell. Biol. 8:3988-3996; Vincent et al. (1990) Vaccines 90 (Cold Spring Harbor Laboratory Press); Carter, B. J. (1992) Current Opinion in Biotechnology 3:533-539; Muzyczka, N. (1992) Current Topics in Microbiol. and Immunol. 158:97-129; Kotin, R. M. (1994) Human Gene Therapy 5:793-801; Shelling and Smith (1994) Gene Therapy 1:165-169; and Zhou et al. (1994) J. Exp. Med. 179:1867-1875.

[0270] Additional viral vectors useful for delivering the nucleic acid molecules encoding polypeptides for use in the present invention by gene transfer include those derived from the pox family of viruses, such as vaccinia virus and avian poxvirus. By way of example, vaccinia virus recombinants expressing the molecules of interest can be constructed as follows. The DNA encoding a polypeptide is first inserted into an appropriate vector so that it is adjacent to a vaccinia promoter and flanking vaccinia DNA sequences, such as the sequence encoding thymidine kinase (TK). This vector is then used to transfect cells which are simultaneously infected with vaccinia. Homologous recombination serves to insert the vaccinia promoter plus the gene encoding the polypeptide of interest into the viral genome. The resulting TK.sup.(-) recombinant can be selected by culturing the cells in the presence of 5-bromodeoxyuridine and picking viral plaques resistant thereto.

[0271] A vaccinia-based infection/transfection system can be conveniently used to provide for inducible, transient expression or coexpression of one or more polypeptides described herein in host cells of an organism. In this particular system, cells are first infected in vitro with a vaccinia virus recombinant that encodes the bacteriophage T7 RNA polymerase. This polymerase displays exquisite specificity in that it only transcribes templates bearing T7 promoters. Following infection, cells are transfected with the polynucleotide or polynucleotides of interest, driven by a T7 promoter. The polymerase expressed in the cytoplasm from the vaccinia virus recombinant transcribes the transfected DNA into RNA which is then translated into polypeptide by the host translational machinery. The method provides for high level, transient, cytoplasmic production of large quantities of RNA and its translation products. See, e.g., Elroy-Stein and Moss, Proc. Natl. Acad. Sci. USA (1990) 87:6743-6747; Fuerst et al. Proc. Natl. Acad. Sci. USA (1986) 83:8122-8126.

[0272] Alternatively, avipoxviruses, such as the fowlpox and canarypox viruses, can also be used to deliver the coding sequences of interest. Recombinant avipox viruses, expressing immunogens from mammalian pathogens, are known to confer protective immunity when administered to non-avian species. The use of an Avipox vector is particularly desirable in human and other mammalian species since members of the Avipox genus can only productively replicate in susceptible avian species and therefore are not infective in mammalian cells. Methods for producing recombinant Avipoxviruses are known in the art and employ genetic recombination, as described above with respect to the production of vaccinia viruses. See, e.g., WO 91/12882; WO 89/03429; and WO 92/03545.

[0273] Any of a number of alphavirus vectors can also be used for delivery of polynucleotide compositions for use in the present invention, such as those vectors described in U.S. Pat. Nos. 5,843,723; 6,015,686; 6,008,035 and 6,015,694. Certain vectors based on Venezuelan Equine Encephalitis (VEE) can also be used, illustrative examples of which can be found in U.S. Pat. Nos. 5,505,947 and 5,643,576.

[0274] Moreover, molecular conjugate vectors, such as the adenovirus chimeric vectors described in Michael et al. J. Biol. Chem. (1993) 268:6866-6869 and Wagner et al. Proc. Natl. Acad. Sci. USA (1992) 89:6099-6103, can also be used for gene delivery under the invention.

[0275] Additional illustrative information on these and other known viral-based delivery systems can be found, for example, in Fisher-Hoch et al., Proc. Natl. Acad. Sci. USA 86:317-321, 1989; Flexner et al., Ann. N.Y. Acad. Sci. 569:86-103, 1989; Flexner et al., Vaccine 8:17-21, 1990; U.S. Pat. Nos. 4,603,112, 4,769,330, and 5,017,487; WO 89/01973; U.S. Pat. No. 4,777,127; GB 2,200,651; EP 0,345,242; WO 91/02805; Berkner, Biotechniques 6:616-627, 1988; Rosenfeld et al., Science 252:431-434, 1991; Kolls et al., Proc. Natl. Acad. Sci. USA 91:215-219, 1994; Kass-Eisler et al., Proc. Natl. Acad. Sci. USA 90:11498-11502, 1993; Guzman et al., Circulation 88:2838-2848, 1993; and Guzman et al., Cir. Res. 73:1202-1207, 1993.

[0276] The recombinant live microorganisms described above can be virulent, or attenuated in various ways in order to obtain live vaccines. Such live vaccines also form part of the invention.

[0277] In certain embodiments, a polynucleotide may be integrated into the genome of a target cell. This integration may be in the specific location and orientation via homologous recombination (gene replacement) or it may be integrated in a random, non-specific location (gene augmentation). In yet further embodiments, the polynucleotide may be stably maintained in the cell as a separate, episomal segment of DNA. Such polynucleotide segments or "episomes" encode sequences sufficient to permit maintenance and replication independent of or in synchronization with the host cell cycle. The manner in which the expression construct is delivered to a cell and where in the cell the polynucleotide remains is dependent on the type of expression construct employed.

[0278] In another embodiment of the invention, a polynucleotide is administered/delivered as "naked" DNA, for example as described in Ulmer et al., Science 259:1745-1749, 1993 and reviewed by Cohen, Science 259:1691-1692, 1993. The uptake of naked DNA may be increased by coating the DNA onto biodegradable beads, which are efficiently transported into the cells.

[0279] In still another embodiment, a composition of the present invention can be delivered via a particle bombardment approach, many of which have been described. In one illustrative example, gas-driven particle acceleration can be achieved with devices such as those manufactured by Powderject Pharmaceuticals PLC (Oxford, UK) and Powderject Vaccines Inc. (Madison, Wis.), some examples of which are described in U.S. Pat. Nos. 5,846,796; 6,010,478; 5,865,796; 5,584,807; and EP Patent No. 0500 799. This approach offers a needle-free delivery approach wherein a dry powder formulation of microscopic particles, such as polynucleotide or polypeptide particles, are accelerated to high speed within a helium gas jet generated by a hand held device, propelling the particles into a target tissue of interest.

[0280] In a related embodiment, other devices and methods that may be useful for gas-driven needle-less injection of compositions of the present invention include those provided by Bioject, Inc. (Portland, Oreg.), some examples of which are described in U.S. Pat. Nos. 4,790,824; 5,064,413; 5,312,335; 5,383,851; 5,399,163; 5,520,639 and 5,993,412.

Vaccines

[0281] In a preferred embodiment, the immunogenic composition of the invention is mixed with a pharmaceutically acceptable excipient, more preferably with an adjuvant to form a vaccine.

[0282] The vaccines of the present invention are preferably adjuvanted. Suitable adjuvants include an aluminum salt such as aluminum hydroxide gel (alum) or aluminium phosphate, but may also be a salt of calcium, magnesium, iron or zinc, or may be an insoluble suspension of acylated tyrosine, or acylated sugars, cationically or anionically derivatized polysaccharides, or polyphosphazenes.

[0283] It is preferred that the adjuvant be selected to be a preferential inducer of either a TH1 or a TH2 type of response. High levels of Th1-type cytokines tend to favor the induction of cell mediated immune responses to a given antigen, whilst high levels of Th2-type cytokines tend to favour the induction of humoral immune responses to the antigen. It is important to remember that the distinction of Th1 and Th2-type immune response is not absolute. In reality an individual will support an immune response which is described as being predominantly Th1 or predominantly Th2. However, it is often convenient to consider the families of cytokines in terms of that described in murine CD4 +ve T cell clones by Mosmann and Coffman (Mosmann, T. R. and Coffman, R. L. (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annual Review of Immunology, 7, p 145-173). Traditionally, Th1-type responses are associated with the production of the INF-.gamma. and IL-2 cytokines by T-lymphocytes. Other cytokines often directly associated with the induction of Th1-type immune responses are not produced by T-cells, such as IL-12. In contrast, Th2-type responses are associated with the secretion of Il-4, IL-5, IL-6, IL-10. Suitable adjuvant systems which promote a predominantly Th1 response include: Monophosphoryl lipid A or a derivative thereof, particularly 3-de-O-acylated monophosphoryl lipid A (3D-MPL) (for its preparation see GB 2220211 A); and a combination of monophosphoryl lipid A, preferably 3-de-O-acylated monophosphoryl lipid A, together with either an aluminium salt (for instance aluminium phosphate or aluminium hydroxide) or an oil-in-water emulsion. In such combinations, antigen and 3D-MPL are contained in the same particulate structures, allowing for more efficient delivery of antigenic and immunostimulatory signals. Studies have shown that 3D-MPL is able to further enhance the immunogenicity of an alum-adsorbed antigen [Thoelen et al. Vaccine (1998) 16:708-14; EP 689454-B1].

[0284] An enhanced system involves the combination of a monophosphoryl lipid A and a saponin derivative, particularly the combination of QS21 and 3D-MPL as disclosed in WO 94/00153, or a less reactogenic composition where the QS21 is quenched with cholesterol as disclosed in WO 96/33739. A particularly potent adjuvant formulation involving QS21, 3D-MPL and tocopherol in an oil in water emulsion is described in WO 95/17210, and is a preferred formulation. Preferably the vaccine additionally comprises a saponin, more preferably QS21. The formulation may also comprise an oil in water emulsion and tocopherol (WO 95/17210). The present invention also provides a method for producing a vaccine formulation comprising mixing a protein of the present invention together with a pharmaceutically acceptable excipient, such as 3D-MPL. Unmethylated CpG containing oligonucleotides (WO 96/02555) are also preferential inducers of a TH1 response and are suitable for use in the present invention.

[0285] Preferred compositions of the invention are those forming a liposome structure. Compositions where the sterol/immunologically active saponin fraction forms an ISCOM structure also form an aspect of the invention.

[0286] The ratio of QS21:sterol will typically be in the order of 1:100 to 1:1 weight to weight. Preferably excess sterol is present, the ratio of QS21:sterol being at least 1:2 w/w. Typically for human administration QS21 and sterol will be present in a vaccine in the range of about 1 .mu.g to about 100 .mu.g, preferably about 10 .mu.g to about 50 .mu.g per dose.

[0287] The liposomes preferably contain a neutral lipid, for example phosphatidylcholine, which is preferably non-crystalline at room temperature, for example eggyolk phosphatidylcholine, dioleoyl phosphatidylcholine or dilauryl phosphatidylcholine. The liposomes may also contain a charged lipid which increases the stability of the liposome-QS21 structure for liposomes composed of saturated lipids. In these cases the amount of charged lipid is preferably 1-20% w/w, most preferably 5-10%. The ratio of sterol to phospholipid is 1-50% (mol/mol), most preferably 20-25%.

[0288] Preferably the compositions of the invention contain MPL (3-deacylated mono-phosphoryl lipid A, also known as 3D-MPL). 3D-MPL is known from GB 2 220 211 (Ribi) as a mixture of 3 types of De-O-acylated monophosphoryl lipid A with 4, 5 or 6 acylated chains and is manufactured by Ribi Immunochem, Montana. A preferred form is disclosed in International Patent Application 92/116556.

[0289] Suitable compositions of the invention are those wherein liposomes are initially prepared without MPL, and MPL is then added, preferably as 100 nm particles. The MPL is therefore not contained within the vesicle membrane (known as MPL out). Compositions where the MPL is contained within the vesicle membrane (known as MPL in) also form an aspect of the invention. The antigen can be contained within the vesicle membrane or contained outside the vesicle membrane. Preferably soluble antigens are outside and hydrophobic or lipidated antigens are either contained inside or outside the membrane.

[0290] The vaccine preparations of the present invention may be used to protect or treat a mammal susceptible to infection, by means of administering said vaccine via systemic or mucosal route. These administrations may include injection via the intramuscular, intraperitoneal, intradermal or subcutaneous routes; or via mucosal administration to the oral/alimentary, respiratory, genitourinary tracts. Intranasal administration of vaccines for the treatment of pneumonia or otitis media is preferred (as nasopharyngeal carriage of pneumococci can be more effectively prevented, thus attenuating infection at its earliest stage). Although the vaccine of the invention may be administered as a single dose, components thereof may also be co-administered together at the same time or at different times (for instance pneumococcal polysaccharides could be administered separately, at the same time or 1-2 weeks after the administration of any bacterial protein component of the vaccine for optimal coordination of the immune responses with respect to each other). For co-administration, the optional Th1 adjuvant may be present in any or all of the different administrations, however it is preferred if it is present in combination with the bacterial protein component of the vaccine. In addition to a single route of administration, 2 different routes of administration may be used. For example, polysaccharides may be administered IM (or ID) and bacterial proteins may be administered IN (or ID). In addition, the vaccines of the invention may be administered IM for priming doses and IN for booster doses.

[0291] The amount of conjugate antigen in each vaccine dose is selected as an amount which induces an immunoprotective response without significant, adverse side effects in typical vaccines. Such amount will vary depending upon which specific immunogen is employed and how it is presented. Generally, it is expected that each dose will comprise 0.1-100 .mu.g of polysaccharide, preferably 0.1-50 .mu.g for polysaccharide conjugates, preferably 0.1-10 .mu.g, more preferably 1-10 .mu.g, of which 1 to 5 .mu.g is a more preferable range.

[0292] The content of protein antigens in the vaccine will typically be in the range 1-100 .mu.g, preferably 5-50 .mu.g, most typically in the range 5-25 .mu.g. Following an initial vaccination, subjects may receive one or several booster immunizations adequately spaced.

[0293] Vaccine preparation is generally described in Vaccine Design ("The subunit and adjuvant approach" (eds Powell M. F. & Newman M. J.) (1995) Plenum Press New York). Encapsulation within liposomes is described by Fullerton, U.S. Pat. No. 4,235,877.

[0294] The vaccines of the present invention may be stored in solution or lyophilized. Preferably the solution is lyophilized in the presence of a sugar such as sucrose, trehalose or lactose. It is still further preferable that they are lyophilized and extemporaneously reconstituted prior to use. Lyophilizing may result in a more stable composition (vaccine) and may possibly lead to higher antibody titers in the presence of 3D-MPL and in the absence of an aluminium based adjuvant.

Antibodies and Passive Immunisation

[0295] Another aspect of the invention is a method of preparing an immune globulin for use in prevention or treatment of staphylococcal infection comprising the steps of immunising a recipient with the vaccine of the invention and isolating immune globulin from the recipient. An immune globulin prepared by this method is a further aspect of the invention. A pharmaceutical composition comprising the immune globulin of the invention and a pharmaceutically acceptable carrier is a further aspect of the invention which could be used in the manufacture of a medicament for the treatment or prevention of staphylococcal disease. A method for treatment or prevention of staphylococcal infection comprising a step of administering to a patient an effective amount of the pharmaceutical preparation of the invention is a further aspect of the invention.

[0296] Inocula for polyclonal antibody production are typically prepared by dispersing the antigenic composition in a physiologically tolerable diluent such as saline or other adjuvants suitable for human use to form an aqueous composition. An immunostimulatory amount of inoculum is administered to a mammal and the inoculated mammal is then maintained for a time sufficient for the antigenic composition to induce protective antibodies.

[0297] The antibodies can be isolated to the extent desired by well known techniques such as affinity chromatography (Harlow and Lane Antibodies; a laboratory manual 1988).

[0298] Antibodies can include antiserum preparations from a variety of commonly used animals e.g. goats, primates, donkeys, swine, horses, guinea pigs, rats or man. The animals are bled and serum recovered.

[0299] An immune globulin produced in accordance with the present invention can include whole antibodies, antibody fragments or subfragments. Antibodies can be whole immunoglobulins of any class e.g. IgG, IgM, IgA, IgD or IgE, chimeric antibodies or hybrid antibodies with dual specificity to two or more antigens of the invention. They may also be fragments e.g. F(ab')2, Fab', Fab, Fv and the like including hybrid fragments. An immune globulin also includes natural, synthetic or genetically engineered proteins that act like an antibody by binding to specific antigens to form a complex.

[0300] A vaccine of the present invention can be administered to a recipient who then acts as a source of immune globulin, produced in response to challenge from the specific vaccine. A subject thus treated would donate plasma from which hyperimmune globulin would be obtained via conventional plasma fractionation methodology. The hyperimmune globulin would be administered to another subject in order to impart resistance against or treat staphylococcal infection. Hyperimmune globulins of the invention are particularly useful for treatment or prevention of staphylococcal disease in infants, immune compromised individuals or where treatment is required and there is no time for the individual to produce antibodies in response to vaccination.

[0301] An additional aspect of the invention is a pharmaceutical composition comprising two of more monoclonal antibodies (or fragments thereof; preferably human or humanised) reactive against at least two constituents of the immunogenic composition of the invention, which could be used to treat or prevent infection by Gram positive bacteria, preferably staphylococci, more preferably S. aureus or S. epidermidis.

[0302] Such pharmaceutical compositions comprise monoclonal antibodies that can be whole immunoglobulins of any class e.g. IgG, IgM, IgA, IgD or IgE, chimeric antibodies or hybrid antibodies with specificity to two or more antigens of the invention. They may also be fragments e.g. F(ab')2, Fab', Fab, Fv and the like including hybrid fragments.

[0303] Methods of making monoclonal antibodies are well known in the art and can include the fusion of splenocytes with myeloma cells (Kohler and Milstein 1975 Nature 256; 495; Antibodies--a laboratory manual Harlow and Lane 1988). Alternatively, monoclonal Fv fragments can be obtained by screening a suitable phage display library (Vaughan T J et al 1998 Nature Biotechnology 16; 535). Monoclonal antibodies may be humanised or part humanised by known methods.

Methods

[0304] The invention also encompasses method of making the immunogenic compositions and vaccines of the invention.

[0305] A preferred process of the invention, is a method to make a vaccine comprising the steps of mixing antigens to make the immunogenic composition of the invention and adding a pharmaceutically acceptable excipient.

Methods of Treatment

[0306] The invention also encompasses method of treatment or staphylococcal infection, particularly hospital acquired nosocomial infections.

[0307] This immunogenic composition or vaccine of the invention is particularly advantageous to use in cases of elective surgery. Such patients will know the date of surgery in advance and could be inoculated in advance. Since it is not know whether the patient will be exposed to S. aureus or S. epidermidis infection, it is preferred to inoculate with a vaccine of the invention that protects against both, as described above. Preferably adults over 16 awaiting elective surgery are treated with the immunogenic compositions and vaccines of the invention.

[0308] It is also advantageous to inoculate health care workers with the vaccine of the invention.

[0309] The vaccine preparations of the present invention may be used to protect or treat a mammal susceptible to infection, by means of administering said vaccine via systemic or mucosal route. These administrations may include injection via the intramuscular, intraperitoneal, intradermal or subcutaneous routes; or via mucosal administration to the oral/alimentary, respiratory, genitourinary tracts.

[0310] The amount of antigen in each vaccine dose is selected as an amount which induces an immunoprotective response without significant, adverse side effects in typical vaccines. Such amount will vary depending upon which specific immunogen is employed and how it is presented. The protein content of the vaccine will typically be in the range 1-100 .mu.g, preferably 5-50 .mu.g, most typically in the range 10-25 .mu.g. Generally, it is expected that each dose will comprise 0.1-100 .mu.g of polysaccharide where present, preferably 0.1-50 .mu.g, preferably 0.1-10 .mu.g, of which 1 to 5 .mu.g is the most preferable range. An optimal amount for a particular vaccine can be ascertained by standard studies involving observation of appropriate immune responses in subjects. Following an initial vaccination, subjects may receive one or several booster immunisations adequately spaced.

[0311] Although the vaccines of the present invention may be administered by any route, administration of the described vaccines into the skin (ID) forms one embodiment of the present invention. Human skin comprises an outer "horny" cuticle, called the stratum corneum, which overlays the epidermis. Underneath this epidermis is a layer called the dermis, which in turn overlays the subcutaneous tissue. Researchers have shown that injection of a vaccine into the skin, and in particular the dermis, stimulates an immune response, which may also be associated with a number of additional advantages. Intradermal vaccination with the vaccines described herein forms a preferred feature of the present invention.

[0312] The conventional technique of intradermal injection, the "mantoux procedure", comprises steps of cleaning the skin, and then stretching with one hand, and with the bevel of a narrow gauge needle (26-31 gauge) facing upwards the needle is inserted at an angle of between 10-15.degree.. Once the bevel of the needle is inserted, the barrel of the needle is lowered and further advanced whilst providing a slight pressure to elevate it under the skin. The liquid is then injected very slowly thereby forming a bleb or bump on the skin surface, followed by slow withdrawal of the needle.

[0313] More recently, devices that are specifically designed to administer liquid agents into or across the skin have been described, for example the devices described in WO 99/34850 and EP 1092444, also the jet injection devices described for example in WO 01/13977; U.S. Pat. No. 5,480,381, U.S. Pat. No. 5,599,302, U.S. Pat. No. 5,334,144, U.S. Pat. No. 5,993,412, U.S. Pat. No. 5,649,912, U.S. Pat. No. 5,569,189, U.S. Pat. No. 5,704,911, U.S. Pat. No. 5,383,851, U.S. Pat. No. 5,893,397, U.S. Pat. No. 5,466,220, U.S. Pat. No. 5,339,163, U.S. Pat. No. 5,312,335, U.S. Pat. No. 5,503,627, U.S. Pat. No. 5,064,413, U.S. Pat. No. 5,520,639, U.S. Pat. No. 4,596,556, U.S. Pat. No. 4,790,824, U.S. Pat. No. 4,941,880, U.S. Pat. No. 4,940,460, WO 97/37705 and WO 97/13537. Alternative methods of intradermal administration of the vaccine preparations may include conventional syringes and needles, or devices designed for ballistic delivery of solid vaccines (WO 99/27961), or transdermal patches (WO 97/48440; WO 98/28037); or applied to the surface of the skin (transdermal or transcutaneous delivery WO 98/20734; WO 98/28037).

[0314] When the vaccines of the present invention are to be administered to the skin, or more specifically into the dermis, the vaccine is in a low liquid volume, particularly a volume of between about 0.05 ml and 0.2 ml.

[0315] The content of antigens in the skin or intradermal vaccines of the present invention may be similar to conventional doses as found in intramuscular vaccines (see above). However, it is a feature of skin or intradermal vaccines that the formulations may be "low dose". Accordingly the protein antigens in "low dose" vaccines are preferably present in as little as 0.1 to 10 .mu.g, preferably 0.1 to 5 .mu.g per dose; and the polysaccharide (preferably conjugated) antigens may be present in the range of 0.01-1 .mu.g, and preferably between 0.01 to 0.5 .mu.g of polysaccharide per dose.

[0316] As used herein, the term "intradermal delivery" means delivery of the vaccine to the region of the dermis in the skin. However, the vaccine will not necessarily be located exclusively in the dermis. The dermis is the layer in the skin located between about 1.0 and about 2.0 mm from the surface in human skin, but there is a certain amount of variation between individuals and in different parts of the body. In general, it can be expected to reach the dermis by going 1.5 mm below the surface of the skin. The dermis is located between the stratum corneum and the epidermis at the surface and the subcutaneous layer below. Depending on the mode of delivery, the vaccine may ultimately be located solely or primarily within the dermis, or it may ultimately be distributed within the epidermis and the dermis.

[0317] A preferred embodiment of the invention is a method of preventing or treating staphylococcal infection or disease comprising the step of administering the immunogenic composition or vaccine of the invention to a patient in need thereof.

[0318] In a preferred embodiment, the patient is awaiting elective surgery.

[0319] A further preferred embodiment of the invention is a use of the immunogenic composition of the invention in the manufacture of a vaccine for treatment or prevention of staphylococcal infection or disease, preferably post-surgery staphylococcal infection.

[0320] The term `staphylococcal infection` encompasses infection caused by S. aureus and/or S. epidermidis and other staphylococcal strains capable of causing infection in a mammalian, preferably human host.

[0321] The terms "comprising", "comprise" and "comprises" herein are intended by the inventors to be optionally substitutable with the terms "consisting of", "consist of" and "consists of", respectively, in every instance.

[0322] All references or patent applications cited within this patent specification are incorporated by reference herein.

[0323] In order that this invention may be better understood, the following examples are set forth. These examples are for purposes of illustration only, and are not to be construed as limiting the scope of the invention in any manner.

EXAMPLES

Example 1 Construction of Plasmid to Express Recombinant Proteins

A: Cloning

[0324] Appropriate restriction sites engineered into oligonucleotides specific for the staphylococcal gene permitted directional cloning of the PCR product into the E. coli expression plasmid pET24d or pQE-30 such that a protein could be expressed as a fusion protein containing a (His)6 affinity chromatography tag at the N- or C-terminus.

[0325] The primers used were: TABLE-US-00008 Alpha toxin - 5'-CGCGGATCCGCAGATTCTGATATTAATATTAAAAC-3' and 5'CCCAAGCTTTTAATTTGTCATTTCTTCTTTTTC-3' EbpS - 5'-CGCGGATCCGCTGGGTCTAATAATTTTAAAGATG-3' and 5'CCCAAGCTTTTATGGAATAACGATTTGTTG-3' ClfA - 5'-CGCGGATCCAGTGAAAATAGTGTTACGCAATC-3' and 5'CCCAAGCTTTTACTCTGGAATTGGTTCAATTTC-3' FnbpA - 5'-CGCGGATCCACACAAACAACTGCAACTAACG-3' and 5'CCCAAGCTTTTATGCTTTGTGATTCTTTTTCAAAC3' Sbi - 5'-CGCGGATCCAACACGCAACAAACTTC-3 and 5'GGAACTGCAGTTATTTCCAGAATGATAATAAATTAC-3' SdrC - 5'-CGCGGATCCGCAGAACATACGAATGGAG-3' and 5'CCCAAGCTTTTATGTTTCTTCTTCGTAGTAGC-3' SdrG - 5'-CGCGGATCCGAGGAGAATTCAGTACAAG-3' and 5'CCCAAGCTTTTATTCGTCATCATAGTATCCG-3' Ebh - 5'-AAAAGTACTCACCACCACCACCACC-3' and 5'AAAAGTACTCACTTGATTCATCGCTTCAG-3' Aaa - 5'-GCGCGCCATGGCACAAGCTTCTACACAACATAC-3' and 5'GCGCGCTCGAGATGGATGAATGCATAGCTAGA-3' IsaA - 5'-GCATCCATGGCACCATCACCATCACCACGAAGTAAACGTTGATCAAG C-3' and 5'-AGCACTCGAGTTAGAATCCCCAAGCACCTAAACC-3' HarA - 5'-GCACCCATGGCAGAAAATACAAATACTTC-3' and 5'TTTTCTCGAGCATTTTAGATTGACTAAGTTG-3 Autolysin glucosaminidase - 5'-CAAGTCCCATGGCTGAGACGACACAAGATCAAC-3' and 5'-CAGTCTCGAGTTTTACAGCTGTTTTTGGTTG-3' Autolysin amidase - 5'-AGCTCATATGGCTTATACTGTTACTAAACC-3' and 5'GCGCCTCGAGTTTATATTGTGGGATGTCG-3' IsdA - 5'-CAAGTCCCATGGCAACAGAAGCTACGAACGCAAC-3' and 5'ACCAGTCTCGAGTAATTCTTTAGCTTTAGAGCTTG-3' IsdB - 5'-TATTCTCGAGGCTTTGAGTGTGTCCATCATTTG-3' and 5'GAAGCCATGGCAGCAGCTGAAGAAACAGGTGG-3' MRPII - 5'-GATTACACCATGGTTAAACCTCAAGCGAAA-3' and 5'AGGTGTCTCGAGTGCGATTGTAGCTTCATT-3'

[0326] The PCR products were first introduced into the pGEM-T cloning vector (Novagen) using Top10 bacterial cells, according to the manufacturer's instructions. This intermediate construct was made to facilitate further cloning into an expression vector. Transformants containing the DNA insert were selected by restriction enzyme analysis. Following digestion, a .about.20 .mu.l aliquot of the reaction was analyzed by agarose gel electrophoresis (0.8% agarose in a Tris-acetate-EDTA (TAE) buffer). DNA fragments were visualized by UV illumination after gel electrophoresis and ethidium bromide staining. A DNA molecular size standard (1 Kb ladder, Life Technologies) was electrophoresed in parallel with the test samples and was used to estimate the size of the DNA fragments. Plasmid purified from selected transformants for each cloning was then sequentially digested to completion with appropriate restriction enzymes as recommended by the manufacturer (Life Technologies). The digested DNA fragment was then purified using silica gel-based spin columns prior to ligation with the pET24d or pQE-30 plasmid. Cloning of Ebh (H2 fragment), AaA, IsdA, IsdB, HarA, Atl-amidase, Atl-glucosamine, MRP, IsaA was carried out using the pET24d plasmid and cloning of ClfA, SdrC, SdrE, FnbpA, SdrG/Fbe, alpha toxin and Sbi were carried out using the pQE-30 plasmid.

B: Production of Expression Vector

[0327] To prepare the expression plasmid pET24d or pQE-30 for ligation, it was similarly digested to completion with appropriate restriction enzymes. An approximately 5-fold molar excess of the digested fragments to the prepared vector was used to program the ligation reaction. A standard .about.20 .mu.l ligation reaction (.about.16.degree. C., .about.16 hours), using methods well known in the art, was performed using T4 DNA ligase (.about.2.0 units/reaction, Life Technologies). An aliquot of the ligation (.about.5 .mu.l) was used to transform M15(pREP4) or BT21::DE3 electro-competent cells according to methods well known in the art. Following a .about.2-3 hour outgrowth period at 37.degree. C. in .about.1.0 ml of LB broth, transformed cells were plated on LB agar plates containing ampicillin (100 .mu.g/ml) and/or kanamycin (30 .mu.g/ml). Antibiotics were included in the selection. Plates were incubated overnight at 37.degree. C. for .about.16 hours. Individual ApR/KanR colonies were picked with sterile toothpicks and used to "patch" inoculate fresh LB ApR/KanR plates as well as a .about.1.0 ml LB Ap/Kan broth culture. Both the patch plates and the broth culture were incubated overnight at 37.degree. C. in either a standard incubator (plates) or a shaking water bath. A whole cell-based PCR analysis was employed to verify that transformants contained the DNA insert. Here, the .about.1.0 ml overnight LB Ap/Kan broth culture was transferred to a 1.5 ml polypropylene tube and the cells collected by centrifugation in a Beckmann microcentrifuge (.about.3 min., room temperature, .about.12,000.times.g). The cell pellet was suspended in .about.200 .mu.l of sterile water and a .about.10 .mu.l aliquot used to program a .about.50 .mu.l final volume PCR reaction containing both forward and reverse amplification primers. The initial 95.degree. C. denaturation step was increased to 3 minutes to ensure thermal disruption of the bacterial cells and liberation of plasmid DNA. An ABI Model 9700 thermal cycler and a 32 cycle, three-step thermal amplification profile, i.e. 95.degree. C., 45 sec; 55-58.degree. C., 45 sec, 72.degree. C., 1 min., were used to amplify the BASB203 fragment from the lysed transformant samples. Following thermal amplification, a .about.20 .mu.l aliquot of the reaction was analyzed by agarose gel electrophoresis (0.8% agarose in a Tris-acetate-EDTA (TAE) buffer). DNA fragments were visualised by UV illumination after gel electrophoresis and ethidium bromide staining. A DNA molecular size standard (1 Kb ladder, Life Technologies) was electrophoresed in parallel with the test samples and was used to estimate the size of the PCR products. Transformants that produced the expected size PCR product were identified as strains containing a protein expression construct. Expression plasmid containing strains were then analyzed for the inducible expression of recombinant protein.

C: Expression Analysis of PCR-Positive Transformants

[0328] An aliquot of the overnight seed culture (.about.1.0 ml) was inoculated into a 125 ml erlenmeyer flask containing .about.25 ml of LB Ap/Kan broth and was grown at 37.degree. C. with shaking (.about.250 rpm) until the culture turbidity reached O.D.600 of .about.0.5, i.e. mid-log phase (usually about 1.5-2.0 hours). At this time approximately half of the culture (.about.12.5 ml) was transferred to a second 125 ml flask and expression of recombinant protein induced by the addition of IPTG (1.0 M stock prepared in sterile water, Sigma) to a final concentration of 1.0 mM. Incubation of both the IPTG-induced and non-induced cultures continued for an additional .about.4 hours at 37.degree. C. with shaking. Samples (.about.1.0 ml) of both induced and non-induced cultures were removed after the induction period and the cells collected by centrifugation in a microcentrifuge at room temperature for .about.3 minutes. Individual cell pellets were suspended in .about.50 .mu.l of sterile water, then mixed with an equal volume of 2.times. Laemelli SDS-PAGE sample buffer containing 2-mercaptoethanol, and placed in boiling water bath for .about.3 min to denature protein. Equal volumes (.about.15 .mu.l) of both the crude IPTG-induced and the non-induced cell lysates were loaded onto duplicate 12% Tris/glycine polyacrylamide gel (1 mm thick Mini-gels, Novex). The induced and non-induced lysate samples were electrophoresed together with prestained molecular weight markers (SeeBlue, Novex) under conventional conditions using a standard SDS/Tris/glycine running buffer (BioRad). Following electrophoresis, one gel was stained with commassie brilliant blue R250 (BioRad) and then destained to visualize novel IPTG-inducible protein(s). The second gel was electroblotted onto a PVDF membrane (0.45 micron pore size, Novex) for .about.2 hrs at 4.degree. C. using a BioRad Mini-Protean II blotting apparatus and Towbin's methanol (20%) transfer buffer. Blocking of the membrane and antibody incubations were performed according to methods well known in the art. A monoclonal anti-RGS (His)3 antibody, followed by a second rabbit anti-mouse antibody conjugated to HRP (QiaGen), were used to confirm the expression and identity of the recombinant protein. Visualization of the anti-His antibody reactive pattern was achieved using either an ABT insoluble substrate or using Hyperfilm with the Amersham ECL chemiluminescence system.

Example 2

Production of Recombinant Protein

Bacterial Strain

[0329] A recombinant expression strain of E. coli M15(pREP4) containing a plasmid (pQE30) or BL21::DE3 containing plasmid pET24d encoding staphylococcal protein was used to produce cell mass for purification of recombinant protein.

Media

[0330] The fermentation medium used for the production of recombinant protein consisted of 2.times.YT broth (Difco) containing 100 .mu.g/ml Ap and/or 30 .mu.g/ml Km. Antifoam was added to medium for the fermentor at 0.25 ml/L (Antifoam 204, Sigma). To induce expression of the recombinant protein, IPTG (Isopropyl .beta.-D-Thiogalactopyranoside) was added to the fermentor (1 mM, final).

Production of Recombinant Proteins

Under Native Conditions

[0331] IPTG was added at a final concentration of 1 mM and the culture was grown for 4 additional hours. The culture was then centrifuged at 6,000 rpm for 10 minutes and the pellet was resuspended in phosphate buffer (50 mM K2HPO4, KH2PO4 pH 7) including a protease inhibior cocktail. This sample was subjected to French pressure lysis using 1500 bar pressure (2 runs). After centrifugation for 30 minutes at 15,000 rpm, the supernatant was reserved for further purification and NaCl was added to 0.5M. The sample was then loaded on a Ni-NTA resin (XK 16 column Pharmacia, Ni-NTA resin Qiagen) conditioned in 50 mM K2HPO4, KH2PO4 pH 7. After loading the sample, the column was washed with Buffer A (0.2M NaH2PO4 pH7, 0.3M NaCl, 10% glycerol). To elute bound protein, a step gradient was used where different proportions of buffer B (0.2M NaH2PO4 pH7, 0.3M NaCl, 10% glycerol and 200 mM imidazole) were added to buffer A. The proportion of buffer B was gradually increased from 10% to 100%. After purification, eluted fraction containing the protein were pooled, concentrated and dialysed against 0.002M KH2PO4/K2HPO4 pH7, 0.15M NaCl.

[0332] This method was used to purify ClfA, SdrG, IsdA, IsaB, HarA, Atl-glucosamine and alpha toxin.

Under Denaturing Conditions

[0333] IPTG was added at a final concentration of 1 mM and the culture was grown for 4 additional hours. The culture was then centrifuged at 6,000 rpm for 10 minutes and the pellet was resuspended in phosphate buffer (50 mM K2HPO4, KH2PO4 pH 7) including a protease inhibior cocktail. This sample was subjected to French pressure lysis using 1500 bar pressure (2 runs). After centrifugation for 30 minutes at 15,000 rpm, the pellet was washed with phosphate buffer including 1M urea. The sample was centrifuged for 30 mins at 15000 rpm and the pellet was resuspended in 8M urea, 0.1M NaH2PO4, 0.5M NaCl, 0.01M Tris-HCl pH8 and kept overnight at room temperature. The sample was centrifuged for 20 minutes at 15000 rpm and the supernatant was collected for further purification. The sample was then loaded on a Ni-NTA resin (XK 16 column Pharmacia, Ni-NTA resin Qiagen) conditioned in 8M urea, 0.1M NaH2PO4, 0.5M NaCl, 0.01M Tris-HCl pH8. After passage of the flowthrough, the column was washed successively with buffer A (8M Urea, 0.1MNaH2PO4, 0.5M NaCl, 0.01M Tris, pH 8.0), buffer C (8M Urea, 0.1 MNaH2PO4, 0.5M NaCl, 0.01M Tris, pH 6.3), buffer D (8M Urea, 0.1MNaH2PO4, 0.5M NaCl, 0.01M Tris, pH 5.9) and buffer E (8M Urea, 0.1MNaH2PO4, 0.5M NaCl, 0.01M Tris, pH 4.5). The recombinant protein was eluted from the column during washes with buffer D and E. The denatured, recombinant protein could be solubilized in a solution devoid of urea. For this purpose, denatured protein contained in 8M urea was successively dialyzed against 4M urea, 0.1M Na2PO4, 0.01M Tris-HCl, pH7.1, 2M urea, 0.1 M NaH2PO4, 0.01M Tris-HCl, pH 7.1, 0.5M arginine and 0.002M KH2PO4/K2HPO4 pH7.1, 0.15M NaCl, 0.5M arginine.

[0334] This method was used to purify Ebh (H2 fragment), AaA, SdrC, FnbpA, Sbi, Atl-amidase and IsaA.

[0335] The purified proteins were analysed by SDS-PAGE. The results for one protein purified under native conditions (alpha toxin) and one protein purified under denaturing conditions (SdrC) are shown in FIGS. 3 and 4.

Example 3

Preparation of Polysaccharides

[0336] PIA (PNAG) is prepared as described in Joyce et al 2003, Carbohydrate Research 338; 903-922.

[0337] Type 5 and type 8 polysaccharides is extracted from S. aureus as described in Infection and Immunity 58 (7); 2367.

Activation and Coupling Chemistry:

[0338] Native polysaccharide is dissolved in NaCl 2M or in water. The optimal polysaccharide concentration is evaluated for all the serotypes and is between 2 mg/ml and 5 mg/ml.

[0339] From a 100 mg/ml stock solution in acetonitrile, CDAP (CDAP/PS ratio:0.75 mg/mg PS) is added to the polysaccharide solution. 1.5 minute later, 0.2M triethylamine is added to obtain the specific activation pH (pH 8.5-10.0). The activation of the polysaccharide is performed at this pH during 2 minutes at 25.degree. C. The carrier protein is added to the activated polysaccharide in an amount sufficient to give a 1/1 molar ratio and the coupling reaction is performed at the specific pH for 1 hour.

[0340] Then, the reaction is quenched with glycine for 30 minutes at 25.degree. C. and overnight at 4.degree. C.

[0341] The conjugates are purified by gel filtration using a Sephacryl 500HR gel filtration column equilibrated with 0.2M NaCl.

[0342] The carbohydrate and protein contents of the eluted fractions are determined. The conjugates are pooled and sterile filtered on a 0.22 .mu.m sterilizing membrane. The PS/Protein ratios in the conjugate preparations are determined.

Characterisation:

[0343] Each conjugate is characterised for protein and polysaccharide content. The polysaccharide content is measured by the Resorcinol test and the protein content by the Lowry test. The final PS/PD ratio (w/w) is determined by the ratio of the concentrations.

Residual DMAP Content (ng/.mu.g PS):

[0344] The activation of the polysaccharide with CDAP introduces a cyanate group in the polysaccharide and DMAP (4-dimethylamino-pyridin) is liberated. The residual DMAP content is determined by a specific assay developed and validated at GSK.

Free Polysaccharide Content (%):

[0345] The free polysaccharide content on conjugates kept at 4.degree. C. or stored 7 days at 37.degree. C. is determined on the supernatant obtained after incubation with .alpha.-carrier antibodies and saturated ammonium sulfate, followed by a centrifugation.

[0346] An .alpha.-PS/.alpha.-PS ELISA is used for the quantification of free polysaccharide in the supernatant. The absence of conjugate is also controlled by an .alpha.-carrier/.alpha.-PS ELISA.

Example 4

Formulation

Adjuvant Compositions

[0347] Protein, either individually or together, from the above examples may be formulated with the staphylococcal polysaccharide combination and as adjuvant, the formulation may comprise a mixture of 3 de --O-acylated monophosphoryl lipid A (3D-MPL) and aluminium hydroxide, or of 3 de --O-acylated monophosphoryl lipid A (3D-MPL) and aluminium phosphate, or 3D-MPL and/or QS21 optionally in an oil/water emulsion, and optionally formulated with cholesterol, or aluminium salt alone, preferably aluminium phosphate.

[0348] 3D-MPL: is a chemically detoxified form of the lipopolysaccharide (LPS) of the Gram-negative bacteria Salmonella minnesota.

[0349] Experiments performed at GSK Biologicals have shown that 3D-MPL combined with various vehicles strongly enhances both the humoral and a TH1 type of cellular immunity.

[0350] QS21: is one saponin purified from a crude extract of the bark of the Quillaja Saponaria Molina tree, which has a strong adjuvant activity: it activates both antigen-specific lymphoproliferation and CTLs to several antigens.

[0351] Vaccine containing an antigen of the invention containing 3D-MPL and alum may be prepared in analogous manner to that described in WO93/19780 or 92/16231. Experiments performed at GSK Biologicals have demonstrated a clear synergistic effect of combinations of 3D-MPL and QS21 in the induction of both humoral and TH1 type cellular immune responses. Vaccines containing an antigen such antigens are described in U.S. Pat. No. 5,750,110.

[0352] An oil/water emulsion may be composed of 2 oils (a tocopherol and squalene), and of PBS containing Tween 80 as emulsifier. The emulsion comprised 5% squalene 5% tocopherol 0.4% Tween 80 and had an average particle size of 180 nm and is known as SB62 (see WO 95/17210).

[0353] Experiments performed at GSK Biologicals have proven that the adjunction of this O/W emulsion to MPL/QS21 further increases their immunostimulant properties.

Preparation of Emulsion SB62 (2 Fold Concentrate)

[0354] Tween 80 is dissolved in phosphate buffered saline (PBS) to give a 2% solution in the PBS. To provide 100 ml two fold concentrate emulsion 5 g of DL alpha tocopherol and 5 ml of squalene are vortexed to mix thoroughly. 90 ml of PBS/Tween solution is added and mixed thoroughly. The resulting emulsion is then passed through a syringe and finally microfluidised by using an M110S microfluidics machine. The resulting oil droplets have a size of approximately 180 nm.

Example 5

Animal Experiments

[0355] Female CD-1 mice, 8 to 10 weeks old, are obtained from Charles River Laboratories, Kingston, Mass. For lethality studies, five groups of 9 to 11 CD-1 mice are challenged intraperitoneally (i.p.) with serial dilutions of S. aureus grown on CSA plates. The inocular sizes range from .about.10.sup.10 to 10.sup.8 CFU/mouse. Mortality is assessed on a daily basis for 3 days. The 50% lethal doses (LD.sub.50s) is estimated by using a probit model of the dose-response relationship. The null hypothesis of common LD.sub.50s was tested by the likelihood ratio test. Sublethal bacteremia is initiated by challenging groups of 8 to 20 mice by the intravenous (i.v.) route with .about.2.times.10.sup.6 CFU/mouse or by the i.p. route with .about.2.times.10.sup.7 CFU/mouse. After inoculation separate groups of animals are bled from the tail at specified times, and the bacteremia levels are estimated by quantitative plate counts performed in duplicate on tryptic soy agar plates with 5% sheep blood (Becton Dickinson Microbiology Systems). Statistical significance is determined with the Welch modification of the unpaired Stutent's t test.

Example 6

General Methodology of Determining Antibody Responses in Various Mammals

[0356] The sera were tested for IgG antibodies to the staphylococcal polysaccharides by an ELISA. Briefly, purified capsular polysaccharides from ATCC (Rockville, Md., 20852) are coated at 25 .mu.g/ml in phosphate buffered saline (PBS) on high binding microtitre plates (Nunc Maxisorp) overnight at 4 C. The plates are blocked with 10% fetal calf serum (FCS), 1 hour at 37 C. Serum samples are pre-incubated with the 20 .mu.g/ml cell-wall polysaccharide (Statens Serum Institute, Copenhagen) and 10% FCS at room temperature for 30 minutes to neutralize antibodies to this antigen. The samples are then diluted two-fold on the microplate in 10% FCS in PBS, and equilibrated at room temperature for 1 hour with agitation. After washing, the microplates are equilibrated with peroxidase labelled anti-human IgG Fc monoclonal antibody (HP6043-HRP, Stratech Scientific Ltd.) diluted 1:4000 in 10% FCS in PBS for 1 hour at room temperature with agitation. The ELISA is performed to measure rat IgG using Jackson ImmunoLaboratories Inc. peroxidase-conjugated AffiniPure Goat anti-Rat IgG (H+L) (code 112-035-003) at 1:5000. The titration curves are referenced to standard sera for each serotype using logistic log comparison by SoftMax Pro, The polysaccharide concentrations used to coat the ELISA plate are 10-20 .mu.g/ml. The color is developed using 4 mg OPD (Sigma) per 10 ml pH 4.5 0.1M citrate buffer with 14 .mu.l H2O2 for 15 minutes in the dark at room temperature. The reaction is stopped with 50 .mu.l HCl, and the optical density is read at 490 nm relative to 650 nm. IgG concentrations are determined by reference of titration points to the calibration curve modeled using a 4-parameter logistic log equation calculated by SoftMax Pro software.

[0357] The ELISA to measure the murine and rat IgG to the staphylococcal polysaccharides is similar with the following exceptions. Jackson ImmunoLaboratories Inc. peroxidase-conjugated affiniPure Goat Anti-mouse IgG (H+L) and AffiniPure Goat Anti-rat IgG (H+L) were employed to detect bound IgG.

[0358] HP6043-HRP reacts equally with human and Rhesus purified IgG, and so this reagent is used for Rhesus antiserum.

[0359] The protein ELISA is performed similarly to the polysaccharide ELISA with the following modifications. The protein is coated overnight at 2.0 .mu.g/ml in PBS. The serum samples are diluted in PBS containing 10% foetal calf serum and 0.1% polyvinyl alcohol. Bound human antibody is detected using Sigma Peroxidase-conjugated goat affinity purified antibody to Human IgG Fc (reference A-2290).

Example 7

Opsonophagocytosis Assay

[0360] The in vitro opsonophagocytosic killing of S. aureus by human polymorphonuclear leykocytes (PMNs) is performed as described in Xu et al 1992 Infect. Immun. 60; 1358. Human PMNs are prepared from heparinized blood by sedimentation in 3% dextran T-250. The opsonic reaction mixture (1 ml) contains .about.10.sup.6 PMNs in RPMI 1640 medium supplemented with 10% heat-inactivated fetal calf serum, .about.10.sup.8 CFU of S-aureus, and 0.1 ml of the test serum or IgG preparation. Hyperimmunized rabbit serum is used as a positive control, and 0.1 ml of nonimmune rabbit serum was used as a complete source for the IgG samples. The reaction mixtures are incubated at 37.degree. C., and bacterial samples are transferred at 0, 60, and 120 min into water and subsequently diluted, spread on tryptic soy agar plates, and incubated at 37.degree. C. for bacterial count after overnight incubation.

Example 8

Immunogenicity of Staphylococcal Proteins in Mice and Rabbits

[0361] Animals were immunized with purified staphylococcal proteins in order to generate hyper-immune sera. Mice were immunized three times (days 0, 14 and 28) with 10 .mu.g of each proteins adjuvanted in Specol. Rabbits were immunized three times (days 0, 21 and 42) with 20 .mu.g of each proteins adjuvanted in Specol. Immune sera were collected and evaluated in anti-protein and anti-killed whole cells ELISA.

Anti-Protein ELISA:

[0362] The purified protein was coated at 1 .mu.g/ml in phosphate buffered saline (PBS) on high binding microtitre plates (Nunc Maxisorp) overnight at 4.degree. C. The plates were blocked with PBS-BSA 1%, for 30 min at RT with agitation. The test samples were then diluted 1/1000 and incubated at room temperature for 1 hour with agitation. After washing, bound murine or rabbit antibody was detected using Jackson ImmunoLaboratories Inc. peroxidase-conjugated affiniPure Goat Anti-Mouse IgG (H+L) (ref: 115-035-003) or AffiniPure Goat Anti-Rabbit IgG (H+L) (ref: 11-035-003) diluted 1:5000 in PBS-tween 0.05%. The detection antibodies were incubated for 30 min. at room temperature with agitation. The color was developed using 4 mg OPD (Sigma)+5 .mu.l H2O2 per 10 ml pH 4.5 0.1M citrate buffer for 15 minutes in the dark at room temperature. The reaction was stopped with 50 .mu.l HCl, and the optical density was read at 490 nm relative to 650 nm.

[0363] The O.D. for a 1/1000 dilution of Post III was compared to the O.D. obtained with the same dilution of Pre-immune sera.

[0364] Results generated with mice and rabbit sera are presented in FIG. 5. A good seroconversion against each antigen was observed. Evaluation of sera directed against SBI was impaired due to the Ig binding activity of this protein.

Anti-Killed Whole Cells ELISA:

[0365] Killed whole cells (heat or formaldehyde inactivated) from S. aureus type 5 and 8 or S. epidermidis strain Hay were coated at 20 .mu.g/ml in phosphate buffered saline (PBS) on high binding microtitre plates (Nunc Maxisorp) overnight at 40 C with evaporation. The plates were blocked with PBS-BSA 1% 30 min at room temperature with agitation. Protein A was neutralised by addition of 10 .mu.g/ml of Affinity Purified Chickedn anti-ProteinA (ICL ref: CPA-65A-2) diluted in PBS-tween 0.05% followed by incubation for 1 hour at room temperature. The test samples were then diluted two-fold on the microplate in PBS-0.05% from a starting dilution at 1/10 and incubated 1 hour at room temperature with agitation. After washing, bound murine or rabbit antibody was detected using Jackson ImmunoLaboratories Inc. peroxidase-conjugated affiniPure Goat Anti-Mouse IgG (H+L) (ref: 115-035-003) or AffiniPure Goat Anti-Rabbit IgG (H+L) (ref: 11-035-003) diluted 1:5000 in PBS-tween 0.05%. This detection antibodies were incubated for 30 min. at room temperature with agitation. The color was developed using 4 mg OPD (Sigma)+5 .mu.l H2O2 per 10 ml pH 4.5 0.1M citrate buffer for 15 minutes in the dark, at room temperature. The reaction was stopped with 50 .mu.l HCl, and the optical density was read at 490 nm relative to 650 nm.

[0366] It should be noted that expression levels of proteins in staphylococci will vary depending on culture conditions. Therefore a negative result may reflect the choice of incorrect culture conditions rather than a lack of immunogenicity.

[0367] The results using mice sera are shown in Table 5 and some of the graphs are shown in FIG. 6. A weak recognition of S. aureus strain 5 is observed with sera directed against SdrC, FnbpA, Ebh, Sbi and IsaA. Recognition of S. aureus strain 8 is only observed with the serum directed against Sbi. Weak recognition of S. epidermidis Hay is observed with sera directed against Atl amidase, MRP, IsdA, IsaA, Ebh, Aaa and Sbi.

[0368] A selection of results generated using rabbit sera are shown in FIG. 7 and summarized in Table 6. Very good recognition of the three strains was observed with IsaA and IsdB. A weak recognition of the three stains was observed with HarA although animals only received one injection rather than the three injections used for the other proteins. TABLE-US-00009 TABLE 5 Protein name React on SA5 React on SA8 React on SE Hay IsaA (+) (+) (+) ClfA - (+) (+) Atl amidase - - ++ SdrG - - - Glucosamidase - - - IsdA - - ++ Alpha toxin - - - SrdC ++ (+) - Ebh + - + AaA - - ++ MRP - - ++ Sbi ++ ++ +++ FnbpA + + (+)

[0369] TABLE-US-00010 TABLE 6 Protein name React on SA5 React on SA8 React on SE Hay IsaA +++ +++ +++ ClfA + ++ ++ Atl amidase - ++ + IsdB +++ +++ +++ SdrG + + + Glucosamidase - - - HarA (1 inject.) + + + IsdA - - - Alpha toxin - - + SrdC - - - Ebh - + - AaA - - - MRP - - ++ Sbi - +++ - FnbpA - ++ ++

Example 8

Efficacy of Combinations of Staphylococcal Proteins in a Nasal Colonization Model

[0370] Fifteen groups of three cotton rats were inoculated with combinations of eight staphylococcal antigens and five cotton rats which acted as controls were treated with no antigen. These sixteen groups are as follows:

Group 1--Atl-glucosamine, Atl-amidase, AAA, alpha toxin, SdrC, SdrG, Ebh, Sbi

Group 2--Atl-glucosamine, Atl-amidase, IsdA, IsdB, ClfA, SdrC, Ebh, FnbpA

Group 3--Atl-glucosamine, Atl-amidase, HarA, IsdA, MRP, IsdB, AAA, alpha toxin

Group 4--Atl-glucosamine, HarA, IsdA, AAA, ClfA, IsaA, Ebh, Sbi

Group 5--HarA, MRP, AAA, alpha toxin, ClfA, SdrC, Ebh, FnbpA

Group 6--IsdA, IsdB, AAA, alpha toxin, ClfA, SdrG, Sbi, FnbpA

Group 7--Atl-aminidase, IsdA, MRP, AAA, IsaA, SdrG, Ebh, FnbpA

Group 8--Control

Group 9--Atl-glucosamine, IsdA, MRP, alpha toxin, IsaA, SdrC, Sbi, FnbpA

Group 10--Atl-glucosamine, MRP, IsdB, AAA, ClfA, IsaA, SdrC, SdrG

Group 11--Atl-amindase, MRP, IsdB, alpha toxin, ClfA, IsaA, Ebh, Sbi

Group 12--Atl-glucosamine, HarA, IsdB, alpha toxin, IsaA, SdrG, Ebh, FnbpA

Group 13--Atl-amidase, HarA, IsdB, AAA, IsaA, SdrC, Sbi, FnbpA

Group 14--Atl-glucosamine, Atl-amidase, HarA, MRP, ClfA, SdrG, Sbi, FnbpA

Group 15--Atl-amidase, HarA, IsdA, alpha toxin, ClfA, IsaA, SdfC, SdrG

Group 16--HarA, IsdA, MRP, IsdB, SdrC, SdrG, Ebh, Sbi

[0371] Each mix of antigens contained 3 .mu.g of each antigen mixed with an adjuvant made of liposomes containing MPL and QS21. The cotton rats were inoculated three times on days 1, 14 and 28 of the experiment. Two weeks after inoculation, the efficacy of the immunisations were assessed using a nasal colonisation assay as described in Kokai-Kun et al (2003) Antimicrob. Agents. Chemother. 47; 1589-1597.

[0372] Classical multiple linear regression analysis was carried out on the data using "Design Expert 6" software. The presence of an antigen was coded as +1 and the absence of an antigen by -1. Using the equation of the model it was possible to determine which antigens were the key antigens which produced a large decrease in the number of colonies per nose.

Results

[0373] The results of the nasal colonisation assay are shown in Table 7. The control group had a mean logCFU/nose of 3.51335 and a decrease in nasal colonisation could be see for all the groups of cotton rats inoculated with staphylococcal proteins. Groups 4, 9 and 13 showed the greatest decrease in nasal colonisation with a decrease of over 2 logs in CFU/nose. Groups 12 and 16 also gave good results, showing a decease of about 2 logs in CFU/nose. TABLE-US-00011 TABLE 7 Group Mean observed LogCFU/nose Predicted LogCFU/nose 1 1.77527 2.03560 2 2.90435 2.52684 3 1.96556 2.23033 4 1.27748 1.21872 5 1.67304 1.93128 6 2.79745 2.98193 7 2.21481 2.30705 8 3.51355 3.47317 9 1.22480 1.44080 10 2.03085 1.93204 11 2.02522 1.81581 12 1.53402 1.70996 13 1.36063 1.49100 14 2.31201 1.73909 15 2.22979 1.98223 16 1.58109 1.44004

[0374] The contribution of specific antigens within the antigen mix was calculated using multiple regression analysis of the nasal colonisation data. The final model contains the seven best antigens. Results for these antigens are shown in Table 8. Within the context of the protein mix, the inclusion of HarA gave the greatest decrease in nasal colonisation, followed by IsaA, Sbi, SdrC, autolysin-glucosamine, MRP and Ebh. TABLE-US-00012 TABLE 8 Effects in difference of logCFU/nose and ratio of CFU/nose for the seven best antigens in the model and corresponding p-values. Effect Reduction Cumulative Cumulative antigen prob > F estimate ratio effect ratio HarA 0.033 -0.596 3.9 -0.596 3.9 IsaA 0.046 -0.558 3.6 -1.154 14.3 Sbi 0.077 -0.491 3.1 -1.645 44.2 SdrC 0.22 -0.337 2.2 -1.982 96.0 Atl-glucos 0.238 -0.324 2.1 -2.306 202.2 MRP 0.239 -0.323 2.1 -2.629 425.3 Ebh 0.297 -0.286 1.9 -2.914 821.0

[0375]

Sequence CWU 1

1

74 1 533 PRT S. aureus 1 Met Leu Gln Val Thr Asp Val Ser Leu Arg Phe Gly Asp Arg Lys Leu 1 5 10 15 Phe Glu Asp Val Asn Ile Lys Phe Thr Glu Gly Asn Cys Tyr Gly Leu 20 25 30 Ile Gly Ala Asn Gly Ala Gly Lys Ser Thr Phe Leu Lys Ile Leu Ser 35 40 45 Gly Glu Leu Asp Ser Gln Thr Gly His Val Ser Leu Gly Lys Asn Glu 50 55 60 Arg Leu Ala Val Leu Lys Gln Asp His Tyr Ala Tyr Glu Asp Glu Arg 65 70 75 80 Val Leu Asp Val Val Ile Lys Gly His Glu Arg Leu Tyr Glu Val Met 85 90 95 Lys Glu Lys Asp Glu Ile Tyr Met Lys Pro Asp Phe Ser Asp Glu Asp 100 105 110 Gly Ile Arg Ala Ala Glu Leu Glu Gly Glu Phe Ala Glu Met Asn Gly 115 120 125 Trp Asn Ala Glu Ala Asp Ala Ala Asn Leu Leu Ser Gly Leu Gly Ile 130 135 140 Asp Pro Thr Leu His Asp Lys Lys Met Ala Glu Leu Glu Asn Asn Gln 145 150 155 160 Lys Ile Lys Val Leu Leu Ala Gln Ser Leu Phe Gly Glu Pro Asp Val 165 170 175 Leu Leu Leu Asp Glu Pro Thr Asn Gly Leu Asp Ile Pro Ala Ile Ser 180 185 190 Trp Leu Glu Asp Phe Leu Ile Asn Phe Asp Asn Thr Val Ile Val Val 195 200 205 Ser His Asp Arg His Phe Leu Asn Asn Val Cys Thr His Ile Ala Asp 210 215 220 Leu Asp Phe Gly Lys Ile Lys Val Tyr Val Gly Asn Tyr Asp Phe Trp 225 230 235 240 Tyr Gln Ser Ser Gln Leu Ala Gln Lys Met Ala Gln Glu Gln Asn Lys 245 250 255 Lys Lys Glu Glu Lys Met Lys Glu Leu Gln Asp Phe Ile Ala Arg Phe 260 265 270 Ser Ala Asn Ala Ser Lys Ser Lys Gln Ala Thr Ser Arg Lys Lys Gln 275 280 285 Leu Glu Lys Ile Glu Leu Asp Asp Ile Gln Pro Ser Ser Arg Arg Tyr 290 295 300 Pro Phe Val Lys Phe Thr Pro Glu Arg Glu Ile Gly Asn Asp Leu Leu 305 310 315 320 Ile Val Gln Asn Leu Ser Lys Thr Ile Asp Gly Glu Lys Val Leu Asp 325 330 335 Asn Val Ser Phe Thr Met Asn Pro Asn Asp Lys Ala Ile Leu Ile Gly 340 345 350 Asp Ser Glu Ile Ala Lys Thr Thr Leu Leu Lys Ile Leu Ala Gly Glu 355 360 365 Met Glu Pro Asp Glu Gly Ser Phe Lys Trp Gly Val Thr Thr Ser Leu 370 375 380 Ser Tyr Phe Pro Lys Asp Asn Ser Glu Phe Phe Glu Gly Val Asn Met 385 390 395 400 Asn Leu Val Asp Trp Leu Arg Gln Tyr Ala Pro Glu Asp Glu Gln Thr 405 410 415 Glu Thr Phe Leu Arg Gly Phe Leu Gly Arg Met Leu Phe Ser Gly Glu 420 425 430 Glu Val Lys Lys Lys Ala Ser Val Leu Ser Gly Gly Glu Lys Val Arg 435 440 445 Cys Met Leu Ser Lys Met Met Leu Ser Ser Ala Asn Val Leu Leu Leu 450 455 460 Asp Glu Pro Thr Asn His Leu Asp Leu Glu Ser Ile Thr Ala Val Asn 465 470 475 480 Asp Gly Leu Lys Ser Phe Lys Gly Ser Ile Ile Phe Thr Ser Tyr Asp 485 490 495 Phe Glu Phe Ile Asn Thr Ile Ala Asn Arg Val Ile Asp Leu Asn Lys 500 505 510 Gln Gly Gly Val Ser Lys Glu Ile Pro Tyr Glu Glu Tyr Leu Gln Glu 515 520 525 Ile Gly Val Leu Lys 530 2 535 PRT S. epidermidis 2 Met Leu Gln Val Thr Asp Val Ser Leu Arg Phe Gly Asp Arg Lys Leu 1 5 10 15 Phe Glu Asp Val Asn Ile Lys Phe Thr Glu Gly Asn Cys Tyr Gly Leu 20 25 30 Ile Gly Ala Asn Gly Ala Gly Lys Ser Thr Phe Leu Lys Ile Leu Ser 35 40 45 Gly Glu Ile Asp Ser Gln Thr Gly His Val Ser Leu Gly Lys Asp Glu 50 55 60 Arg Leu Ala Val Leu Lys Gln Asp His Phe Ala Tyr Glu Asp Glu Arg 65 70 75 80 Val Leu Asp Val Val Ile Lys Gly His Glu Arg Leu Tyr Gln Val Met 85 90 95 Lys Glu Lys Asp Glu Ile Tyr Met Lys Pro Asp Phe Ser Asp Glu Asp 100 105 110 Gly Ile Arg Ala Ala Glu Leu Glu Gly Glu Phe Ala Glu Met Asn Gly 115 120 125 Trp Asn Ala Glu Ala Asp Ala Ala Asn Leu Leu Ser Gly Leu Gly Ile 130 135 140 Glu Pro Asp Leu His Asp Lys Asn Met Ser Glu Leu Glu Asn Asn Gln 145 150 155 160 Lys Val Lys Val Leu Leu Ala Gln Ser Leu Phe Gly Asp Pro Asp Val 165 170 175 Leu Leu Leu Asp Glu Pro Thr Asn Gly Leu Asp Ile Pro Ala Ile Ser 180 185 190 Trp Leu Glu Asp Phe Leu Ile Asn Phe Glu Asn Thr Val Ile Val Val 195 200 205 Ser His Asp Arg His Phe Leu Asn Asn Val Cys Thr His Ile Ala Asp 210 215 220 Leu Asp Phe Gly Lys Ile Lys Leu Tyr Val Gly Asn Tyr Asp Phe Trp 225 230 235 240 Tyr Gln Ser Ser Gln Leu Ala Gln Lys Met Ala Gln Glu Gln Asn Lys 245 250 255 Lys Lys Glu Glu Lys Met Lys Glu Leu Gln Asp Phe Ile Ala Arg Phe 260 265 270 Ser Ala Asn Ala Ser Lys Ser Lys Gln Ala Thr Ser Arg Lys Lys Gln 275 280 285 Leu Glu Lys Ile Glu Leu Asp Asp Ile Gln Pro Ser Ser Arg Arg Tyr 290 295 300 Pro Tyr Val Lys Phe Thr Pro Glu Arg Glu Ile Gly Asn Asp Leu Leu 305 310 315 320 Thr Val Glu Asn Leu Ser Lys Thr Ile Asp Gly Glu Lys Val Leu Asp 325 330 335 Asn Val Ser Phe Thr Met Asn Pro Asn Asp Lys Ala Ile Leu Val Gly 340 345 350 Asp Ser Glu Ile Ala Lys Thr Thr Leu Leu Lys Ile Leu Ala Gly Glu 355 360 365 Met Glu Pro Asp Glu Gly Thr Phe Lys Trp Gly Val Thr Thr Ser Leu 370 375 380 Ser Tyr Phe Pro Lys Asp Asn Ser Glu Phe Phe Asp Gly Val Asp Met 385 390 395 400 Asn Leu Val Glu Trp Leu Arg Gln Tyr Ala Pro Glu Asp Glu Gln Thr 405 410 415 Glu Thr Phe Leu Arg Gly Phe Leu Gly Arg Met Leu Phe Ser Gly Glu 420 425 430 Glu Val Lys Lys Lys Ala Ser Val Leu Ser Gly Gly Glu Lys Val Arg 435 440 445 Cys Met Leu Ser Lys Met Met Leu Ser Ser Ala Asn Val Leu Leu Leu 450 455 460 Asp Glu Pro Thr Asn His Leu Asp Leu Glu Ser Ile Thr Ala Val Asn 465 470 475 480 Asp Gly Leu Lys Ser Phe Lys Gly Ser Ile Ile Phe Thr Ser Tyr Asp 485 490 495 Phe Glu Phe Ile Asn Thr Ile Ala Asn Arg Val Ile Asp Leu Asn Gln 500 505 510 Ala Gly Ala Leu Ser Lys Glu Val Pro Tyr Glu Glu Tyr Leu Gln Glu 515 520 525 Ile Gly Val Leu Gln Asn Asn 530 535 3 434 PRT S. aureus 3 Met Pro Ile Ile Thr Asp Val Tyr Ala Arg Glu Val Leu Asp Ser Arg 1 5 10 15 Gly Asn Pro Thr Val Glu Val Glu Val Leu Thr Glu Ser Gly Ala Phe 20 25 30 Gly Arg Ala Leu Val Pro Ser Gly Ala Ser Thr Gly Glu His Glu Ala 35 40 45 Val Glu Leu Arg Asp Gly Asp Lys Ser Arg Tyr Leu Gly Lys Gly Val 50 55 60 Thr Lys Ala Val Glu Asn Val Asn Glu Ile Ile Ala Pro Glu Ile Ile 65 70 75 80 Glu Gly Glu Phe Ser Val Leu Asp Gln Val Ser Ile Asp Lys Met Met 85 90 95 Ile Ala Leu Asp Gly Thr Pro Asn Lys Gly Lys Leu Gly Ala Asn Ala 100 105 110 Ile Leu Gly Val Ser Ile Ala Val Ala Arg Ala Ala Ala Asp Leu Leu 115 120 125 Gly Gln Pro Leu Tyr Lys Tyr Leu Gly Gly Phe Asn Gly Lys Gln Leu 130 135 140 Pro Val Pro Met Met Asn Ile Val Asn Gly Gly Ser His Ser Asp Ala 145 150 155 160 Pro Ile Ala Phe Gln Glu Phe Met Ile Leu Pro Val Gly Ala Thr Thr 165 170 175 Phe Lys Glu Ser Leu Arg Trp Gly Thr Glu Ile Phe His Asn Leu Lys 180 185 190 Ser Ile Leu Ser Lys Arg Gly Leu Glu Thr Ala Val Gly Asp Glu Gly 195 200 205 Gly Phe Ala Pro Lys Phe Glu Gly Thr Glu Asp Ala Val Glu Thr Ile 210 215 220 Ile Gln Ala Ile Glu Ala Ala Gly Tyr Lys Pro Gly Glu Glu Val Phe 225 230 235 240 Leu Gly Phe Asp Cys Ala Ser Ser Glu Phe Tyr Glu Asn Gly Val Tyr 245 250 255 Asp Tyr Ser Lys Phe Glu Gly Glu His Gly Ala Lys Arg Thr Ala Ala 260 265 270 Glu Gln Val Asp Tyr Leu Glu Gln Leu Val Asp Lys Tyr Pro Ile Ile 275 280 285 Thr Ile Glu Asp Gly Met Asp Glu Asn Asp Trp Asp Gly Trp Lys Gln 290 295 300 Leu Thr Glu Arg Ile Gly Asp Arg Val Gln Leu Val Gly Asp Asp Leu 305 310 315 320 Phe Val Thr Asn Thr Glu Ile Leu Ala Lys Gly Ile Glu Asn Gly Ile 325 330 335 Gly Asn Ser Ile Leu Ile Lys Val Asn Gln Ile Gly Thr Leu Thr Glu 340 345 350 Thr Phe Asp Ala Ile Glu Met Ala Gln Lys Ala Gly Tyr Thr Ala Val 355 360 365 Val Ser His Arg Ser Gly Glu Thr Glu Asp Thr Thr Ile Ala Asp Ile 370 375 380 Ala Val Ala Thr Asn Ala Gly Gln Ile Lys Thr Gly Ser Leu Ser Arg 385 390 395 400 Thr Asp Arg Ile Ala Lys Tyr Asn Gln Leu Leu Arg Ile Glu Asp Glu 405 410 415 Leu Phe Glu Thr Ala Lys Tyr Asp Gly Ile Lys Ser Phe Tyr Asn Leu 420 425 430 Asp Lys 4 434 PRT S. epidermidis 4 Met Pro Ile Ile Thr Asp Val Tyr Ala Arg Glu Val Leu Asp Ser Arg 1 5 10 15 Gly Asn Pro Thr Val Glu Val Glu Val Leu Thr Glu Ser Gly Ala Phe 20 25 30 Gly Arg Ala Leu Val Pro Ser Gly Ala Ser Thr Gly Glu His Glu Ala 35 40 45 Val Glu Leu Arg Asp Gly Asp Lys Ser Arg Tyr Leu Gly Lys Gly Val 50 55 60 Thr Lys Ala Val Glu Asn Val Asn Glu Met Ile Ala Pro Glu Ile Val 65 70 75 80 Glu Gly Glu Phe Ser Val Leu Asp Gln Val Ser Ile Asp Lys Met Met 85 90 95 Ile Gln Leu Asp Gly Thr His Asn Lys Gly Lys Leu Gly Ala Asn Ala 100 105 110 Ile Leu Gly Val Ser Ile Ala Val Ala Arg Ala Ala Ala Asp Leu Leu 115 120 125 Gly Gln Pro Leu Tyr Lys Tyr Leu Gly Gly Phe Asn Gly Lys Gln Leu 130 135 140 Pro Val Pro Met Met Asn Ile Val Asn Gly Gly Ser His Ser Asp Ala 145 150 155 160 Pro Ile Ala Phe Gln Glu Phe Met Ile Leu Pro Val Gly Ala Glu Ser 165 170 175 Phe Lys Glu Ser Leu Arg Trp Gly Ala Glu Ile Phe His Asn Leu Lys 180 185 190 Ser Ile Leu Ser Glu Arg Gly Leu Glu Thr Ala Val Gly Asp Glu Gly 195 200 205 Gly Phe Ala Pro Arg Phe Glu Gly Thr Glu Asp Ala Val Glu Thr Ile 210 215 220 Ile Lys Ala Ile Glu Lys Ala Gly Tyr Lys Pro Gly Glu Asp Val Phe 225 230 235 240 Leu Gly Phe Asp Cys Ala Ser Ser Glu Phe Tyr Glu Asn Gly Val Tyr 245 250 255 Asp Tyr Thr Lys Phe Glu Gly Glu His Gly Ala Lys Arg Ser Ala Ala 260 265 270 Glu Gln Val Asp Tyr Leu Glu Glu Leu Ile Gly Lys Tyr Pro Ile Ile 275 280 285 Thr Ile Glu Asp Gly Met Asp Glu Asn Asp Trp Glu Gly Trp Lys Gln 290 295 300 Leu Thr Asp Arg Ile Gly Asp Lys Val Gln Leu Val Gly Asp Asp Leu 305 310 315 320 Phe Val Thr Asn Thr Glu Ile Leu Ser Lys Gly Ile Glu Gln Gly Ile 325 330 335 Gly Asn Ser Ile Leu Ile Lys Val Asn Gln Ile Gly Thr Leu Thr Glu 340 345 350 Thr Phe Asp Ala Ile Glu Met Ala Gln Lys Ala Gly Tyr Thr Ala Val 355 360 365 Val Ser His Arg Ser Gly Glu Thr Glu Asp Thr Thr Ile Ala Asp Ile 370 375 380 Ala Val Ala Thr Asn Ala Gly Gln Ile Lys Thr Gly Ser Leu Ser Arg 385 390 395 400 Thr Asp Arg Ile Ala Lys Tyr Asn Gln Leu Leu Arg Ile Glu Asp Glu 405 410 415 Leu Tyr Glu Thr Ala Lys Phe Glu Gly Ile Lys Ser Phe Tyr Asn Leu 420 425 430 Asp Lys 5 255 PRT S. aureus 5 Met Lys Lys Ile Val Thr Ala Thr Ile Ala Thr Ala Gly Leu Ala Thr 1 5 10 15 Ile Ala Phe Ala Gly His Asp Ala Gln Ala Ala Glu Gln Asn Asn Asn 20 25 30 Gly Tyr Asn Ser Asn Asp Ala Gln Ser Tyr Ser Tyr Thr Tyr Thr Ile 35 40 45 Asp Ala Gln Gly Asn Tyr His Tyr Thr Trp Thr Gly Asn Trp Asn Pro 50 55 60 Ser Gln Leu Thr Gln Asn Asn Thr Tyr Tyr Tyr Asn Asn Tyr Asn Thr 65 70 75 80 Tyr Ser Tyr Asn Asn Ala Ser Tyr Asn Asn Tyr Tyr Asn His Ser Tyr 85 90 95 Gln Tyr Asn Asn Tyr Thr Asn Asn Ser Gln Thr Ala Thr Asn Asn Tyr 100 105 110 Tyr Thr Gly Gly Ser Gly Ala Ser Tyr Ser Thr Thr Ser Asn Asn Val 115 120 125 His Val Thr Thr Thr Ala Ala Pro Ser Ser Asn Gly Arg Ser Ile Ser 130 135 140 Asn Gly Tyr Ala Ser Gly Ser Asn Leu Tyr Thr Ser Gly Gln Cys Thr 145 150 155 160 Tyr Tyr Val Phe Asp Arg Val Gly Gly Lys Ile Gly Ser Thr Trp Gly 165 170 175 Asn Ala Ser Asn Trp Ala Asn Ala Ala Ala Ser Ser Gly Tyr Thr Val 180 185 190 Asn Asn Thr Pro Lys Val Gly Ala Ile Met Gln Thr Thr Gln Gly Tyr 195 200 205 Tyr Gly His Val Ala Tyr Val Glu Gly Val Asn Ser Asn Gly Ser Val 210 215 220 Arg Val Ser Glu Met Asn Tyr Gly His Gly Ala Gly Val Val Thr Ser 225 230 235 240 Arg Thr Ile Ser Ala Asn Gln Ala Gly Ser Tyr Asn Phe Ile His 245 250 255 6 267 PRT S. aureus 6 Met Lys Lys Ile Ala Thr Ala Thr Ile Ala Thr Ala Gly Phe Ala Thr 1 5 10 15 Ile Ala Ile Ala Ser Gly Asn Gln Ala His Ala Ser Glu Gln Asp Asn 20 25 30 Tyr Gly Tyr Asn Pro Asn Asp Pro Thr Ser Tyr Ser Tyr Thr Tyr Thr 35 40 45 Ile Asp Ala Gln Gly Asn Tyr His Tyr Thr Trp Lys Gly Asn Trp His 50 55 60 Pro Ser Gln Leu Asn Gln Asp Asn Gly Tyr Tyr Ser Tyr Tyr Tyr Tyr 65 70 75 80 Asn Gly Tyr Asn Asn Tyr Asn Asn Tyr Asn Asn Gly Tyr Ser Tyr Asn 85 90 95 Asn Tyr Ser Arg Tyr Asn Asn Tyr Ser Asn Asn Asn Gln Ser Tyr Asn 100 105 110 Tyr Asn Asn Tyr Asn Ser Tyr Asn Thr Asn Ser Tyr Arg Thr Gly Gly 115 120 125 Leu Gly Ala Ser Tyr Ser Thr Ser Ser Asn Asn Val Gln Val Thr Thr 130 135 140 Thr Met Ala Pro Ser Ser Asn Gly Arg Ser Ile Ser Ser Gly Tyr Thr 145 150 155 160 Ser Gly Arg Asn Leu Tyr Thr Ser Gly Gln Cys Thr Tyr Tyr Val Phe 165 170 175 Asp Arg Val Gly Gly Lys Ile Gly Ser Thr Trp Gly Asn Ala Ser Asn 180 185 190 Trp Ala Asn Ala Ala Ala Arg Ala Gly Tyr Thr Val Asn Asn Thr Pro 195 200 205 Lys Ala Gly Ala Ile Met Gln Thr Thr Gln Gly Ala Tyr Gly His Val 210 215 220 Ala Tyr Val Glu Ser Val Asn Ser Asn Gly Ser Val Arg Val Ser Glu 225 230 235

240 Met Asn Tyr Gly Tyr Gly Pro Gly Val Val Thr Ser Arg Thr Ile Ser 245 250 255 Ala Ser Gln Ala Ala Gly Tyr Asn Phe Ile His 260 265 7 257 PRT S. epidermidis 7 Met Lys Lys Ile Ala Thr Ala Thr Ile Ala Thr Ala Gly Ile Ala Thr 1 5 10 15 Phe Ala Phe Ala His His Asp Ala Gln Ala Ala Glu Gln Asn Asn Asp 20 25 30 Gly Tyr Asn Pro Asn Asp Pro Tyr Ser Tyr Ser Tyr Thr Tyr Thr Ile 35 40 45 Asp Ala Glu Gly Asn Tyr His Tyr Thr Trp Lys Gly Asn Trp Ser Pro 50 55 60 Asp Arg Val Asn Thr Ser Tyr Asn Tyr Asn Asn Tyr Asn Asn Tyr Asn 65 70 75 80 Tyr Tyr Gly Tyr Asn Asn Tyr Ser Asn Tyr Asn Asn Tyr Ser Asn Tyr 85 90 95 Asn Asn Tyr Asn Asn Tyr Gln Ser Asn Asn Thr Gln Ser Gln Arg Thr 100 105 110 Thr Gln Pro Thr Gly Gly Leu Gly Ala Ser Tyr Ser Thr Ser Ser Ser 115 120 125 Asn Val His Val Thr Thr Thr Ser Ala Pro Ser Ser Asn Gly Val Ser 130 135 140 Leu Ser Asn Ala Arg Ser Ala Ser Gly Asn Leu Tyr Thr Ser Gly Gln 145 150 155 160 Cys Thr Tyr Tyr Val Phe Asp Arg Val Gly Gly Lys Ile Gly Ser Thr 165 170 175 Trp Gly Asn Ala Asn Asn Trp Ala Asn Ala Ala Ala Arg Ser Gly Tyr 180 185 190 Thr Val Asn Asn Ser Pro Ala Lys Gly Ala Ile Leu Gln Thr Ser Gln 195 200 205 Gly Ala Tyr Gly His Val Ala Tyr Val Glu Gly Val Asn Ser Asn Gly 210 215 220 Ser Ile Arg Val Ser Glu Met Asn Tyr Gly His Gly Ala Gly Val Val 225 230 235 240 Thr Ser Arg Thr Ile Ser Ala Ser Gln Ala Ala Ser Tyr Asn Tyr Ile 245 250 255 His 8 309 PRT S. aureus 8 Met Lys Lys Leu Val Pro Leu Leu Leu Ala Leu Leu Leu Leu Val Ala 1 5 10 15 Ala Cys Gly Thr Gly Gly Lys Gln Ser Ser Asp Lys Ser Asn Gly Lys 20 25 30 Leu Lys Val Val Thr Thr Asn Ser Ile Leu Tyr Asp Met Ala Lys Asn 35 40 45 Val Gly Gly Asp Asn Val Asp Ile His Ser Ile Val Pro Val Gly Gln 50 55 60 Asp Pro His Glu Tyr Glu Val Lys Pro Lys Asp Ile Lys Lys Leu Thr 65 70 75 80 Asp Ala Asp Val Ile Leu Tyr Asn Gly Leu Asn Leu Glu Thr Gly Asn 85 90 95 Gly Trp Phe Glu Lys Ala Leu Glu Gln Ala Gly Lys Ser Leu Lys Asp 100 105 110 Lys Lys Val Ile Ala Val Ser Lys Asp Val Lys Pro Ile Tyr Leu Asn 115 120 125 Gly Glu Glu Gly Asn Lys Asp Lys Gln Asp Pro His Ala Trp Leu Ser 130 135 140 Leu Asp Asn Gly Ile Lys Tyr Val Lys Thr Ile Gln Gln Thr Phe Ile 145 150 155 160 Asp Asn Asp Lys Lys His Lys Ala Asp Tyr Glu Lys Gln Gly Asn Lys 165 170 175 Tyr Ile Ala Gln Leu Glu Lys Leu Asn Asn Asp Ser Lys Asp Lys Phe 180 185 190 Asn Asp Ile Pro Lys Glu Gln Arg Ala Met Ile Thr Ser Glu Gly Ala 195 200 205 Phe Lys Tyr Phe Ser Lys Gln Tyr Gly Ile Thr Pro Gly Tyr Ile Trp 210 215 220 Glu Ile Asn Thr Glu Lys Gln Gly Thr Pro Glu Gln Met Arg Gln Ala 225 230 235 240 Ile Glu Phe Val Lys Lys His Lys Leu Lys His Leu Leu Val Glu Thr 245 250 255 Ser Val Asp Lys Lys Ala Met Glu Ser Leu Ser Glu Glu Thr Lys Lys 260 265 270 Asp Ile Phe Gly Glu Val Tyr Thr Asp Ser Ile Gly Lys Glu Gly Thr 275 280 285 Lys Gly Asp Ser Tyr Tyr Lys Met Met Lys Ser Asn Ile Glu Thr Val 290 295 300 His Gly Ser Met Lys 305 9 309 PRT S. epidermidis 9 Met Lys Lys Ile Leu Ala Leu Ala Ile Ala Phe Leu Ile Ile Leu Ala 1 5 10 15 Ala Cys Gly Asn His Ser Asn His Glu His His Ser His Glu Gly Lys 20 25 30 Leu Lys Val Val Thr Thr Asn Ser Ile Leu Tyr Asp Met Val Lys Arg 35 40 45 Val Gly Gly Asn Lys Val Asp Val His Ser Ile Val Pro Val Gly Gln 50 55 60 Asp Pro His Glu Tyr Glu Val Lys Pro Lys Asp Ile Lys Ala Leu Thr 65 70 75 80 Asp Ala Asp Val Val Phe Tyr Asn Gly Leu Asn Leu Glu Thr Gly Asn 85 90 95 Gly Trp Phe Glu Lys Ala Leu Asp Gln Ala Gly Lys Ser Thr Lys Asp 100 105 110 Lys Asn Val Ile Ala Ala Ser Asn Asn Val Lys Pro Ile Tyr Leu Asn 115 120 125 Gly Glu Glu Gly Asn Lys Asn Lys Gln Asp Pro His Ala Trp Leu Ser 130 135 140 Leu Glu Asn Gly Ile Lys Tyr Val Lys Thr Ile Gln Lys Ser Leu Glu 145 150 155 160 His His Asp Lys Lys Asp Lys Ser Thr Tyr Glu Lys Gln Gly Asn Ala 165 170 175 Tyr Ile Ser Lys Leu Glu Glu Leu Asn Lys Asp Ser Lys Asn Lys Phe 180 185 190 Asp Asp Ile Pro Lys Asn Gln Arg Ala Met Met Thr Ser Glu Gly Ala 195 200 205 Phe Lys Tyr Phe Ala Gln Gln Phe Asp Val Lys Pro Gly Tyr Ile Trp 210 215 220 Glu Ile Asn Thr Glu Lys Gln Gly Thr Pro Gly Gln Met Lys Gln Ala 225 230 235 240 Ile Lys Phe Val Lys Asp Asn His Leu Lys His Leu Leu Val Glu Thr 245 250 255 Ser Val Asp Lys Lys Ala Met Gln Ser Leu Ser Glu Glu Thr Lys Lys 260 265 270 Asp Ile Tyr Gly Glu Val Phe Thr Asp Ser Ile Gly Lys Glu Gly Thr 275 280 285 Lys Gly Asp Ser Tyr Tyr Lys Met Met Lys Ser Asn Ile Asp Thr Ile 290 295 300 His Gly Ser Met Lys 305 10 233 PRT S. aureus 10 Met Lys Lys Thr Ile Met Ala Ser Ser Leu Ala Val Ala Leu Gly Val 1 5 10 15 Thr Gly Tyr Ala Ala Gly Thr Gly His Gln Ala His Ala Ala Glu Val 20 25 30 Asn Val Asp Gln Ala His Leu Val Asp Leu Ala His Asn His Gln Asp 35 40 45 Gln Leu Asn Ala Ala Pro Ile Lys Asp Gly Ala Tyr Asp Ile His Phe 50 55 60 Val Lys Asp Gly Phe Gln Tyr Asn Phe Thr Ser Asn Gly Thr Thr Trp 65 70 75 80 Ser Trp Ser Tyr Glu Ala Ala Asn Gly Gln Thr Ala Gly Phe Ser Asn 85 90 95 Val Ala Gly Ala Asp Tyr Thr Thr Ser Tyr Asn Gln Gly Ser Asp Val 100 105 110 Gln Ser Val Ser Tyr Asn Ala Gln Ser Ser Asn Ser Asn Val Glu Ala 115 120 125 Val Ser Ala Pro Thr Tyr His Asn Tyr Ser Thr Ser Thr Thr Ser Ser 130 135 140 Ser Val Arg Leu Ser Asn Gly Asn Thr Ala Gly Ala Thr Gly Ser Ser 145 150 155 160 Ala Ala Gln Ile Met Ala Gln Arg Thr Gly Val Ser Ala Ser Thr Trp 165 170 175 Ala Ala Ile Ile Ala Arg Glu Ser Asn Gly Gln Val Asn Ala Tyr Asn 180 185 190 Pro Ser Gly Ala Ser Gly Leu Phe Gln Thr Met Pro Gly Trp Gly Pro 195 200 205 Thr Asn Thr Val Asp Gln Gln Ile Asn Ala Ala Val Lys Ala Tyr Lys 210 215 220 Ala Gln Gly Leu Gly Ala Trp Gly Phe 225 230 11 235 PRT S. epidermidis 11 Met Lys Lys Thr Val Ile Ala Ser Thr Leu Ala Val Ser Leu Gly Ile 1 5 10 15 Ala Gly Tyr Gly Leu Ser Gly His Glu Ala His Ala Ser Glu Thr Thr 20 25 30 Asn Val Asp Lys Ala His Leu Val Asp Leu Ala Gln His Asn Pro Glu 35 40 45 Glu Leu Asn Ala Lys Pro Val Gln Ala Gly Ala Tyr Asp Ile His Phe 50 55 60 Val Asp Asn Gly Tyr Gln Tyr Asn Phe Thr Ser Asn Gly Ser Glu Trp 65 70 75 80 Ser Trp Ser Tyr Ala Val Ala Gly Ser Asp Ala Asp Tyr Thr Glu Ser 85 90 95 Ser Ser Asn Gln Glu Val Ser Ala Asn Thr Gln Ser Ser Asn Thr Asn 100 105 110 Val Gln Ala Val Ser Ala Pro Thr Ser Ser Glu Ser Arg Ser Tyr Ser 115 120 125 Thr Ser Thr Thr Ser Tyr Ser Ala Pro Ser His Asn Tyr Ser Ser His 130 135 140 Ser Ser Ser Val Arg Leu Ser Asn Gly Asn Thr Ala Gly Ser Val Gly 145 150 155 160 Ser Tyr Ala Ala Ala Gln Met Ala Ala Arg Thr Gly Val Ser Ala Ser 165 170 175 Thr Trp Glu His Ile Ile Ala Arg Glu Ser Asn Gly Gln Leu His Ala 180 185 190 Arg Asn Ala Ser Gly Ala Ala Gly Leu Phe Gln Thr Met Pro Gly Trp 195 200 205 Gly Ser Thr Gly Ser Val Asn Asp Gln Ile Asn Ala Ala Tyr Lys Ala 210 215 220 Tyr Lys Ala Gln Gly Leu Ser Ala Trp Gly Met 225 230 235 12 3890 PRT S. aureus 12 Met Asn Tyr Arg Asp Lys Ile Gln Lys Phe Ser Ile Arg Lys Tyr Thr 1 5 10 15 Val Gly Thr Phe Ser Thr Val Ile Ala Thr Leu Val Phe Leu Gly Phe 20 25 30 Asn Thr Ser Gln Ala His Ala Ala Glu Thr Asn Gln Pro Ala Ser Val 35 40 45 Val Lys Gln Lys Gln Gln Ser Asn Asn Glu Gln Thr Glu Asn Arg Glu 50 55 60 Ser Gln Val Gln Asn Ser Gln Asn Ser Gln Asn Ser Gln Ser Leu Ser 65 70 75 80 Ala Thr His Glu Asn Glu Gln Pro Asn Asn Ser Gln Ala Asn Leu Val 85 90 95 Asn Gln Lys Val Ala Gln Ser Ser Thr Thr Asn Asp Glu Gln Pro Ala 100 105 110 Ser Gln Asn Val Asn Thr Lys Lys Asp Ser Ala Thr Ala Ala Thr Thr 115 120 125 Gln Pro Asp Lys Glu Glu Ser Lys His Lys Gln Asn Glu Ser Gln Ser 130 135 140 Ala Asn Lys Asn Gly Asn Asp Asn Arg Ala Ala His Val Glu Asn His 145 150 155 160 Glu Ala Asn Val Val Thr Ala Ser Asp Ser Ser Asp Asn Gly Asn Val 165 170 175 Gln His Asp Arg Asn Glu Leu Gln Ala Phe Phe Asp Ala Asn Tyr His 180 185 190 Asp Tyr Arg Phe Ile Asp Arg Glu Asn Ala Asp Ser Gly Thr Phe Asn 195 200 205 Tyr Val Lys Gly Ile Phe Asp Lys Ile Asn Thr Leu Leu Gly Ser Asn 210 215 220 Asp Pro Ile Asn Asn Lys Asp Leu Gln Leu Ala Tyr Lys Glu Leu Glu 225 230 235 240 Gln Ala Val Ala Leu Ile Arg Thr Met Pro Gln Arg Gln Gln Thr Ser 245 250 255 Arg Arg Ser Asn Arg Ile Gln Thr Arg Ser Val Glu Ser Arg Ala Ala 260 265 270 Glu Pro Arg Ser Val Ser Asp Tyr Gln Asn Ala Asn Ser Ser Tyr Tyr 275 280 285 Val Glu Asn Ala Asn Asp Gly Ser Gly Tyr Pro Val Gly Thr Tyr Ile 290 295 300 Asn Ala Ser Ser Lys Gly Ala Pro Tyr Asn Leu Pro Thr Thr Pro Trp 305 310 315 320 Asn Thr Leu Lys Ala Ser Asp Ser Lys Glu Ile Ala Leu Met Thr Ala 325 330 335 Lys Gln Thr Gly Asp Gly Tyr Gln Trp Val Ile Lys Phe Asn Lys Gly 340 345 350 His Ala Pro His Gln Asn Met Ile Phe Trp Phe Ala Leu Pro Ala Asp 355 360 365 Gln Val Pro Val Gly Arg Thr Asp Phe Val Thr Val Asn Ser Asp Gly 370 375 380 Thr Asn Val Gln Trp Ser His Gly Ala Gly Ala Gly Ala Asn Lys Pro 385 390 395 400 Leu Gln Gln Met Trp Glu Tyr Gly Val Asn Asp Pro Asp Arg Ser His 405 410 415 Asp Phe Lys Ile Arg Asn Arg Ser Gly Gln Val Ile Tyr Ser Trp Pro 420 425 430 Thr Val His Val Tyr Ser Leu Glu Asp Leu Ser Arg Ala Ser Asp Tyr 435 440 445 Phe Ser Glu Ala Gly Ala Thr Pro Ala Thr Lys Ala Phe Gly Arg Gln 450 455 460 Asn Phe Glu Tyr Ile Asn Gly Gln Lys Pro Ala Glu Ser Pro Gly Val 465 470 475 480 Pro Lys Val Tyr Thr Phe Ile Gly Gln Gly Asp Ala Ser Tyr Thr Ile 485 490 495 Ser Phe Lys Thr Gln Gly Pro Thr Val Asn Lys Leu Tyr Tyr Ala Ala 500 505 510 Gly Gly Arg Ala Leu Glu Tyr Asn Gln Leu Phe Met Tyr Ser Gln Leu 515 520 525 Tyr Val Glu Ser Thr Gln Asp His Gln Gln Arg Leu Asn Gly Leu Arg 530 535 540 Gln Val Val Asn Arg Thr Tyr Arg Ile Gly Thr Thr Lys Arg Val Glu 545 550 555 560 Val Ser Gln Gly Asn Val Gln Thr Lys Lys Val Leu Glu Ser Thr Asn 565 570 575 Leu Asn Ile Asp Asp Phe Val Asp Asp Pro Leu Ser Tyr Val Lys Thr 580 585 590 Pro Ser Asn Lys Val Leu Gly Phe Tyr Pro Thr Asn Ala Asn Thr Asn 595 600 605 Ala Phe Arg Pro Gly Gly Val Gln Glu Leu Asn Glu Tyr Gln Leu Ser 610 615 620 Gln Leu Phe Thr Asp Gln Lys Leu Gln Glu Ala Ala Arg Thr Arg Asn 625 630 635 640 Pro Ile Arg Leu Met Ile Gly Phe Asp Tyr Pro Asp Gly Tyr Gly Asn 645 650 655 Ser Glu Thr Leu Val Pro Val Asn Leu Thr Val Leu Pro Glu Ile Gln 660 665 670 His Asn Ile Lys Phe Phe Lys Asn Asp Asp Thr Gln Asn Ile Ala Glu 675 680 685 Lys Pro Phe Ser Lys Gln Ala Gly His Pro Val Phe Tyr Val Tyr Ala 690 695 700 Gly Asn Gln Gly Asn Ala Ser Val Asn Leu Gly Gly Ser Val Thr Ser 705 710 715 720 Ile Gln Pro Leu Arg Ile Asn Leu Thr Ser Asn Glu Asn Phe Thr Asp 725 730 735 Lys Asp Trp Gln Ile Thr Gly Ile Pro Arg Thr Leu His Ile Glu Asn 740 745 750 Ser Thr Asn Arg Thr Asn Asn Ala Arg Glu Arg Asn Ile Glu Leu Val 755 760 765 Gly Asn Leu Leu Pro Gly Asp Tyr Phe Gly Thr Ile Arg Phe Gly Arg 770 775 780 Lys Glu Gln Leu Phe Glu Ile Arg Val Lys Pro His Thr Pro Thr Ile 785 790 795 800 Thr Thr Thr Ala Glu Gln Leu Arg Gly Thr Ala Leu Gln Lys Val Pro 805 810 815 Val Asn Ile Ser Gly Ile Pro Leu Asp Pro Ser Ala Leu Val Tyr Leu 820 825 830 Val Ala Pro Thr Asn Gln Thr Thr Asn Gly Gly Ser Glu Ala Asp Gln 835 840 845 Ile Pro Ser Gly Tyr Thr Ile Leu Ala Thr Gly Thr Pro Asp Gly Val 850 855 860 His Asn Thr Ile Thr Ile Arg Pro Gln Asp Tyr Val Val Phe Ile Pro 865 870 875 880 Pro Val Gly Lys Gln Ile Arg Ala Val Val Tyr Tyr Asn Lys Val Val 885 890 895 Ala Ser Asn Met Ser Asn Ala Val Thr Ile Leu Pro Asp Asp Ile Pro 900 905 910 Pro Thr Ile Asn Asn Pro Val Gly Ile Asn Ala Lys Tyr Tyr Arg Gly 915 920 925 Asp Glu Val Asn Phe Thr Met Gly Val Ser Asp Arg His Ser Gly Ile 930 935 940 Lys Asn Thr Thr Ile Thr Thr Leu Pro Ser Gly Trp Thr Ser Asn Leu 945 950 955 960 Thr Lys Ser Asp Asn Lys Asn Gly Ser Leu Ala Ile Thr Gly Arg Val 965 970 975 Ser Met Asn Gln Ala Phe Asn Ser Asp Ile Thr Phe Lys Val Ser Ala 980 985 990 Thr Asp Asn Val Asn Asn Thr Thr Asn Asp Ser Gln Ser Lys His Val 995 1000 1005 Ser Ile His Val Gly Lys Ile Ser Glu Asp Ala His Pro Ile Val Leu 1010 1015 1020 Gly Asn Thr Glu Lys Val Val Val Val Asn Pro Thr Ala Val Ser Asn 1025 1030 1035 1040 Asp Glu Lys Gln Ser Ile Ile Thr Ala Phe Met Asn Lys Asn Gln Asn 1045 1050 1055 Ile Arg Gly Tyr Leu Ala Ser Thr Asp Pro Val Thr Val Asp Asn Asn

1060 1065 1070 Gly Asn Val Thr Leu His Tyr Arg Asp Gly Ser Ser Thr Thr Leu Asp 1075 1080 1085 Ala Thr Asn Val Met Thr Tyr Glu Pro Val Val Lys Ser Glu Tyr Gln 1090 1095 1100 Thr Ala Asn Ala Ala Lys Thr Ala Thr Val Thr Ile Ala Lys Gly Gln 1105 1110 1115 1120 Ser Phe Asn Ile Gly Asp Ile Lys Gln Tyr Phe Thr Leu Ser Asn Gly 1125 1130 1135 Gln Ala Ile Pro Asn Gly Thr Phe Thr Asn Ile Thr Ser Asp Arg Thr 1140 1145 1150 Ile Pro Thr Ala Gln Glu Val Ser Gln Met Asn Ala Gly Thr Gln Leu 1155 1160 1165 Tyr His Ile Val Ala Ser Asn Ala Tyr His Lys Asp Thr Glu Asp Phe 1170 1175 1180 Tyr Ile Ser Leu Lys Ile Val Asp Val Lys Gln Pro Glu Gly Asp Gln 1185 1190 1195 1200 Arg Val Tyr Arg Thr Ser Thr Tyr Asp Leu Thr Thr Asp Glu Ile Ser 1205 1210 1215 Lys Val Lys Gln Ala Phe Ile Asn Ala Asn Arg Asp Val Ile Thr Leu 1220 1225 1230 Ala Glu Gly Asp Ile Ser Val Thr Asn Thr Pro Asn Gly Ala Asn Val 1235 1240 1245 Ser Thr Ile Thr Val Asn Ile Asn Lys Gly Arg Leu Thr Lys Ser Phe 1250 1255 1260 Ala Ser Asn Leu Ala Asn Met Asn Phe Leu Arg Trp Val Asn Phe Pro 1265 1270 1275 1280 Gln Asp Tyr Thr Val Thr Trp Thr Asn Ala Lys Ile Ala Asn Arg Pro 1285 1290 1295 Thr Asp Gly Gly Leu Ser Trp Ser Asp Asp His Lys Ser Leu Ile Tyr 1300 1305 1310 Arg Tyr Asp Ala Thr Leu Gly Thr Gln Ile Thr Thr Asn Asp Ile Leu 1315 1320 1325 Thr Met Leu Lys Ala Thr Thr Thr Val Pro Gly Leu Arg Asn Asn Ile 1330 1335 1340 Thr Gly Asn Glu Lys Ala Gln Ala Glu Ala Gly Gly Arg Pro Asn Tyr 1345 1350 1355 1360 Arg Thr Thr Gly Tyr Ser Gln Ser Asn Ala Thr Thr Asp Gly Gln Arg 1365 1370 1375 Gln Phe Thr Leu Asn Gly Gln Val Ile Gln Ile Leu Asp Ile Ile Asn 1380 1385 1390 Pro Ser Asn Gly Tyr Gly Gly Gln Pro Val Thr Asn Ser Asn Thr Arg 1395 1400 1405 Ala Asn His Ser Asn Ser Thr Val Val Asn Val Asn Glu Pro Ala Ala 1410 1415 1420 Asn Gly Ala Gly Ala Phe Thr Ile Asp His Val Val Lys Ser Asn Ser 1425 1430 1435 1440 Thr His Asn Ala Ser Asp Ala Val Tyr Lys Ala Gln Leu Tyr Leu Thr 1445 1450 1455 Pro Tyr Gly Pro Lys Gln Tyr Val Glu His Leu Asn Gln Asn Thr Gly 1460 1465 1470 Asn Thr Thr Asp Ala Ile Asn Ile Tyr Phe Val Pro Ser Asp Leu Val 1475 1480 1485 Asn Pro Thr Ile Ser Val Gly Asn Tyr Thr Asn His Gln Val Phe Ser 1490 1495 1500 Gly Glu Thr Phe Thr Asn Thr Ile Thr Ala Asn Asp Asn Phe Gly Val 1505 1510 1515 1520 Gln Ser Val Thr Val Pro Asn Thr Ser Gln Ile Thr Gly Thr Val Asp 1525 1530 1535 Asn Asn His Gln His Val Ser Ala Thr Ala Pro Asn Val Thr Ser Ala 1540 1545 1550 Thr Ser Lys Thr Ile Asn Leu Leu Ala Thr Asp Thr Ser Gly Asn Thr 1555 1560 1565 Ala Thr Thr Ser Phe Asn Val Thr Val Lys Pro Leu Arg Asp Lys Tyr 1570 1575 1580 Arg Val Gly Thr Ser Ser Thr Ala Ala Asn Pro Val Arg Ile Ala Asn 1585 1590 1595 1600 Ile Ser Asn Asn Ala Thr Val Ser Gln Ala Asp Gln Thr Thr Ile Ile 1605 1610 1615 Asn Ser Leu Thr Phe Thr Ser Asn Ala Pro Asn Arg Asn Tyr Ala Thr 1620 1625 1630 Ala Ser Ala Asn Glu Ile Thr Ser Lys Thr Val Ser Asn Val Ser Arg 1635 1640 1645 Thr Gly Asn Asn Ala Asn Val Thr Val Thr Val Thr His Gln Asp Gly 1650 1655 1660 Thr Thr Ser Thr Val Thr Val Pro Val Lys His Val Ile Pro Glu Ile 1665 1670 1675 1680 Val Ala His Ser His Tyr Thr Val Gln Gly Gln Asp Phe Pro Ala Gly 1685 1690 1695 Asn Gly Ser Ser Ala Ala Asp Tyr Phe Lys Leu Ser Asn Gly Ser Ala 1700 1705 1710 Ile Pro Asp Ala Thr Ile Thr Trp Val Ser Gly Gln Ala Pro Asn Lys 1715 1720 1725 Asp Asn Thr Arg Ile Gly Glu Asp Ile Thr Val Thr Ala His Ile Leu 1730 1735 1740 Ile Asp Gly Glu Thr Thr Pro Ile Thr Lys Thr Ala Thr Tyr Lys Val 1745 1750 1755 1760 Val Arg Thr Val Pro Lys His Val Phe Glu Thr Ala Arg Gly Val Leu 1765 1770 1775 Tyr Pro Gly Val Ser Asp Met Tyr Asp Ala Lys Gln Tyr Val Lys Pro 1780 1785 1790 Val Asn Asn Ser Trp Ser Thr Asn Ala Gln His Met Asn Phe Gln Phe 1795 1800 1805 Val Gly Thr Tyr Gly Pro Asn Lys Asp Val Val Gly Ile Ser Thr Arg 1810 1815 1820 Leu Ile Arg Val Thr Tyr Asp Asn Arg Gln Thr Glu Asp Leu Thr Ile 1825 1830 1835 1840 Leu Ser Lys Val Lys Pro Asp Pro Pro Arg Ile Asp Ala Asn Ser Val 1845 1850 1855 Thr Tyr Lys Ala Gly Leu Thr Asn Gln Glu Ile Lys Val Asn Asn Val 1860 1865 1870 Leu Asn Asn Ser Ser Val Lys Leu Phe Lys Ala Asp Asn Thr Pro Leu 1875 1880 1885 Asn Val Thr Asn Ile Thr His Gly Ser Gly Phe Ser Ser Val Val Thr 1890 1895 1900 Val Ser Asp Ala Leu Pro Asn Gly Gly Ile Lys Ala Lys Ser Ser Ile 1905 1910 1915 1920 Ser Met Asn Asn Val Thr Tyr Thr Thr Gln Asp Glu His Gly Gln Val 1925 1930 1935 Val Thr Val Thr Arg Asn Glu Ser Val Asp Ser Asn Asp Ser Ala Ser 1940 1945 1950 Val Thr Val Thr Pro Gln Leu Gln Ala Thr Thr Glu Gly Ala Val Phe 1955 1960 1965 Ile Lys Gly Gly Asp Gly Phe Asp Phe Gly His Val Glu Arg Phe Ile 1970 1975 1980 Gln Asn Pro Pro His Gly Ala Thr Val Ala Trp His Asp Ser Pro Asp 1985 1990 1995 2000 Thr Trp Lys Asn Thr Val Gly Asn Thr His Lys Thr Ala Val Val Thr 2005 2010 2015 Leu Pro Ser Gly Gln Gly Thr Arg Asn Val Glu Val Pro Val Lys Val 2020 2025 2030 Tyr Pro Val Ala Asn Ala Lys Ala Pro Ser Arg Asp Val Lys Gly Gln 2035 2040 2045 Asn Leu Thr His Gly Thr Asn Ala Ile Asp Tyr Ile Thr Phe Asp Pro 2050 2055 2060 Asn Thr Asn Thr Asn Gly Ile Thr Ala Ala Trp Ala Asn Arg Gln Gln 2065 2070 2075 2080 Pro Asn Asn Gln Gln Ala Gly Val Gln His Leu Asn Val Asp Val Thr 2085 2090 2095 Tyr Pro Gly Ile Ser Ala Ala Lys Arg Val Pro Val Thr Val Asn Val 2100 2105 2110 Tyr Gln Phe Glu Phe Pro Gln Thr Thr Tyr Thr Thr Thr Val Gly Gly 2115 2120 2125 Thr Leu Ala Ser Gly Thr Gln Ala Ser Gly Tyr Ala His Met Gln Asn 2130 2135 2140 Ala Ser Gly Leu Pro Thr Asp Gly Phe Thr Tyr Lys Trp Asn Arg Asp 2145 2150 2155 2160 Thr Thr Gly Thr Asn Asp Ala Asn Trp Ala Ala Met Asn Lys Pro Asn 2165 2170 2175 Thr Ala Gln Val Val Asn Ala Lys Tyr Asp Val Ile Tyr Asn Gly His 2180 2185 2190 Thr Phe Ala Thr Ser Leu Pro Ala Lys Phe Val Val Lys Asp Val Gln 2195 2200 2205 Pro Ala Lys Pro Thr Val Thr Glu Thr Ala Ala Gly Ala Ile Thr Ile 2210 2215 2220 Ala Pro Gly Ala Asn Gln Thr Val Asn Thr His Ala Gly Asn Val Thr 2225 2230 2235 2240 Thr Tyr Ala Asp Lys Leu Val Ile Lys Arg Asn Gly Asn Val Val Thr 2245 2250 2255 Thr Phe Thr Arg Arg Asn Asn Thr Ser Pro Trp Val Lys Glu Ala Ser 2260 2265 2270 Ala Asp Asn Val Thr Gly Ile Val Gly Thr Asn Asn Gly Ile Thr Val 2275 2280 2285 Ala Ala Gly Thr Phe Asn Pro Ala Asp Thr Ile Gln Val Val Ala Thr 2290 2295 2300 Gln Gly Ser Gly Glu Thr Ile Ser Asp Glu Gln Arg Ser Asp Asp Phe 2305 2310 2315 2320 Thr Val Val Ala Pro Gln Pro Asn Gln Ala Thr Thr Lys Ile Trp Gln 2325 2330 2335 Asn Gly His Ile Asp Ile Thr Pro Asn Asn Pro Ser Gly His Leu Ile 2340 2345 2350 Asn Pro Thr Gln Ala Met Asp Ile Ala Tyr Thr Glu Lys Val Gly Asn 2355 2360 2365 Gly Ala Glu His Ser Lys Thr Ile Asn Val Val Arg Gly Gln Asn Asn 2370 2375 2380 Gln Trp Thr Ile Ala Asn Lys Pro Asp Tyr Val Thr Leu Asp Ala Gln 2385 2390 2395 2400 Thr Gly Lys Val Thr Phe Asn Ala Asn Thr Ile Lys Pro Asn Ser Ser 2405 2410 2415 Ile Thr Ile Thr Pro Lys Ala Gly Thr Gly His Ser Val Ser Ser Asn 2420 2425 2430 Pro Ser Thr Leu Thr Ala Pro Ala Ala His Thr Val Asn Thr Thr Glu 2435 2440 2445 Ile Val Lys Asp Tyr Gly Ser Asn Val Thr Ala Ala Glu Ile Asn Asn 2450 2455 2460 Ala Val Gln Val Ala Asn Lys Arg Thr Ala Thr Ile Lys Asn Gly Thr 2465 2470 2475 2480 Ala Met Pro Thr Asn Leu Ala Gly Gly Ser Thr Thr Thr Ile Pro Val 2485 2490 2495 Thr Val Thr Tyr Asn Asp Gly Ser Thr Glu Glu Val Gln Glu Ser Ile 2500 2505 2510 Phe Thr Lys Ala Asp Lys Arg Glu Leu Ile Thr Ala Lys Asn His Leu 2515 2520 2525 Asp Asp Pro Val Ser Thr Glu Gly Lys Lys Pro Gly Thr Ile Thr Gln 2530 2535 2540 Tyr Asn Asn Ala Met His Asn Ala Gln Gln Gln Ile Asn Thr Ala Lys 2545 2550 2555 2560 Thr Glu Ala Gln Gln Val Ile Asn Asn Glu Arg Ala Thr Pro Gln Gln 2565 2570 2575 Val Ser Asp Ala Leu Thr Lys Val Arg Ala Ala Gln Thr Lys Ile Asp 2580 2585 2590 Gln Ala Lys Ala Leu Leu Gln Asn Lys Glu Asp Asn Ser Gln Leu Val 2595 2600 2605 Thr Ser Lys Asn Asn Leu Gln Ser Ser Val Asn Gln Val Pro Ser Thr 2610 2615 2620 Ala Gly Met Thr Gln Gln Ser Ile Asp Asn Tyr Asn Ala Lys Lys Arg 2625 2630 2635 2640 Glu Ala Glu Thr Glu Ile Thr Ala Ala Gln Arg Val Ile Asp Asn Gly 2645 2650 2655 Asp Ala Thr Ala Gln Gln Ile Ser Asp Glu Lys His Arg Val Asp Asn 2660 2665 2670 Ala Leu Thr Ala Leu Asn Gln Ala Lys His Asp Leu Thr Ala Asp Thr 2675 2680 2685 His Ala Leu Glu Gln Ala Val Gln Gln Leu Asn Arg Thr Gly Thr Thr 2690 2695 2700 Thr Gly Lys Lys Pro Ala Ser Ile Thr Ala Tyr Asn Asn Ser Ile Arg 2705 2710 2715 2720 Ala Leu Gln Ser Asp Leu Thr Ser Ala Lys Asn Ser Ala Asn Ala Ile 2725 2730 2735 Ile Gln Lys Pro Ile Arg Thr Val Gln Glu Val Gln Ser Ala Leu Thr 2740 2745 2750 Asn Val Asn Arg Val Asn Glu Arg Leu Thr Gln Ala Ile Asn Gln Leu 2755 2760 2765 Val Pro Leu Ala Asp Asn Ser Ala Leu Arg Thr Ala Lys Thr Lys Leu 2770 2775 2780 Asp Glu Glu Ile Asn Lys Ser Val Thr Thr Asp Gly Met Thr Gln Ser 2785 2790 2795 2800 Ser Ile Gln Ala Tyr Glu Asn Ala Lys Arg Ala Gly Gln Thr Glu Thr 2805 2810 2815 Thr Asn Ala Gln Asn Val Ile Asn Asn Gly Asp Ala Thr Asp Gln Gln 2820 2825 2830 Ile Ala Ala Glu Lys Thr Lys Val Glu Glu Lys Tyr Asn Ser Leu Lys 2835 2840 2845 Gln Ala Ile Ala Gly Leu Thr Pro Asp Leu Ala Pro Leu Gln Thr Ala 2850 2855 2860 Lys Thr Gln Leu Gln Asn Asp Ile Asp Gln Pro Thr Ser Thr Thr Gly 2865 2870 2875 2880 Met Thr Ser Ala Ser Val Ala Ala Phe Asn Asp Lys Leu Ser Ala Ala 2885 2890 2895 Arg Thr Lys Ile Gln Glu Ile Asp Arg Val Leu Ala Ser His Pro Asp 2900 2905 2910 Val Ala Thr Ile Arg Gln Asn Val Thr Ala Ala Asn Ala Ala Lys Thr 2915 2920 2925 Ala Leu Asp Gln Ala Arg Asn Gly Leu Thr Val Asp Lys Ala Pro Leu 2930 2935 2940 Glu Asn Ala Lys Asn Gln Leu Gln His Ser Ile Asp Thr Gln Thr Ser 2945 2950 2955 2960 Thr Thr Gly Met Thr Gln Asp Ser Ile Asn Ala Tyr Asn Ala Lys Leu 2965 2970 2975 Thr Ala Ala Arg Asn Lys Val Gln Gln Ile Asn Gln Val Leu Ala Gly 2980 2985 2990 Ser Pro Thr Val Asp Gln Ile Asn Thr Asn Thr Ser Ala Ala Asn Gln 2995 3000 3005 Ala Lys Ser Asp Leu Asp His Ala Arg Gln Ala Leu Thr Pro Asp Lys 3010 3015 3020 Ala Pro Leu Gln Asn Ala Lys Thr Gln Leu Glu Gln Ser Ile Asn Gln 3025 3030 3035 3040 Pro Thr Asp Thr Thr Gly Met Thr Thr Ala Ser Leu Asn Ala Tyr Asn 3045 3050 3055 Gln Lys Leu Gln Ala Ala Arg Gln Lys Leu Thr Glu Ile Asn Gln Val 3060 3065 3070 Leu Asn Gly Asn Pro Thr Val Gln Asn Ile Asn Asp Lys Val Ala Glu 3075 3080 3085 Ala Asn Gln Ala Lys Asp Gln Leu Asn Thr Ala Arg Gln Gly Leu Thr 3090 3095 3100 Leu Asp Arg Gln Pro Ala Leu Thr Thr Leu His Gly Ala Ser Asn Leu 3105 3110 3115 3120 Asn Gln Ala Gln Gln Asn Asn Phe Thr Gln Gln Ile Asn Ala Ala Gln 3125 3130 3135 Asn His Ala Ala Leu Glu Thr Ile Lys Ser Asn Ile Thr Ala Leu Asn 3140 3145 3150 Thr Ala Met Thr Lys Leu Lys Asp Ser Val Ala Asp Asn Asn Thr Ile 3155 3160 3165 Lys Ser Gly Gln Asn Tyr Thr Asp Ala Thr Pro Ala Asn Lys Gln Ala 3170 3175 3180 Tyr Asp Asn Ala Val Asn Ala Ala Lys Gly Val Ile Gly Glu Thr Thr 3185 3190 3195 3200 Asn Pro Thr Met Asp Val Asn Thr Val Asn Gln Lys Ala Ala Ser Val 3205 3210 3215 Lys Ser Thr Lys Asp Ala Leu Asp Gly Gln Gln Asn Leu Gln Arg Ala 3220 3225 3230 Lys Thr Glu Ala Thr Asn Ala Ile Thr His Ala Ser Asp Leu Asn Gln 3235 3240 3245 Ala Gln Lys Asn Ala Leu Thr Gln Gln Val Asn Ser Ala Gln Asn Val 3250 3255 3260 Gln Ala Val Asn Asp Ile Lys Gln Thr Thr Gln Ser Leu Asn Thr Ala 3265 3270 3275 3280 Met Thr Gly Leu Lys Arg Gly Val Ala Asn His Asn Gln Val Val Gln 3285 3290 3295 Ser Asp Asn Tyr Val Asn Ala Asp Thr Asn Lys Lys Asn Asp Tyr Asn 3300 3305 3310 Asn Ala Tyr Asn His Ala Asn Asp Ile Ile Asn Gly Asn Ala Gln His 3315 3320 3325 Pro Val Ile Thr Pro Ser Asp Val Asn Asn Ala Leu Ser Asn Val Thr 3330 3335 3340 Ser Lys Glu His Ala Leu Asn Gly Glu Ala Lys Leu Asn Ala Ala Lys 3345 3350 3355 3360 Gln Glu Ala Asn Thr Ala Leu Gly His Leu Asn Asn Leu Asn Asn Val 3365 3370 3375 Gln Arg Gln Asn Leu Gln Ser Gln Ile Asn Gly Ala His Gln Ile Asp 3380 3385 3390 Ala Val Asn Thr Ile Lys Gln Asn Ala Thr Asn Leu Asn Ser Ala Met 3395 3400 3405 Gly Asn Leu Arg Gln Ala Val Ala Asp Lys Asp Gln Val Lys Arg Thr 3410 3415 3420 Glu Asp Tyr Ala Asp Ala Asp Thr Ala Lys Gln Asn Ala Tyr Asn Ser 3425 3430 3435 3440 Ala Val Ser Ser Ala Glu Thr Ile Ile Asn Gln Thr Ala Asn Pro Thr 3445 3450 3455 Met Ser Val Asp Asp Val Asn Arg Ala Thr Ser Ala Val Thr Thr Asn 3460 3465 3470 Lys Asn Ala Leu Asn

Gly Asp Glu Lys Leu Val Gln Ser Lys Thr Asp 3475 3480 3485 Ala Ala Arg Ala Ile Asp Ala Leu Pro His Leu Asn Asn Ala Gln Lys 3490 3495 3500 Ala Asp Val Lys Ser Lys Ile Asn Ala Ala Ser Asn Ile Ala Gly Val 3505 3510 3515 3520 Asn Thr Val Lys Gln Gln Gly Thr Asp Leu Asn Thr Ala Met Gly Asn 3525 3530 3535 Leu Gln Gly Ala Ile Asn Asp Glu Gln Thr Thr Leu Asn Ser Gln Asn 3540 3545 3550 Tyr Gln Asp Ala Thr Pro Ser Lys Lys Thr Ala Tyr Thr Asn Ala Val 3555 3560 3565 Gln Ala Ala Lys Asp Ile Leu Asn Lys Ser Asn Gly Gln Asn Lys Thr 3570 3575 3580 Lys Asp Gln Val Thr Glu Ala Met Asn Gln Val Asn Ser Ala Lys Asn 3585 3590 3595 3600 Asn Leu Asp Gly Thr Arg Leu Leu Asp Gln Ala Lys Gln Thr Ala Lys 3605 3610 3615 Gln Gln Leu Asn Asn Met Thr His Leu Thr Thr Ala Gln Lys Thr Asn 3620 3625 3630 Leu Thr Asn Gln Ile Asn Ser Gly Thr Thr Val Ala Gly Val His Thr 3635 3640 3645 Val Gln Ser Asn Ala Asn Thr Leu Asp Gln Ala Met Asn Thr Leu Arg 3650 3655 3660 Gln Ser Ile Ala Asn Asn Asp Ala Thr Lys Ala Ser Glu Asp Tyr Val 3665 3670 3675 3680 Asp Ala Asn Asn Asp Lys Gln Thr Ala Tyr Asn Asn Ala Val Ala Ala 3685 3690 3695 Ala Glu Thr Ile Ile Asn Ala Asn Ser Asn Pro Glu Met Asn Pro Ser 3700 3705 3710 Thr Ile Thr Gln Lys Ala Glu Gln Val Asn Ser Ser Lys Thr Ala Leu 3715 3720 3725 Asn Gly Asp Glu Asn Leu Ala Thr Ala Lys Gln Asn Ala Lys Thr Tyr 3730 3735 3740 Leu Asn Thr Leu Thr Ser Ile Thr Asp Ala Gln Lys Asn Asn Leu Ile 3745 3750 3755 3760 Ser Gln Ile Ser Ser Ala Thr Arg Val Ser Gly Val Asp Thr Val Lys 3765 3770 3775 Gln Asn Ala Gln His Leu Asp Gln Ala Met Ala Asn Leu Gln Asn Gly 3780 3785 3790 Ile Asn Asn Glu Ser Gln Val Lys Ser Ser Glu Lys Tyr Arg Asp Ala 3795 3800 3805 Asp Thr Asn Lys Gln Gln Glu Tyr Asp Asn Ala Ile Thr Ala Ala Lys 3810 3815 3820 Ala Ile Leu Asn Lys Ser Thr Gly Pro Asn Thr Ala Gln Asn Ala Val 3825 3830 3835 3840 Glu Ala Ala Leu Gln Arg Val Asn Thr Ala Lys Asp Ala Leu Asn Gly 3845 3850 3855 Asp Ala Lys Leu Ile Ala Ala Gln Asn Ala Ala Lys Gln His Leu Gly 3860 3865 3870 Thr Leu Thr His Ile Thr Thr Ala Gln Arg Asn Asp Leu Thr Asn Gln 3875 3880 3885 Ile Ser 3890 13 6713 PRT S. aureus 13 Met Gly Asn Leu Gln Thr Ala Ile Asn Asp Lys Ser Gly Thr Leu Ala 1 5 10 15 Ser Gln Asn Phe Leu Asp Ala Asp Glu Gln Lys Arg Asn Ala Tyr Asn 20 25 30 Gln Ala Ile Ser Ala Ala Glu Thr Ile Leu Asn Lys Gln Thr Gly Pro 35 40 45 Asn Thr Ala Lys Thr Ala Val Glu Gln Ala Leu Asn Asn Val Asn Ser 50 55 60 Ala Lys His Ala Leu Asn Gly Thr Gln Asn Leu Asn Asn Ala Lys Gln 65 70 75 80 Ala Ala Ile Thr Ala Ile Asn Gly Ala Ser Asp Leu Asn Gln Lys Gln 85 90 95 Lys Asp Ala Leu Lys Ala Gln Ala Asn Gly Ala Gln Arg Val Ser Asn 100 105 110 Ala Asn Asp Val Gln Arg Asn Ala Thr Glu Leu Asn Thr Ala Met Gly 115 120 125 Gln Leu Gln His Ala Ile Ala Asp Lys Thr Asn Thr Leu Ala Ser Ser 130 135 140 Lys Tyr Val Asn Ala Asp Ser Thr Lys Gln Asn Ala Tyr Thr Thr Lys 145 150 155 160 Val Thr Asn Ala Glu His Ile Ile Ser Gly Thr Pro Thr Val Val Thr 165 170 175 Thr Pro Ser Glu Val Thr Ala Ala Ala Asn Gln Val Asn Ser Ala Lys 180 185 190 Gln Glu Leu Asn Gly Asp Glu Arg Leu Arg Val Ala Lys Gln Asn Ala 195 200 205 Asn Thr Ala Ile Asp Ala Leu Thr Gln Leu Asn Thr Pro Gln Lys Ala 210 215 220 Lys Leu Lys Glu Gln Val Gly Gln Ala Asn Arg Leu Glu Asp Val Gln 225 230 235 240 Ser Val Gln Thr Asn Gly Gln Ser Leu Asn Asn Ala Met Lys Gly Leu 245 250 255 Arg Asp Ser Ile Ala Asn Glu Thr Thr Val Lys Ala Ser Gln Asn Tyr 260 265 270 Thr Asp Ala Ser Pro Asn Asn Gln Ser Thr Tyr Asn Ser Ala Val Ser 275 280 285 Asn Ala Lys Gly Ile Ile Asn Gln Thr Asn Asn Pro Thr Met Asp Thr 290 295 300 Ser Ala Ile Thr Gln Ala Thr Thr Gln Val Asn Asn Ala Lys Asn Gly 305 310 315 320 Leu Asn Gly Ala Glu Asn Leu Arg Asn Ala Gln Asn Thr Ala Lys Gln 325 330 335 Asn Leu Asn Thr Leu Ser His Leu Thr Asn Asn Gln Lys Ser Ala Ile 340 345 350 Ser Ser Gln Ile Asp Arg Ala Gly His Val Ser Glu Val Thr Ala Ala 355 360 365 Lys Asn Ala Ala Thr Glu Leu Asn Ala Gln Met Gly Asn Leu Glu Gln 370 375 380 Ala Ile His Asp Gln Asn Thr Val Lys Gln Gly Val Asn Phe Thr Asp 385 390 395 400 Ala Asp Lys Ala Lys Arg Asp Ala Tyr Thr Asn Ala Val Ser Arg Ala 405 410 415 Glu Thr Ile Leu Asn Lys Thr Gln Gly Ala Asn Thr Ser Lys Gln Asp 420 425 430 Val Glu Ala Ala Ile Gln Asn Val Thr Ser Ala Lys Asn Ala Leu Asn 435 440 445 Gly Asp Gln Asn Val Thr Asn Ala Lys Asn Ala Ala Lys Asn Ala Leu 450 455 460 Asn Asn Leu Thr Ser Ile Asn Asn Ala Gln Lys Arg Asp Leu Thr Thr 465 470 475 480 Lys Ile Asp Gln Ala Thr Thr Val Ala Gly Val Glu Ala Val Ser Asn 485 490 495 Thr Gly Thr Gln Leu Asn Thr Ala Met Ala Asn Leu Gln Asn Gly Ile 500 505 510 Asn Asp Lys Ala Asn Thr Leu Ala Ser Glu Asn Tyr His Asp Ala Asp 515 520 525 Ser Asp Lys Lys Thr Ala Tyr Thr Gln Ala Val Thr Asn Ala Glu Asn 530 535 540 Ile Leu Asn Lys Asn Ser Gly Ser Asn Leu Asp Lys Ala Ala Val Glu 545 550 555 560 Asn Ala Leu Ser Gln Val Thr Asn Ala Lys Gly Ala Leu Asn Gly Asn 565 570 575 His Asn Leu Glu Gln Ala Lys Ser Asn Ala Asn Thr Thr Ile Asn Gly 580 585 590 Leu Gln His Leu Thr Thr Ala Gln Lys Asp Lys Leu Lys Gln Gln Val 595 600 605 Gln Gln Ala Gln Asn Val Ala Gly Val Asp Thr Val Lys Ser Ser Ala 610 615 620 Asn Thr Leu Asn Gly Ala Met Gly Thr Leu Arg Asn Ser Ile Gln Asp 625 630 635 640 Asn Thr Ala Thr Lys Asn Gly Gln Asn Tyr Leu Asp Ala Thr Glu Arg 645 650 655 Asn Lys Thr Asn Tyr Asn Asn Ala Val Asp Ser Ala Asn Gly Val Ile 660 665 670 Asn Ala Thr Ser Asn Pro Asn Met Asp Ala Asn Ala Ile Asn Gln Ile 675 680 685 Ala Thr Gln Val Thr Ser Thr Lys Asn Ala Leu Asp Gly Thr His Asn 690 695 700 Leu Thr Gln Ala Lys Gln Thr Ala Thr Asn Ala Ile Asp Gly Ala Thr 705 710 715 720 Asn Leu Asn Lys Ala Gln Lys Asp Ala Leu Lys Ala Gln Val Thr Ser 725 730 735 Ala Gln Arg Val Ala Asn Val Thr Ser Ile Gln Gln Thr Ala Asn Glu 740 745 750 Leu Asn Thr Ala Met Gly Gln Leu Gln His Gly Ile Asp Asp Glu Asn 755 760 765 Ala Thr Lys Gln Thr Gln Lys Tyr Arg Asp Ala Glu Gln Ser Lys Lys 770 775 780 Thr Ala Tyr Asp Gln Ala Val Ala Ala Ala Lys Ala Ile Leu Asn Lys 785 790 795 800 Gln Thr Gly Ser Asn Ser Asp Lys Ala Ala Val Asp Arg Ala Leu Gln 805 810 815 Gln Val Thr Ser Thr Lys Asp Ala Leu Asn Gly Asp Ala Lys Leu Ala 820 825 830 Glu Ala Lys Ala Ala Ala Arg Gln Asn Leu Gly Thr Leu Asn His Ile 835 840 845 Thr Asn Ala Gln Arg Thr Ala Leu Glu Gly Gln Ile Asn Gln Ala Thr 850 855 860 Thr Val Asp Gly Val Asn Thr Val Lys Thr Asn Ala Asn Thr Leu Asp 865 870 875 880 Gly Ala Met Asn Ser Leu Gln Gly Ala Ile Asn Asp Lys Asp Ala Thr 885 890 895 Leu Arg Asn Gln Asn Tyr Leu Asp Ala Asp Glu Ser Lys Arg Asn Ala 900 905 910 Tyr Thr Gln Ala Val Thr Ala Ala Glu Gly Ile Leu Asn Lys Gln Thr 915 920 925 Gly Gly Asn Thr Ser Lys Ala Asp Val Asp Asn Ala Leu Asn Ala Val 930 935 940 Thr Arg Ala Lys Ala Ala Leu Asn Gly Ala Glu Asn Leu Arg Asn Ala 945 950 955 960 Lys Thr Ser Ala Thr Asn Thr Ile Asn Gly Leu Pro Asn Leu Thr Gln 965 970 975 Leu Gln Lys Asp Asn Leu Lys His Gln Val Glu Gln Ala Gln Asn Val 980 985 990 Val Gly Val Asn Gly Val Lys Asp Lys Gly Asn Thr Leu Asn Thr Ala 995 1000 1005 Met Gly Ala Leu Arg Thr Ser Ile Gln Asn Asp Asn Thr Thr Lys Thr 1010 1015 1020 Ser Gln Asn Tyr Leu Asp Ala Ser Asp Ser Asn Lys Asn Asn Tyr Asn 1025 1030 1035 1040 Thr Ala Val Asn Asn Ala Asn Gly Val Ile Asn Ala Thr Asn Asn Pro 1045 1050 1055 Asn Met Asp Ala Asn Ala Ile Asn Asp Met Ala Asn Gln Val Asn Thr 1060 1065 1070 Thr Lys Ala Ala Leu Asn Gly Ala Gln Asn Leu Ala Gln Ala Lys Thr 1075 1080 1085 Asn Ala Thr Asn Thr Ile Asn Asn Ala Gln Asp Leu Asn Gln Lys Gln 1090 1095 1100 Lys Asp Ala Leu Lys Thr Gln Val Asn Asn Ala Gln Arg Val Ser Asp 1105 1110 1115 1120 Ala Asn Asn Val Gln His Thr Ala Thr Glu Leu Asn Gly Ala Met Thr 1125 1130 1135 Ala Leu Lys Ala Ala Ile Ala Asp Lys Glu Arg Thr Lys Ala Ser Gly 1140 1145 1150 Asn Tyr Val Asn Ala Asp Gln Glu Lys Arg Gln Ala Tyr Asp Ser Lys 1155 1160 1165 Val Thr Asn Ala Glu Asn Ile Ile Asn Gly Thr Pro Asn Ala Thr Leu 1170 1175 1180 Thr Val Asn Asp Val Asn Ser Ala Ala Ser Gln Val Asn Ala Ala Lys 1185 1190 1195 1200 Thr Ala Leu Asn Gly Asp Asn Asn Leu Arg Val Ala Lys Glu His Ala 1205 1210 1215 Asn Asn Thr Ile Asp Gly Leu Ala Gln Leu Asn Asn Val Gln Lys Ala 1220 1225 1230 Lys Leu Lys Glu Gln Val Gln Ser Ala Thr Thr Leu Asp Gly Val Gln 1235 1240 1245 Thr Val Lys Asn Ser Ser Gln Thr Leu Asn Thr Ala Met Lys Gly Leu 1250 1255 1260 Arg Asp Ser Ile Ala Asn Glu Ala Thr Ile Lys Ala Gly Gln Asn Tyr 1265 1270 1275 1280 Thr Asp Ala Ser Pro Asn Asn Arg Asn Glu Tyr Asp Ser Ala Val Thr 1285 1290 1295 Ala Ala Lys Ala Ile Ile Asn Gln Thr Ser Asn Pro Thr Met Glu Pro 1300 1305 1310 Asn Thr Ile Thr Gln Ala Thr Ser Gln Val Thr Thr Lys Glu His Ala 1315 1320 1325 Leu Asn Gly Ala Gln Asn Leu Ala Gln Ala Lys Thr Thr Ala Lys Asn 1330 1335 1340 Asn Leu Asn Asn Leu Thr Ser Ile Asn Asn Ala Gln Lys Asp Ala Leu 1345 1350 1355 1360 Thr Arg Asn Ile Asp Gly Ala Thr Thr Val Ala Gly Val Asn Gln Glu 1365 1370 1375 Thr Ala Lys Ala Thr Glu Leu Asn Asn Ala Met His Ser Leu Gln Asn 1380 1385 1390 Gly Ile Asn Asp Glu Thr Gln Thr Lys Gln Thr Gln Lys Tyr Leu Asp 1395 1400 1405 Ala Glu Pro Ser Lys Lys Ser Ala Tyr Asp Gln Ala Val Asn Ala Ala 1410 1415 1420 Lys Ala Ile Leu Thr Lys Ala Ser Gly Gln Asn Val Asp Lys Ala Ala 1425 1430 1435 1440 Val Glu Gln Ala Leu Gln Asn Val Asn Ser Thr Lys Thr Ala Leu Asn 1445 1450 1455 Gly Asp Ala Lys Leu Asn Glu Ala Lys Ala Ala Ala Lys Gln Thr Leu 1460 1465 1470 Gly Thr Leu Thr His Ile Asn Asn Ala Gln Arg Asn Ala Leu Asp Asn 1475 1480 1485 Glu Ile Thr Gln Ala Thr Asn Val Glu Gly Val Asn Thr Val Lys Ala 1490 1495 1500 Lys Ala Gln Gln Leu Asp Gly Ala Met Gly Gln Leu Glu Thr Ser Ile 1505 1510 1515 1520 Arg Asp Lys Asp Thr Thr Leu Gln Ser Gln Asn Tyr Gln Asp Ala Asp 1525 1530 1535 Asp Ala Lys Arg Thr Ala Tyr Ser Gln Ala Val Asn Ala Ala Ala Thr 1540 1545 1550 Ile Leu Asn Lys Thr Ala Gly Gly Asn Thr Pro Lys Ala Asp Val Glu 1555 1560 1565 Arg Ala Met Gln Ala Val Thr Gln Ala Asn Thr Ala Leu Asn Gly Ile 1570 1575 1580 Gln Asn Leu Glu Arg Ala Lys Gln Ala Ala Asn Thr Ala Ile Thr Asn 1585 1590 1595 1600 Ala Ser Asp Leu Asn Thr Lys Gln Lys Glu Ala Leu Lys Ala Gln Val 1605 1610 1615 Thr Ser Ala Gly Arg Val Ser Ala Ala Asn Gly Val Glu His Thr Ala 1620 1625 1630 Thr Glu Leu Asn Thr Ala Met Thr Ala Leu Lys Arg Ala Ile Ala Asp 1635 1640 1645 Lys Ala Asp Thr Lys Ala Ser Gly Asn Tyr Val Asn Ala Asp Ala Asn 1650 1655 1660 Lys Arg Gln Ala Tyr Asp Glu Lys Val Thr Ala Ala Glu His Ile Val 1665 1670 1675 1680 Ser Gly Thr Pro Thr Pro Thr Leu Thr Pro Ser Asp Val Thr Asn Ala 1685 1690 1695 Ala Thr Gln Val Thr Asn Ala Lys Thr Gln Leu Asn Gly Asn His Asn 1700 1705 1710 Leu Glu Val Ala Lys Gln Asn Ala Asn Thr Ala Ile Asp Gly Leu Thr 1715 1720 1725 Ser Leu Asn Gly Pro Gln Lys Ala Lys Leu Lys Glu Gln Val Gly Gln 1730 1735 1740 Ala Thr Thr Leu Pro Asn Val Gln Thr Val Arg Asp Asn Ala Gln Thr 1745 1750 1755 1760 Leu Asn Thr Ala Met Lys Gly Leu Arg Asp Ser Ile Ala Asn Glu Ala 1765 1770 1775 Thr Ile Lys Ala Gly Gln Asn Tyr Thr Asp Ala Ser Gln Asn Lys Gln 1780 1785 1790 Asn Asp Tyr Asn Asn Ala Val Thr Ala Ala Lys Ala Ile Ile Gly Gln 1795 1800 1805 Thr Thr Ser Pro Ser Met Ile Ala Gln Glu Ile Asn Gln Ala Lys Asp 1810 1815 1820 Gln Val Thr Ala Lys Gln Gln Ala Leu Asn Gly Gln Glu Asn Leu Arg 1825 1830 1835 1840 Thr Ala Gln Thr Asn Ala Lys Gln His Leu Asn Gly Leu Ser Asp Leu 1845 1850 1855 Thr Asn Ala Gln Lys Asp Ala Ala Lys Arg Gln Ile Glu Gly Ala Thr 1860 1865 1870 His Val Asn Glu Val Thr Gln Ala Gln Asn Asn Ala Asp Ala Leu Asn 1875 1880 1885 Thr Ala Met Thr Asn Leu Lys Asn Gly Ile Gln Asp Gln Asn Thr Ile 1890 1895 1900 Lys Gln Gly Val Asn Phe Thr Asp Ala Asp Glu Ala Lys Arg Asn Ala 1905 1910 1915 1920 Tyr Thr Asn Ala Val Thr Gln Ala Glu Gln Ile Leu Asn Lys Ala Gln 1925 1930 1935 Gly Pro Asn Thr Ala Lys Asp Gly Val Glu Thr Ala Leu Gln Asn Val 1940 1945 1950 Gln Arg Ala Lys Asn Glu Leu Asn Gly Asn Gln Asn Val Ala Asn Ala 1955 1960 1965 Lys Thr Thr Ala Lys Asn Ala Leu Asn Asn Leu Thr Ser Ile Asn Asn 1970 1975 1980 Ala Gln Lys Ala Ala Leu Lys Ser Gln Ile Glu Gly Ala Thr Thr Val 1985 1990 1995 2000 Ala Gly Val Asn Gln Val Ser Thr Met Ala Ser Glu

Leu Asn Thr Ala 2005 2010 2015 Met Ser Asn Leu Gln Arg Gly Ile Asn Asp Glu Ala Ala Thr Lys Ala 2020 2025 2030 Ala Gln Lys Tyr Thr Glu Ala Asp Arg Asp Lys Gln Thr Ala Tyr Asn 2035 2040 2045 Asp Ala Val Thr Ala Ala Lys Thr Leu Leu Asp Lys Thr Ala Gly Ser 2050 2055 2060 Asn Asp Asn Lys Val Ala Val Glu Gln Ala Leu Gln Arg Val Asn Thr 2065 2070 2075 2080 Ala Lys Thr Ala Leu Asn Gly Asp Ala Arg Leu Asn Glu Ala Lys Asn 2085 2090 2095 Thr Ala Lys Gln Gln Leu Ala Thr Met Ser His Leu Thr Asn Ala Gln 2100 2105 2110 Lys Ala Asn Leu Thr Glu Gln Ile Glu Arg Gly Thr Thr Val Ala Gly 2115 2120 2125 Val Gln Gly Ile Gln Ala Asn Ala Gly Thr Leu Asn Gln Ala Met Asn 2130 2135 2140 Gln Leu Arg Gln Ser Ile Ala Ser Lys Asp Ala Thr Lys Ser Ser Glu 2145 2150 2155 2160 Asp Tyr Gln Asp Ala Asn Ala Asp Leu Gln Asn Ala Tyr Asn Asp Ala 2165 2170 2175 Val Thr Asn Ala Glu Gly Ile Ile Ser Ala Thr Asn Asn Pro Glu Met 2180 2185 2190 Asn Pro Asp Thr Ile Asn Gln Lys Ala Ser Gln Val Asn Ser Ala Lys 2195 2200 2205 Ser Ala Leu Asn Gly Asp Glu Lys Leu Ala Ala Val Lys Gln Thr Ala 2210 2215 2220 Lys Ser Asp Ile Gly Arg Leu Thr Asp Leu Asn Asn Ala Gln Arg Thr 2225 2230 2235 2240 Ala Ala Asn Ala Glu Val Asp Gln Ala Pro Asn Leu Ala Ala Val Thr 2245 2250 2255 Ala Ala Lys Asn Lys Ala Thr Ser Leu Asn Thr Ala Met Gly Asn Leu 2260 2265 2270 Lys His Ala Leu Ala Glu Lys Asp Asn Thr Lys Arg Ser Val Asn Tyr 2275 2280 2285 Thr Asp Ala Asp Gln Pro Lys Gln Gln Ala Tyr Asp Thr Ala Val Thr 2290 2295 2300 Gln Ala Glu Ala Ile Thr Asn Ala Asn Gly Ser Asn Ala Asn Glu Thr 2305 2310 2315 2320 Gln Val Gln Ala Ala Leu Asn Gln Leu Asn Gln Ala Lys Asn Asp Leu 2325 2330 2335 Asn Gly Asp Asn Lys Val Ala Gln Ala Lys Glu Thr Ala Lys Arg Ala 2340 2345 2350 Leu Ala Ser Tyr Ser Asn Leu Asn Asn Ala Gln Ser Thr Ala Ala Thr 2355 2360 2365 Ser Gln Ile Asp Asn Ala Thr Thr Val Ala Asp Val Thr Ala Ala Gln 2370 2375 2380 Asn Thr Ala Asn Glu Leu Asn Thr Ala Met Gly Gln Leu Gln Asn Gly 2385 2390 2395 2400 Ile Asn Asp Gln Asn Thr Val Lys Gln Gln Val Asn Phe Thr Asp Ala 2405 2410 2415 Asp Gln Gly Lys Lys Asp Ala Tyr Thr Asn Ala Val Thr Asn Ala Gln 2420 2425 2430 Gly Ile Leu Asp Lys Ala Asn Gly Gln Asn Met Thr Lys Ala Gln Val 2435 2440 2445 Glu Ala Ala Leu Asn Gln Val Thr Thr Ala Lys Asn Ala Leu Asn Gly 2450 2455 2460 Asp Ala Asn Val Arg Gln Ala Lys Ser Asp Ala Lys Ala Asn Leu Gly 2465 2470 2475 2480 Thr Leu Thr His Leu Asn Asn Ala Gln Lys Gln Asp Leu Thr Ser Gln 2485 2490 2495 Ile Glu Gly Ala Thr Thr Val Asn Gly Val Asn Ser Val Lys Thr Lys 2500 2505 2510 Ala Gln Asp Leu Asp Gly Ala Met Gln Arg Leu Glu Ser Ala Ile Ala 2515 2520 2525 Asn Lys Asp Gln Thr Lys Ala Ser Glu Asn Tyr Ile Asp Ala Asp Pro 2530 2535 2540 Thr Lys Lys Thr Ala Phe Asp Asn Ala Ile Thr Gln Ala Glu Ser Tyr 2545 2550 2555 2560 Leu Asn Lys Asp His Gly Thr Asn Lys Asp Lys Gln Ala Val Glu Gln 2565 2570 2575 Ala Ile Gln Ser Val Thr Ser Thr Glu Asn Ala Leu Asn Gly Asp Ala 2580 2585 2590 Asn Leu Gln Cys Ala Lys Thr Glu Ala Thr Gln Ala Ile Asp Asn Leu 2595 2600 2605 Thr Gln Leu Asn Thr Pro Gln Lys Thr Ala Leu Lys Gln Gln Val Asn 2610 2615 2620 Ala Ala Gln Arg Val Ser Gly Val Thr Asp Leu Lys Asn Ser Ala Thr 2625 2630 2635 2640 Ser Leu Asn Asn Ala Met Asp Gln Leu Lys Gln Ala Ile Gly Asp His 2645 2650 2655 Asp Thr Ile Val Ala Gly Gly Asn Tyr Thr Asn Ala Ser Pro Asp Lys 2660 2665 2670 Gln Gly Ala Tyr Thr Asp Ala Tyr Asn Ala Ala Lys Asn Ile Val Asn 2675 2680 2685 Gly Ser Pro Asn Val Ile Thr Asn Ala Ala Asp Val Thr Ala Ala Thr 2690 2695 2700 Gln Arg Val Asn Asn Ala Glu Thr Ser Leu Asn Gly Asp Thr Asn Leu 2705 2710 2715 2720 Ala Thr Ala Lys Gln Gln Ala Lys Asp Ala Leu Arg Gln Met Thr His 2725 2730 2735 Leu Ser Asp Ala Gln Lys Gln Ser Ile Thr Gly Gln Ile Asp Ser Ala 2740 2745 2750 Thr Gln Val Thr Gly Val Gln Ser Val Lys Asp Asn Ala Thr Asn Leu 2755 2760 2765 Asp Asn Ala Met Asn Gln Leu Arg Asn Ser Ile Ala Asn Lys Asp Glu 2770 2775 2780 Val Lys Ala Ser Gln Pro Tyr Val Asp Ala Asp Thr Asp Lys Gln Asn 2785 2790 2795 2800 Ala Tyr Asn Thr Ala Val Thr Ser Ala Glu Asn Ile Ile Asn Ala Thr 2805 2810 2815 Ser Gln Pro Thr Leu Asp Pro Ser Ala Val Thr Gln Ala Ala Asn Gln 2820 2825 2830 Val Asn Thr Asn Lys Thr Ala Leu Asn Gly Ala Gln Asn Leu Ala Asn 2835 2840 2845 Lys Lys Gln Glu Thr Thr Ala Asn Ile Asn Arg Leu Ser His Leu Asn 2850 2855 2860 Asn Ala Gln Lys Gln Asp Leu Asn Thr Gln Val Thr Asn Ala Pro Asn 2865 2870 2875 2880 Ile Ser Thr Val Asn Gln Val Lys Thr Lys Ala Glu Gln Leu Asp Gln 2885 2890 2895 Ala Met Glu Arg Leu Ile Asn Gly Ile Gln Asp Lys Asp Gln Val Lys 2900 2905 2910 Gln Ser Val Asn Phe Thr Asp Ala Asp Pro Glu Lys Gln Thr Ala Tyr 2915 2920 2925 Asn Asn Ala Val Thr Ala Ala Glu Asn Ile Ile Asn Gln Ala Asn Gly 2930 2935 2940 Thr Asn Ala Asn Gln Ser Gln Val Glu Ala Ala Leu Ser Thr Val Thr 2945 2950 2955 2960 Thr Thr Lys Gln Ala Leu Asn Gly Asp Arg Lys Val Thr Asp Ala Lys 2965 2970 2975 Asn Asn Ala Asn Gln Thr Leu Ser Thr Leu Asp Asn Leu Asn Asn Ala 2980 2985 2990 Gln Lys Gly Ala Val Thr Gly Asn Ile Asn Gln Ala His Thr Val Ala 2995 3000 3005 Glu Val Thr Gln Ala Ile Gln Thr Ala Gln Glu Leu Asn Thr Ala Met 3010 3015 3020 Gly Asn Leu Lys Asn Ser Leu Asn Asp Lys Asp Thr Thr Leu Gly Ser 3025 3030 3035 3040 Gln Asn Phe Ala Asp Ala Asp Pro Glu Lys Lys Asn Ala Tyr Asn Glu 3045 3050 3055 Ala Val Arg Asn Ala Glu Asn Ile Leu Asn Lys Ser Thr Gly Thr Asn 3060 3065 3070 Val Pro Lys Asp Gln Val Glu Ala Ala Met Asn Gln Val Asn Thr Thr 3075 3080 3085 Lys Ala Ala Leu Asn Gly Thr Gln Asn Leu Glu Lys Ala Lys Gln His 3090 3095 3100 Ala Asn Thr Ala Ile Asp Gly Leu Ser His Leu Thr Asn Ala Gln Lys 3105 3110 3115 3120 Glu Ala Leu Lys Gln Leu Val Gln Gln Ser Thr Thr Val Ala Glu Ala 3125 3130 3135 Gln Gly Asn Glu Gln Lys Ala Asn Asn Val Asp Ala Ala Met Asp Lys 3140 3145 3150 Leu Arg Gln Ser Ile Ala Asp Asn Ala Thr Thr Lys Gln Asn Gln Asn 3155 3160 3165 Tyr Thr Asp Ala Ser Pro Asn Lys Lys Asp Ala Tyr Asn Asn Ala Val 3170 3175 3180 Thr Thr Ala Gln Gly Ile Ile Asp Gln Thr Thr Asn Pro Ser Leu Asp 3185 3190 3195 3200 Pro Thr Val Ile Asn Gln Ala Ala Gly Gln Val Ser Thr Ser Lys Asn 3205 3210 3215 Ala Leu Asn Gly Asn Glu Asn Leu Glu Ala Ala Lys Gln Gln Ala Thr 3220 3225 3230 Gln Ser Leu Gly Ser Leu Asp Asn Leu Asn Asn Ala Gln Lys Gln Ala 3235 3240 3245 Val Thr Asn Gln Ile Asn Gly Ala His Thr Val Asp Glu Ala Asn Gln 3250 3255 3260 Ile Lys Gln Asn Ala Gln Asn Leu Asn Thr Ala Met Gly Asn Leu Lys 3265 3270 3275 3280 Gln Ala Ile Ala Asp Lys Asp Ala Thr Lys Ala Thr Val Asn Phe Thr 3285 3290 3295 Asp Ala Asp Gln Ala Lys Gln Gln Ala Tyr Asn Thr Ala Val Thr Asn 3300 3305 3310 Ala Glu Asn Ile Ile Ser Lys Ala Asn Gly Gly Asn Ala Thr Gln Thr 3315 3320 3325 Glu Val Glu Gln Ala Ile Gln Gln Val Asn Ala Ala Lys Gln Ala Leu 3330 3335 3340 Asn Gly Asn Ala Asn Val Gln His Ala Lys Asp Glu Ala Thr Ala Leu 3345 3350 3355 3360 Ile Asn Asn Ser Asn Asp Leu Asn Gln Ala Gln Lys Asp Ala Leu Lys 3365 3370 3375 Gln Gln Val Gln Asn Ala Thr Thr Val Ala Gly Val Asn Asn Val Lys 3380 3385 3390 Gln Thr Ala Gln Glu Leu Asn Asn Ala Met Thr Gln Leu Lys Gln Gly 3395 3400 3405 Ile Ala Asp Lys Glu Gln Thr Lys Ala Asp Gly Asn Phe Val Asn Ala 3410 3415 3420 Asp Ser Asp Lys Gln Asn Ala Tyr Asn Gln Ala Val Ala Lys Ala Glu 3425 3430 3435 3440 Ala Leu Ile Ser Gly Thr Pro Asp Val Val Val Thr Pro Ser Glu Ile 3445 3450 3455 Thr Ala Ala Leu Asn Lys Val Thr Gln Ala Lys Asn Asp Leu Asn Gly 3460 3465 3470 Asn Thr Asn Leu Ala Thr Ala Lys Gln Asn Val Gln His Ala Ile Asp 3475 3480 3485 Gln Leu Pro Asn Leu Asn Gln Ala Gln Arg Asp Glu Tyr Ser Lys Gln 3490 3495 3500 Ile Thr Gln Ala Thr Leu Val Pro Asn Val Asn Ala Ile Gln Gln Ala 3505 3510 3515 3520 Ala Thr Thr Leu Asn Asp Ala Met Thr Gln Leu Lys Gln Gly Ile Ala 3525 3530 3535 Asn Lys Ala Gln Ile Lys Gly Ser Glu Asn Tyr His Asp Ala Asp Thr 3540 3545 3550 Asp Lys Gln Thr Ala Tyr Asp Asn Ala Val Thr Lys Ala Glu Glu Leu 3555 3560 3565 Leu Lys Gln Thr Thr Asn Pro Thr Met Asp Pro Asn Thr Ile Gln Gln 3570 3575 3580 Ala Leu Thr Lys Val Asn Asp Thr Asn Gln Ala Leu Asn Gly Asn Gln 3585 3590 3595 3600 Lys Leu Ala Asp Ala Lys Gln Asp Ala Lys Thr Thr Leu Gly Thr Leu 3605 3610 3615 Asp His Leu Asn Asp Ala Gln Lys Gln Ala Leu Thr Thr Gln Val Glu 3620 3625 3630 Gln Ala Pro Asp Ile Ala Thr Val Asn Asn Val Lys Gln Asn Ala Gln 3635 3640 3645 Asn Leu Asn Asn Ala Met Thr Asn Leu Asn Asn Ala Leu Gln Asp Lys 3650 3655 3660 Thr Glu Thr Leu Asn Ser Ile Asn Phe Thr Asp Ala Asp Gln Ala Lys 3665 3670 3675 3680 Lys Asp Asp Tyr Thr Asn Ala Val Ser His Ala Glu Gly Ile Leu Ser 3685 3690 3695 Lys Ala Asn Gly Ser Asn Ala Ser Gln Thr Glu Val Glu Gln Ala Met 3700 3705 3710 Gln Arg Val Asn Glu Ala Lys Gln Ala Leu Asn Gly Asn Asp Asn Val 3715 3720 3725 Gln Arg Ala Lys Asp Ala Ala Lys Gln Val Ile Thr Asn Ala Asn Asp 3730 3735 3740 Leu Asn Gln Ala Gln Lys Asp Ala Leu Lys Gln Gln Val Asp Ala Ala 3745 3750 3755 3760 Gln Thr Val Ala Asn Val Asn Thr Ile Lys Gln Thr Ala Gln Asp Leu 3765 3770 3775 Asn Gln Ala Met Thr Gln Leu Lys Gln Gly Ile Ala Asp Lys Asp Gln 3780 3785 3790 Thr Lys Ala Asn Gly Asn Phe Val Asn Ala Asp Thr Asp Lys Gln Asn 3795 3800 3805 Ala Tyr Asn Asn Ala Val Ala His Ala Glu Gln Ile Ile Ser Gly Thr 3810 3815 3820 Pro Asn Ala Asn Val Asp Pro Gln Gln Val Ala Gln Ala Leu Gln Gln 3825 3830 3835 3840 Val Asn Gln Ala Lys Gly Asp Leu Asn Gly Asn His Asn Leu Gln Val 3845 3850 3855 Ala Lys Asp Asn Ala Asn Thr Ala Ile Asp Gln Leu Pro Asn Leu Asn 3860 3865 3870 Gln Pro Gln Lys Thr Ala Leu Lys Asp Gln Val Ser His Ala Glu Leu 3875 3880 3885 Val Thr Gly Val Asn Ala Ile Lys Gln Asn Ala Asp Ala Leu Asn Asn 3890 3895 3900 Ala Met Gly Thr Leu Lys Gln Gln Ile Gln Ala Asn Ser Gln Val Pro 3905 3910 3915 3920 Gln Ser Val Asp Phe Thr Gln Ala Asp Gln Asp Lys Gln Gln Ala Tyr 3925 3930 3935 Asn Asn Ala Ala Asn Gln Ala Gln Gln Ile Ala Asn Gly Thr Pro Thr 3940 3945 3950 Pro Val Leu Ala Pro Asp Thr Val Thr Lys Ala Val Thr Thr Met Asn 3955 3960 3965 Gln Ala Lys Asp Ala Leu Asn Gly Asp Glu Lys Leu Ala Gln Ala Lys 3970 3975 3980 Gln Asp Ala Leu Ala Asn Leu Asp Thr Leu Arg Asp Leu Asn Gln Pro 3985 3990 3995 4000 Gln Arg Asp Ala Leu Arg Asn Gln Ile Asn Gln Ala Gln Ala Leu Ala 4005 4010 4015 Thr Val Glu Gln Thr Lys Gln Asn Ala Gln Asn Val Asn Thr Ala Met 4020 4025 4030 Gly Asn Leu Lys Gln Gly Ile Ala Asn Lys Asp Thr Val Lys Ala Ser 4035 4040 4045 Glu Asn Tyr His Asp Ala Asp Val Asp Lys Gln Thr Ala Tyr Thr Asn 4050 4055 4060 Ala Val Ser Gln Ala Glu Gly Ile Ile Asn Gln Thr Thr Asn Pro Thr 4065 4070 4075 4080 Leu Asn Pro Asp Asp Ile Thr Arg Ala Leu Thr Gln Val Thr Asp Ala 4085 4090 4095 Lys Asn Ser Leu Asn Gly Glu Ala Lys Leu Ala Thr Glu Lys Gln Asn 4100 4105 4110 Ala Lys Asp Ala Val Ser Gly Met Thr His Leu Asn Asp Ala Gln Lys 4115 4120 4125 Gln Ala Leu Lys Gly Gln Ile Asp Gln Ser Pro Glu Ile Ala Thr Val 4130 4135 4140 Asn Gln Val Lys Gln Thr Ala Thr Ser Leu Asp Gln Ala Met Asp Gln 4145 4150 4155 4160 Leu Ser Gln Ala Ile Asn Asp Lys Asp Gln Ile Leu Ala Asp Gly Asn 4165 4170 4175 Tyr Leu Asn Ala Asp Pro Asp Lys Gln Asn Ala Tyr Lys Gln Ala Val 4180 4185 4190 Ala Lys Ala Glu Ala Leu Leu Asn Lys Gln Ser Gly Thr Asn Glu Val 4195 4200 4205 Gln Ala Gln Val Glu Ser Ile Thr Asn Glu Val Asn Ala Ala Lys Gln 4210 4215 4220 Ala Leu Asn Gly Asn Asp Asn Leu Ala Asn Ala Lys Gln Gln Ala Lys 4225 4230 4235 4240 Gln Gln Leu Ala Asn Leu Thr His Leu Asn Asp Ala Gln Lys Gln Ser 4245 4250 4255 Phe Glu Ser Gln Ile Thr Gln Ala Pro Leu Val Thr Asp Val Thr Thr 4260 4265 4270 Ile Asn Gln Lys Ala Gln Thr Leu Asp His Ala Met Glu Leu Leu Arg 4275 4280 4285 Asn Ser Val Ala Asp Asn Gln Thr Thr Leu Ala Ser Glu Asp Tyr His 4290 4295 4300 Asp Ala Thr Ala Gln Arg Gln Asn Asp Tyr Asn Lys Ala Val Thr Ala 4305 4310 4315 4320 Ala Asn Asn Ile Ile Asn Gln Thr Thr Ser Pro Thr Met Asn Pro Asp 4325 4330 4335 Asp Val Asn Gly Ala Thr Thr Gln Val Asn Asn Thr Lys Val Ala Leu 4340 4345 4350 Asp Gly Asp Glu Asn Leu Ala Ala Ala Lys Gln Gln Ala Asn Asn Arg 4355 4360 4365 Leu Asp Gln Leu Asp His Leu Asn Asn Ala Gln Lys Gln Gln Leu Gln 4370 4375 4380 Ser Gln Ile Thr Gln Ser Ser Asp Ile Ala Ala Val Asn Gly His Lys 4385 4390 4395 4400 Gln Thr Ala Glu Ser Leu Asn Thr Ala Met Gly Asn Leu Ile Asn Ala 4405 4410

4415 Ile Ala Asp His Gln Ala Val Glu Gln Arg Gly Asn Phe Ile Asn Ala 4420 4425 4430 Asp Thr Asp Lys Gln Thr Ala Tyr Asn Thr Ala Val Asn Glu Ala Ala 4435 4440 4445 Ala Met Ile Asn Lys Gln Thr Gly Gln Asn Ala Asn Gln Thr Glu Val 4450 4455 4460 Glu Gln Ala Ile Thr Lys Val Gln Thr Thr Leu Gln Ala Leu Asn Gly 4465 4470 4475 4480 Asp His Asn Leu Gln Val Ala Lys Thr Asn Ala Thr Gln Ala Ile Asp 4485 4490 4495 Val Leu Thr Ser Leu Asn Asp Pro Gln Lys Thr Ala Leu Lys Asp Gln 4500 4505 4510 Val Thr Ala Ala Thr Leu Val Thr Ala Val His Gln Ile Glu Gln Asn 4515 4520 4525 Ala Asn Thr Leu Asn Gln Ala Met His Gly Leu Arg Gln Ser Ile Gln 4530 4535 4540 Asp Asn Ala Ala Thr Lys Ala Asn Ser Lys Tyr Ile Asn Glu Asp Gln 4545 4550 4555 4560 Pro Glu Gln Gln Asn Tyr Asp Gln Ala Val Gln Ala Ala Asn Asn Ile 4565 4570 4575 Ile Asn Glu Gln Thr Ala Thr Leu Asp Asn Asn Ala Ile Asn Gln Val 4580 4585 4590 Ala Ala Thr Val Asn Thr Thr Lys Ala Ala Leu His Gly Asp Val Lys 4595 4600 4605 Leu Gln Asn Asp Lys Asp His Ala Lys Gln Thr Val Ser Gln Leu Ala 4610 4615 4620 His Leu Asn Asn Ala Gln Lys His Met Glu Asp Thr Leu Ile Asp Ser 4625 4630 4635 4640 Glu Thr Thr Arg Thr Ala Val Lys Gln Asp Leu Thr Glu Val Gln Ala 4645 4650 4655 Leu Asp Gln Leu Met Asp Ala Leu Gln Gln Ser Ile Ala Asp Lys Asp 4660 4665 4670 Ala Thr Arg Ala Ser Ser Ala Tyr Val Asn Ala Glu Pro Asn Lys Lys 4675 4680 4685 Gln Ala Tyr Asp Glu Ala Val Gln Asn Ala Glu Ser Ile Ile Ala Gly 4690 4695 4700 Leu Asn Asn Pro Thr Ile Asn Lys Gly Asn Val Ser Ser Ala Thr Gln 4705 4710 4715 4720 Ala Val Ile Ser Ser Lys Asn Ala Leu Asp Gly Val Glu Arg Leu Ala 4725 4730 4735 Gln Asp Lys Gln Thr Ala Gly Asn Ser Leu Asn His Leu Asp Gln Leu 4740 4745 4750 Thr Pro Ala Gln Gln Gln Ala Leu Glu Asn Gln Ile Asn Asn Ala Thr 4755 4760 4765 Thr Cys Asp Lys Val Ala Glu Ile Ile Ala Gln Ala Gln Ala Leu Asn 4770 4775 4780 Glu Ala Met Lys Ala Leu Lys Glu Ser Ile Lys Asp Gln Pro Gln Thr 4785 4790 4795 4800 Glu Ala Ser Ser Lys Phe Ile Asn Glu Asp Gln Ala Gln Lys Asp Ala 4805 4810 4815 Tyr Thr Gln Ala Val Gln His Ala Lys Asp Leu Ile Asn Lys Thr Thr 4820 4825 4830 Asp Pro Thr Leu Ala Lys Ser Ile Ile Asp Gln Ala Thr Gln Ala Val 4835 4840 4845 Thr Asp Ala Lys Asn Asn Leu His Gly Asp Gln Lys Leu Ala Gln Asp 4850 4855 4860 Lys Gln Arg Ala Thr Glu Thr Leu Asn Asn Leu Ser Asn Leu Asn Thr 4865 4870 4875 4880 Pro Gln Arg Gln Ala Leu Glu Asn Gln Ile Asn Asn Ala Ala Thr Arg 4885 4890 4895 Gly Glu Val Ala Gln Lys Leu Thr Glu Ala Gln Ala Leu Asn Gln Ala 4900 4905 4910 Met Glu Ala Leu Arg Asn Ser Ile Gln Asp Gln Gln Gln Thr Glu Ser 4915 4920 4925 Gly Ser Lys Phe Ile Asn Glu Asp Lys Pro Gln Lys Asp Ala Tyr Gln 4930 4935 4940 Ala Ala Val Gln Asn Ala Lys Asp Leu Ile Asn Gln Thr Gly Asn Pro 4945 4950 4955 4960 Thr Leu Asp Lys Ala Gln Val Glu Gln Leu Thr His Ala Phe Lys Gln 4965 4970 4975 Ala Lys Asp Asn Leu His Gly Asp Gln Lys Leu Ala Asp Asp Lys Gln 4980 4985 4990 His Ala Val Thr Asp Leu Asn Gln Leu Asn Gly Leu Asn Asn Pro Gln 4995 5000 5005 Arg Gln Ala Leu Glu Ser Gln Ile Asn Asn Ala Ala Thr Arg Gly Glu 5010 5015 5020 Val Ala Gln Lys Leu Ala Glu Ala Lys Ala Leu Asp Gln Ala Met Gln 5025 5030 5035 5040 Ala Leu Arg Asn Ser Ile Gln Asp Gln Gln Gln Thr Glu Ala Gly Ser 5045 5050 5055 Lys Phe Ile Asn Glu Asp Lys Pro Gln Lys Asp Ala Tyr Gln Ala Ala 5060 5065 5070 Val Gln Asn Ala Lys Asp Leu Ile Asn Gln Thr Gly Asn Pro Thr Leu 5075 5080 5085 Asp Lys Ser Gln Val Glu Gln Leu Thr Gln Ala Val Thr Thr Ala Lys 5090 5095 5100 Asp Asn Leu His Gly Asp Gln Lys Leu Ala Arg Asp Gln Gln Gln Ala 5105 5110 5115 5120 Val Thr Thr Val Asn Ala Leu Pro Asn Leu Asn His Ala Gln Gln Gln 5125 5130 5135 Thr Leu Thr Asp Ala Ile Asn Ala Ala Pro Thr Arg Thr Glu Val Ala 5140 5145 5150 Gln His Val Gln Thr Ala Thr Glu Leu Asp His Ala Met Glu Thr Leu 5155 5160 5165 Lys Asn Lys Val Asp Gln Val Asn Thr Asp Lys Ala Gln Pro Asn Tyr 5170 5175 5180 Thr Glu Ala Ser Thr Asp Lys Lys Glu Ala Val Asp Gln Ala Leu Gln 5185 5190 5195 5200 Ala Ala Gln Ser Ile Thr Asp Pro Thr Asn Gly Ser Asn Ala Asn Lys 5205 5210 5215 Asp Ala Val Glu Gln Ala Leu Thr Lys Leu Gln Glu Lys Val Asn Glu 5220 5225 5230 Leu Asn Gly Asn Glu Arg Val Ala Glu Ala Lys Thr Gln Ala Lys Gln 5235 5240 5245 Thr Ile Asp Gln Leu Thr His Leu Asn Ala Asp Gln Ile Ala Thr Ala 5250 5255 5260 Lys Gln Asn Ile Asp Gln Ala Thr Lys Leu Gln Pro Ile Ala Glu Leu 5265 5270 5275 5280 Val Asp Gln Ala Thr Gln Leu Asn Gln Ser Met Asp Gln Leu Gln Gln 5285 5290 5295 Ala Val Asn Glu His Ala Asn Val Glu Gln Thr Ile Asp Tyr Thr Gln 5300 5305 5310 Ala Asp Ser Asp Lys Gln Lys Ala Tyr Lys Gln Ala Ile Ala Asp Ala 5315 5320 5325 Glu Asn Val Leu Lys Gln Asn Ala Asn Lys Gln Gln Val Asp Gln Ala 5330 5335 5340 Leu Gln Asn Ile Leu Asn Ala Lys Gln Ala Leu Asn Gly Asp Glu Arg 5345 5350 5355 5360 Val Ala Leu Ala Lys Thr Asn Gly Lys His Asp Ile Asp Gln Leu Asn 5365 5370 5375 Ala Leu Asn Asn Ala Gln Gln Asp Gly Phe Lys Gly Arg Ile Asp Gln 5380 5385 5390 Ser Asn Asp Leu Asn Gln Ile Gln Gln Ile Val Asp Glu Ala Lys Ala 5395 5400 5405 Leu Asn Arg Ala Met Asp Gln Leu Ser Gln Glu Ile Thr Gly Asn Glu 5410 5415 5420 Gly Arg Thr Lys Gly Ser Thr Asn Tyr Val Asn Ala Asp Thr Gln Val 5425 5430 5435 5440 Lys Gln Val Tyr Asp Glu Ala Val Asp Lys Ala Lys Gln Ala Leu Asp 5445 5450 5455 Lys Ser Ser Gly Gln Asn Leu Thr Ala Glu Gln Val Ile Lys Leu Asn 5460 5465 5470 Asp Ala Val Thr Ala Ala Lys Lys Ala Leu Asn Gly Glu Glu Arg Leu 5475 5480 5485 Asn Asn Arg Lys Ala Glu Ala Leu Gln Arg Leu Asp Gln Leu Thr His 5490 5495 5500 Leu Asn Asn Ala Gln Arg Gln Leu Ala Ile Gln Gln Ile Asn Asn Ala 5505 5510 5515 5520 Glu Thr Leu Asn Lys Ala Ser Arg Ala Ile Asn Arg Ala Thr Lys Leu 5525 5530 5535 Asp Asn Ala Met Gly Ala Val Gln Gln Tyr Ile Asp Glu Gln His Leu 5540 5545 5550 Gly Val Ile Ser Ser Thr Asn Tyr Ile Asn Ala Asp Asp Asn Leu Lys 5555 5560 5565 Ala Asn Tyr Asp Asn Ala Ile Ala Asn Ala Ala His Glu Leu Asp Lys 5570 5575 5580 Val Gln Gly Asn Ala Ile Ala Lys Ala Glu Ala Glu Gln Leu Lys Gln 5585 5590 5595 5600 Asn Ile Ile Asp Ala Gln Asn Ala Leu Asn Gly Asp Gln Asn Leu Ala 5605 5610 5615 Asn Ala Lys Asp Lys Ala Asn Ala Phe Val Asn Ser Leu Asn Gly Leu 5620 5625 5630 Asn Gln Gln Gln Gln Asp Leu Ala His Lys Ala Ile Asn Asn Ala Asp 5635 5640 5645 Thr Val Ser Asp Val Thr Asp Ile Val Asn Asn Gln Ile Asp Leu Asn 5650 5655 5660 Asp Ala Met Glu Thr Leu Lys His Leu Val Asp Asn Glu Ile Pro Asn 5665 5670 5675 5680 Ala Glu Gln Thr Val Asn Tyr Gln Asn Ala Asp Asp Asn Ala Lys Thr 5685 5690 5695 Asn Phe Asp Asp Ala Lys Arg Leu Ala Asn Thr Leu Leu Asn Ser Asp 5700 5705 5710 Asn Thr Asn Val Asn Asp Ile Asn Gly Ala Ile Gln Ala Val Asn Asp 5715 5720 5725 Ala Ile His Asn Leu Asn Gly Asp Gln Arg Leu Gln Asp Ala Lys Asp 5730 5735 5740 Lys Ala Ile Gln Ser Ile Asn Gln Ala Leu Ala Asn Lys Leu Lys Glu 5745 5750 5755 5760 Ile Glu Ala Ser Asn Ala Thr Asp Gln Asp Lys Leu Ile Ala Lys Asn 5765 5770 5775 Lys Ala Glu Glu Leu Ala Asn Ser Ile Ile Asn Asn Ile Asn Lys Ala 5780 5785 5790 Thr Ser Asn Gln Ala Val Ser Gln Val Gln Thr Ala Gly Asn His Ala 5795 5800 5805 Ile Glu Gln Val His Ala Asn Glu Ile Pro Lys Ala Lys Ile Asp Ala 5810 5815 5820 Asn Lys Asp Val Asp Lys Gln Val Gln Ala Leu Ile Asp Glu Ile Asp 5825 5830 5835 5840 Arg Asn Pro Asn Leu Thr Asp Lys Glu Lys Gln Ala Leu Lys Asp Arg 5845 5850 5855 Ile Asn Gln Ile Leu Gln Gln Gly His Asn Asp Ile Asn Asn Ala Leu 5860 5865 5870 Thr Lys Glu Glu Ile Glu Gln Ala Lys Ala Gln Leu Ala Gln Ala Leu 5875 5880 5885 Gln Asp Ile Lys Asp Leu Val Lys Ala Lys Glu Asp Ala Lys Gln Asp 5890 5895 5900 Val Asp Lys Gln Val Gln Ala Leu Ile Asp Glu Ile Asp Gln Asn Pro 5905 5910 5915 5920 Asn Leu Thr Asp Lys Glu Lys Gln Ala Leu Lys Asp Arg Ile Asn Gln 5925 5930 5935 Ile Leu Gln Gln Gly His Asn Gly Ile Asn Asn Ala Met Thr Lys Glu 5940 5945 5950 Glu Ile Glu Gln Ala Lys Ala Gln Leu Ala Gln Ala Leu Lys Glu Ile 5955 5960 5965 Lys Asp Leu Val Lys Ala Lys Glu Asn Ala Lys Gln Asp Val Asp Lys 5970 5975 5980 Gln Val Gln Ala Leu Ile Asp Glu Ile Asp Gln Asn Pro Asn Leu Thr 5985 5990 5995 6000 Asp Lys Glu Lys Gln Ala Leu Lys Asp Arg Ile Asn Gln Ile Leu Gln 6005 6010 6015 Gln Gly His Asn Asp Ile Asn Asn Ala Met Thr Lys Glu Glu Ile Glu 6020 6025 6030 Gln Ala Lys Ala Gln Leu Ala Gln Ala Leu Gln Asp Ile Lys Asp Leu 6035 6040 6045 Val Lys Ala Lys Glu Asp Ala Lys Asn Ala Ile Lys Ala Leu Ala Asn 6050 6055 6060 Ala Lys Arg Asp Gln Ile Asn Ser Asn Pro Asp Leu Thr Pro Glu Gln 6065 6070 6075 6080 Lys Ala Lys Ala Leu Lys Glu Ile Asp Glu Ala Glu Lys Arg Ala Leu 6085 6090 6095 Gln Asn Val Glu Asn Ala Gln Thr Ile Asp Gln Leu Asn Arg Gly Leu 6100 6105 6110 Asn Leu Gly Leu Asp Asp Ile Arg Asn Thr His Val Trp Glu Val Asp 6115 6120 6125 Glu Gln Pro Ala Val Asn Glu Ile Phe Glu Ala Thr Pro Glu Gln Ile 6130 6135 6140 Leu Val Asn Gly Glu Leu Ile Val His Arg Asp Asp Ile Ile Thr Glu 6145 6150 6155 6160 Gln Asp Ile Leu Ala His Ile Asn Leu Ile Asp Gln Leu Ser Ala Glu 6165 6170 6175 Val Ile Asp Thr Pro Ser Thr Ala Thr Ile Ser Asp Ser Leu Thr Ala 6180 6185 6190 Lys Val Glu Val Thr Leu Leu Asp Gly Ser Lys Val Ile Val Asn Val 6195 6200 6205 Pro Val Lys Val Val Glu Lys Glu Leu Ser Val Val Lys Gln Gln Ala 6210 6215 6220 Ile Glu Ser Ile Glu Asn Ala Ala Gln Gln Lys Ile Asp Glu Ile Asn 6225 6230 6235 6240 Asn Ser Val Thr Leu Thr Leu Glu Gln Lys Glu Ala Ala Ile Ala Glu 6245 6250 6255 Val Asn Lys Leu Lys Gln Gln Ala Ile Asp His Val Asn Asn Ala Pro 6260 6265 6270 Asp Val His Ser Val Glu Glu Ile Gln Gln Gln Glu Gln Ala Tyr Ile 6275 6280 6285 Glu Gln Phe Asn Pro Glu Gln Phe Thr Ile Glu Gln Ala Lys Ser Asn 6290 6295 6300 Ala Ile Lys Ser Ile Glu Asp Ala Ile Gln His Met Ile Asp Glu Ile 6305 6310 6315 6320 Lys Ala Arg Thr Asp Leu Thr Asp Lys Glu Lys Gln Glu Ala Ile Ala 6325 6330 6335 Lys Leu Asn Gln Leu Lys Glu Gln Ala Ile Gln Ala Ile Gln Arg Ala 6340 6345 6350 Gln Ser Ile Ser Glu Ile Thr Glu Gln Leu Glu Gln Phe Lys Ala Gln 6355 6360 6365 Met Lys Ala Ala Asn Pro Thr Ala Lys Glu Leu Ala Lys Arg Lys Gln 6370 6375 6380 Glu Ala Ile Ser Arg Ile Lys Asp Phe Ser Asn Glu Lys Ile Asn Ser 6385 6390 6395 6400 Ile Arg Asn Ser Glu Ile Gly Thr Ala Asp Glu Lys Gln Ala Ala Met 6405 6410 6415 Asn Gln Ile Asn Glu Ile Val Leu Glu Thr Ile Arg Asp Ile Asn Asn 6420 6425 6430 Ala His Thr Leu Gln Gln Val Glu Ala Ala Leu Asn Asn Gly Ile Ala 6435 6440 6445 Arg Ile Ser Ala Val Gln Ile Val Ile Ser Asp Arg Ala Lys Gln Ser 6450 6455 6460 Ser Ser Thr Gly Asn Glu Ser Asn Ser His Leu Thr Ile Gly Tyr Gly 6465 6470 6475 6480 Thr Ala Asn His Pro Phe Asn Ser Ser Thr Ile Gly His Lys Lys Lys 6485 6490 6495 Leu Asp Glu Asp Asp Asp Ile Asp Pro Leu His Met Arg His Phe Ser 6500 6505 6510 Asn Asn Phe Gly Asn Val Ile Lys Asn Ala Ile Gly Val Val Gly Ile 6515 6520 6525 Ser Gly Leu Leu Ala Ser Phe Trp Phe Phe Ile Ala Lys Arg Arg Arg 6530 6535 6540 Lys Glu Asp Glu Glu Glu Glu Leu Glu Ile Arg Asp Asn Asn Lys Asp 6545 6550 6555 6560 Ser Ile Lys Glu Thr Leu Asp Asp Thr Lys His Leu Pro Leu Leu Phe 6565 6570 6575 Ala Lys Arg Arg Arg Lys Glu Asp Glu Glu Asp Val Thr Val Glu Glu 6580 6585 6590 Lys Asp Ser Leu Asn Asn Gly Glu Ser Leu Asp Lys Val Lys His Thr 6595 6600 6605 Pro Phe Phe Leu Pro Lys Arg Arg Arg Lys Glu Asp Glu Glu Asp Val 6610 6615 6620 Glu Val Thr Asn Glu Asn Thr Asp Glu Lys Val Leu Lys Asp Asn Glu 6625 6630 6635 6640 His Ser Pro Leu Leu Phe Ala Lys Arg Arg Lys Asp Lys Glu Glu Asp 6645 6650 6655 Val Glu Thr Thr Thr Ser Ile Glu Ser Lys Asp Glu Asp Val Pro Leu 6660 6665 6670 Leu Leu Ala Lys Lys Lys Asn Gln Lys Asp Asn Gln Ser Lys Asp Lys 6675 6680 6685 Lys Ser Ala Ser Lys Asn Thr Ser Lys Lys Val Ala Ala Lys Lys Lys 6690 6695 6700 Lys Lys Lys Ser Lys Lys Asn Lys Lys 6705 6710 14 701 PRT S. epidermidis 14 Met Asn Asn Arg Asp Lys Leu Gln Lys Phe Ser Ile Arg Lys Tyr Ala 1 5 10 15 Ile Gly Thr Phe Ser Thr Val Ile Ala Thr Leu Val Phe Met Gly Ile 20 25 30 Asn Thr Asn His Ala Ser Ala Asp Glu Leu Asn Gln Asn Gln Lys Leu 35 40 45 Ile Lys Gln Leu Asn Gln Thr Asp Asp Asp Asp Ser Asn Thr His Ser 50 55 60 Gln Glu Ile Glu Asn Asn Lys Gln Asn Ser Ser Gly Gln Thr Glu Ser 65 70 75 80 Leu Arg Ser Ser Thr Ser Gln Asn Gln Ala Asn Ala Arg Leu Ser Asp 85 90 95 Gln Phe Lys Asp Thr Asn Glu Thr Ser Gln Gln Leu Pro Thr Asn Val 100 105 110

Ser Asp Asp Ser Ile Asn Gln Ser His Ser Glu Ala Asn Met Asn Asn 115 120 125 Glu Pro Leu Lys Val Asp Asn Ser Thr Met Gln Ala His Ser Lys Ile 130 135 140 Val Ser Asp Ser Asp Gly Asn Ala Ser Glu Asn Lys His His Lys Leu 145 150 155 160 Thr Glu Asn Val Leu Ala Glu Ser Arg Ala Ser Lys Asn Asp Lys Glu 165 170 175 Lys Glu Asn Leu Gln Glu Lys Asp Lys Ser Gln Gln Val His Pro Pro 180 185 190 Leu Asp Lys Asn Ala Leu Gln Ala Phe Phe Asp Ala Ser Tyr His Asn 195 200 205 Tyr Arg Met Ile Asp Arg Asp Arg Ala Asp Ala Thr Glu Tyr Gln Lys 210 215 220 Val Lys Ser Thr Phe Asp Tyr Val Asn Asp Leu Leu Gly Asn Asn Gln 225 230 235 240 Asn Ile Pro Ser Glu Gln Leu Val Ser Ala Tyr Gln Gln Leu Glu Lys 245 250 255 Ala Leu Glu Leu Ala Arg Thr Leu Pro Gln Gln Ser Thr Thr Glu Lys 260 265 270 Arg Gly Arg Arg Ser Thr Arg Ser Val Val Glu Asn Arg Ser Ser Arg 275 280 285 Ser Asp Tyr Leu Asp Ala Arg Thr Glu Tyr Tyr Val Ser Lys Asp Asp 290 295 300 Asp Asp Ser Gly Phe Pro Pro Gly Thr Phe Phe His Ala Ser Asn Arg 305 310 315 320 Arg Trp Pro Tyr Asn Leu Pro Arg Ser Arg Asn Ile Leu Arg Ala Ser 325 330 335 Asp Val Gln Gly Asn Ala Tyr Ile Thr Thr Lys Arg Leu Lys Asp Gly 340 345 350 Tyr Gln Trp Asp Ile Leu Phe Asn Ser Asn His Lys Gly His Glu Tyr 355 360 365 Met Tyr Tyr Trp Phe Gly Leu Pro Ser Asp Gln Thr Pro Thr Gly Pro 370 375 380 Val Thr Phe Thr Ile Ile Asn Arg Asp Gly Ser Ser Thr Ser Thr Gly 385 390 395 400 Gly Val Gly Phe Gly Ser Gly Ala Pro Leu Pro Gln Phe Trp Arg Ser 405 410 415 Ala Gly Ala Ile Asn Ser Ser Val Ala Asn Asp Phe Lys His Gly Ser 420 425 430 Ala Thr Asn Tyr Ala Phe Tyr Asp Gly Val Asn Asn Phe Ser Asp Phe 435 440 445 Ala Arg Gly Gly Glu Leu Tyr Phe Asp Arg Glu Gly Ala Thr Gln Thr 450 455 460 Asn Lys Tyr Tyr Gly Asp Glu Asn Phe Ala Leu Leu Asn Ser Glu Lys 465 470 475 480 Pro Asp Gln Ile Arg Gly Leu Asp Thr Ile Tyr Ser Phe Lys Gly Ser 485 490 495 Gly Asp Val Ser Tyr Arg Ile Ser Phe Lys Thr Gln Gly Ala Pro Thr 500 505 510 Ala Arg Leu Tyr Tyr Ala Ala Gly Ala Arg Ser Gly Glu Tyr Lys Gln 515 520 525 Ala Thr Asn Tyr Asn Gln Leu Tyr Val Glu Pro Tyr Lys Asn Tyr Arg 530 535 540 Asn Arg Val Gln Ser Asn Val Gln Val Lys Asn Arg Thr Leu His Leu 545 550 555 560 Lys Arg Thr Ile Arg Gln Phe Asp Pro Thr Leu Gln Arg Thr Thr Asp 565 570 575 Val Pro Ile Leu Asp Ser Asp Gly Ser Gly Ser Ile Asp Ser Val Tyr 580 585 590 Asp Pro Leu Ser Tyr Val Lys Asn Val Thr Gly Thr Val Leu Gly Ile 595 600 605 Tyr Pro Ser Tyr Leu Pro Tyr Asn Gln Glu Arg Trp Gln Gly Ala Asn 610 615 620 Ala Met Asn Ala Tyr Gln Ile Glu Glu Leu Phe Ser Gln Glu Asn Leu 625 630 635 640 Gln Asn Ala Ala Arg Ser Gly Arg Pro Ile Gln Phe Leu Val Gly Phe 645 650 655 Asp Val Glu Asp Ser His His Asn Pro Glu Thr Leu Leu Pro Val Asn 660 665 670 Leu Tyr Val Lys Pro Glu Leu Lys His Thr Ile Glu Leu Tyr His Asp 675 680 685 Asn Glu Lys Gln Asp Arg Lys Glu Phe Ser Val Ser Lys 690 695 700 15 9439 PRT S. epidermidis 15 Met Ser Gly Thr Leu His Asn Thr Val Gly Ser Gly Ile Leu Pro Tyr 1 5 10 15 Gln Gln Glu Ile Arg Ile Lys Leu Thr Ser Asn Glu Pro Ile Lys Asp 20 25 30 Ser Glu Trp Ser Ile Thr Gly Tyr Pro Asn Thr Leu Thr Leu Gln Asn 35 40 45 Ala Val Gly Arg Thr Asn Asn Ala Thr Glu Lys Asn Leu Ala Leu Val 50 55 60 Gly His Ile Asp Pro Gly Asn Tyr Phe Ile Thr Val Lys Phe Gly Asp 65 70 75 80 Lys Val Glu Gln Phe Glu Ile Arg Ser Lys Pro Thr Pro Pro Arg Ile 85 90 95 Ile Thr Thr Ala Asn Glu Leu Arg Gly Asn Pro Asn His Lys Pro Glu 100 105 110 Ile Arg Val Thr Asp Ile Pro Asn Asp Thr Thr Ala Lys Ile Lys Leu 115 120 125 Val Met Gly Gly Thr Asp Gly Asp His Asp Pro Glu Ile Asn Pro Tyr 130 135 140 Thr Val Pro Glu Asn Tyr Thr Val Val Ala Glu Ala Tyr His Asp Asn 145 150 155 160 Asp Pro Ser Lys Asn Gly Val Leu Thr Phe Arg Ser Ser Asp Tyr Leu 165 170 175 Lys Asp Leu Pro Leu Ser Gly Glu Leu Lys Ala Ile Val Tyr Tyr Asn 180 185 190 Gln Tyr Val Gln Ser Asn Phe Ser Lys Ser Val Pro Phe Ser Ser Asp 195 200 205 Thr Thr Pro Pro Thr Ile Asn Glu Pro Ala Gly Leu Val His Lys Tyr 210 215 220 Tyr Arg Gly Asp His Val Glu Ile Thr Leu Pro Val Thr Asp Asn Thr 225 230 235 240 Gly Gly Ser Gly Leu Arg Asp Val Asn Val Asn Leu Pro Gln Gly Trp 245 250 255 Thr Lys Thr Phe Thr Ile Asn Pro Asn Asn Asn Thr Glu Gly Thr Leu 260 265 270 Lys Leu Ile Gly Asn Ile Pro Ser Asn Glu Ala Tyr Asn Thr Thr Tyr 275 280 285 His Phe Asn Ile Thr Ala Thr Asp Asn Ser Gly Asn Thr Thr Asn Pro 290 295 300 Ala Lys Thr Phe Ile Leu Asn Val Gly Lys Leu Ala Asp Asp Leu Asn 305 310 315 320 Pro Val Gly Leu Ser Arg Asp Gln Leu Gln Leu Val Thr Asp Pro Ser 325 330 335 Ser Leu Ser Asn Ser Glu Arg Glu Glu Val Lys Arg Lys Ile Ser Glu 340 345 350 Ala Asn Ala Asn Ile Arg Ser Tyr Leu Leu Gln Asn Asn Pro Ile Leu 355 360 365 Ala Gly Val Asn Gly Asp Val Thr Phe Tyr Tyr Arg Asp Gly Ser Val 370 375 380 Asp Val Ile Asp Ala Glu Asn Val Ile Thr Tyr Glu Pro Glu Arg Lys 385 390 395 400 Ser Ile Phe Ser Glu Asn Gly Asn Thr Asn Lys Lys Glu Ala Val Ile 405 410 415 Thr Ile Ala Arg Gly Gln Asn Tyr Thr Ile Gly Pro Asn Leu Arg Lys 420 425 430 Tyr Phe Ser Leu Ser Asn Gly Ser Asp Leu Pro Asn Arg Asp Phe Thr 435 440 445 Ser Ile Ser Ala Ile Gly Ser Leu Pro Ser Ser Ser Glu Ile Ser Arg 450 455 460 Leu Asn Val Gly Asn Tyr Asn Tyr Arg Val Asn Ala Lys Asn Ala Tyr 465 470 475 480 His Lys Thr Gln Gln Glu Leu Asn Leu Lys Leu Lys Ile Val Glu Val 485 490 495 Asn Ala Pro Thr Gly Asn Asn Arg Val Tyr Arg Val Ser Thr Tyr Asn 500 505 510 Leu Thr Asn Asp Glu Ile Asn Lys Ile Lys Gln Ala Phe Lys Ala Ala 515 520 525 Asn Ser Gly Leu Asn Leu Asn Asp Asn Asp Ile Thr Val Ser Asn Asn 530 535 540 Phe Asp His Arg Asn Val Ser Ser Val Thr Val Thr Ile Arg Lys Gly 545 550 555 560 Asp Leu Ile Lys Glu Phe Ser Ser Asn Leu Asn Asn Met Asn Phe Leu 565 570 575 Arg Trp Val Asn Ile Arg Asp Asp Tyr Thr Ile Ser Trp Thr Ser Ser 580 585 590 Lys Ile Gln Gly Arg Asn Thr Asp Gly Gly Leu Glu Trp Ser Pro Asp 595 600 605 His Lys Ser Leu Ile Tyr Lys Tyr Asp Ala Thr Leu Gly Arg Gln Ile 610 615 620 Asn Thr Asn Asp Val Leu Thr Leu Leu Gln Ala Thr Ala Lys Asn Ser 625 630 635 640 Asn Leu Arg Ser Asn Ile Asn Ser Asn Glu Lys Gln Leu Ala Glu Arg 645 650 655 Gly Ser Asn Gly Tyr Ser Lys Ser Ile Ile Arg Asp Asp Gly Glu Lys 660 665 670 Ser Tyr Leu Leu Asn Ser Asn Pro Ile Gln Val Leu Asp Leu Val Glu 675 680 685 Pro Asp Asn Gly Tyr Gly Gly Arg Gln Val Ser His Ser Asn Val Ile 690 695 700 Tyr Asn Glu Lys Asn Ser Ser Ile Val Asn Gly Gln Val Pro Glu Ala 705 710 715 720 Asn Gly Ala Ser Ala Phe Asn Ile Asp Lys Val Val Lys Ala Asn Ala 725 730 735 Ala Asn Asn Gly Ile Met Gly Val Ile Tyr Lys Ala Gln Leu Tyr Leu 740 745 750 Ala Pro Tyr Ser Pro Lys Gly Tyr Ile Glu Lys Leu Gly Gln Asn Leu 755 760 765 Ser Asn Thr Asn Asn Val Ile Asn Val Tyr Phe Val Pro Ser Asp Lys 770 775 780 Val Asn Pro Ser Ile Thr Val Gly Asn Tyr Asp His His Thr Val Tyr 785 790 795 800 Ser Gly Glu Thr Phe Lys Asn Thr Ile Asn Val Asn Asp Asn Tyr Gly 805 810 815 Leu Asn Thr Val Ala Ser Thr Ser Asp Ser Ala Ile Thr Met Thr Arg 820 825 830 Asn Asn Asn Glu Leu Val Gly Gln Ala Pro Asn Val Thr Asn Ser Ile 835 840 845 Asn Lys Ile Val Lys Val Lys Ala Thr Asp Lys Ser Gly Asn Glu Ser 850 855 860 Ile Val Ser Phe Thr Val Asn Ile Lys Pro Leu Asn Glu Lys Tyr Arg 865 870 875 880 Ile Thr Thr Ser Ser Ser Asn Gln Thr Pro Val Arg Ile Ser Asn Ile 885 890 895 Gln Asn Asn Ala Asn Leu Ser Ile Glu Asp Gln Asn Arg Val Lys Ser 900 905 910 Ser Leu Ser Met Thr Lys Ile Leu Gly Thr Arg Asn Tyr Val Asn Glu 915 920 925 Ser Asn Asn Asp Val Arg Ser Gln Val Val Ser Lys Val Asn Arg Ser 930 935 940 Gly Asn Asn Ala Thr Val Asn Val Thr Thr Thr Phe Ser Asp Gly Thr 945 950 955 960 Thr Asn Thr Ile Thr Val Pro Val Lys His Val Leu Leu Glu Val Val 965 970 975 Pro Thr Thr Arg Thr Thr Val Arg Gly Gln Gln Phe Pro Thr Gly Lys 980 985 990 Gly Thr Ser Pro Asn Asp Phe Phe Ser Leu Arg Thr Gly Gly Pro Val 995 1000 1005 Asp Ala Arg Ile Val Trp Val Asn Asn Gln Gly Pro Asp Ile Asn Ser 1010 1015 1020 Asn Gln Ile Gly Arg Asp Leu Thr Leu His Ala Glu Ile Phe Phe Asp 1025 1030 1035 1040 Gly Glu Thr Thr Pro Ile Arg Lys Asp Thr Thr Tyr Lys Leu Ser Gln 1045 1050 1055 Ser Ile Pro Lys Gln Ile Tyr Glu Thr Thr Ile Asn Gly Arg Phe Asn 1060 1065 1070 Ser Ser Gly Asp Ala Tyr Pro Gly Asn Phe Val Gln Ala Val Asn Gln 1075 1080 1085 Tyr Trp Pro Glu His Met Asp Phe Arg Trp Ala Gln Gly Ser Gly Thr 1090 1095 1100 Pro Ser Ser Arg Asn Ala Gly Ser Phe Thr Lys Thr Val Thr Val Val 1105 1110 1115 1120 Tyr Gln Asn Gly Gln Thr Glu Asn Val Asn Val Leu Phe Lys Val Lys 1125 1130 1135 Pro Asn Lys Pro Val Ile Asp Ser Asn Ser Val Ile Ser Lys Gly Gln 1140 1145 1150 Leu Asn Gly Gln Gln Ile Leu Val Arg Asn Val Pro Gln Asn Ala Gln 1155 1160 1165 Val Thr Leu Tyr Gln Ser Asn Gly Thr Val Ile Pro Asn Thr Asn Thr 1170 1175 1180 Thr Ile Asp Ser Asn Gly Ile Ala Thr Val Thr Ile Gln Gly Thr Leu 1185 1190 1195 1200 Pro Thr Gly Asn Ile Thr Ala Lys Thr Ser Met Thr Asn Asn Val Thr 1205 1210 1215 Tyr Thr Lys Gln Asn Ser Ser Gly Ile Ala Ser Asn Thr Thr Glu Asp 1220 1225 1230 Ile Ser Val Phe Ser Glu Asn Ser Asp Gln Val Asn Val Thr Ala Gly 1235 1240 1245 Met Gln Ala Lys Asn Asp Gly Ile Lys Ile Ile Lys Gly Thr Asn Tyr 1250 1255 1260 Asn Phe Asn Asp Phe Asn Ser Phe Ile Ser Asn Ile Pro Ala His Ser 1265 1270 1275 1280 Thr Leu Thr Trp Asn Glu Glu Pro Asn Ser Trp Lys Asn Asn Ile Gly 1285 1290 1295 Thr Thr Thr Lys Thr Val Thr Val Thr Leu Pro Asn His Gln Gly Thr 1300 1305 1310 Arg Thr Val Asp Ile Pro Ile Thr Ile Tyr Pro Thr Val Thr Ala Lys 1315 1320 1325 Asn Pro Val Arg Asp Gln Lys Gly Arg Asn Leu Thr Asn Gly Thr Asp 1330 1335 1340 Val Tyr Asn Tyr Ile Ile Phe Glu Asn Asn Asn Arg Leu Gly Gly Thr 1345 1350 1355 1360 Ala Ser Trp Lys Asp Asn Arg Gln Pro Asp Lys Asn Ile Ala Gly Val 1365 1370 1375 Gln Asn Leu Ile Ala Leu Val Asn Tyr Pro Gly Ile Ser Thr Pro Leu 1380 1385 1390 Glu Val Pro Val Lys Val Trp Val Tyr Asn Phe Asp Phe Thr Gln Pro 1395 1400 1405 Ile Tyr Lys Ile Gln Val Gly Asp Thr Phe Pro Lys Gly Thr Trp Ala 1410 1415 1420 Gly Tyr Tyr Lys His Leu Glu Asn Gly Glu Gly Leu Pro Ile Asp Gly 1425 1430 1435 1440 Trp Lys Phe Tyr Trp Asn Gln Gln Ser Thr Gly Thr Thr Ser Asp Gln 1445 1450 1455 Trp Gln Ser Leu Ala Tyr Thr Arg Thr Pro Phe Val Lys Thr Gly Thr 1460 1465 1470 Tyr Asp Val Val Asn Pro Ser Asn Trp Gly Val Trp Gln Thr Ser Gln 1475 1480 1485 Ser Ala Lys Phe Ile Val Thr Asn Ala Lys Pro Asn Gln Pro Thr Ile 1490 1495 1500 Thr Gln Ser Lys Thr Gly Asp Val Thr Val Thr Pro Gly Ala Val Arg 1505 1510 1515 1520 Asn Ile Leu Ile Ser Gly Thr Asn Asp Tyr Ile Gln Ala Ser Ala Asp 1525 1530 1535 Lys Ile Val Ile Asn Lys Asn Gly Asn Lys Leu Thr Thr Phe Val Lys 1540 1545 1550 Asn Asn Asp Gly Arg Trp Thr Val Glu Thr Gly Ser Pro Asp Ile Asn 1555 1560 1565 Gly Ile Gly Pro Thr Asn Asn Gly Thr Ala Ile Ser Leu Ser Arg Leu 1570 1575 1580 Ala Val Arg Pro Gly Asp Ser Ile Glu Ala Ile Ala Thr Glu Gly Ser 1585 1590 1595 1600 Gly Glu Thr Ile Ser Thr Ser Ala Thr Ser Glu Ile Tyr Ile Val Lys 1605 1610 1615 Ala Pro Gln Pro Glu Gln Val Ala Thr His Thr Tyr Asp Asn Gly Thr 1620 1625 1630 Phe Asp Ile Leu Pro Asp Asn Ser Arg Asn Ser Leu Asn Pro Thr Glu 1635 1640 1645 Arg Val Glu Ile Asn Tyr Thr Glu Lys Leu Asn Gly Asn Glu Thr Gln 1650 1655 1660 Lys Ser Phe Thr Ile Thr Lys Asn Asn Asn Gly Lys Trp Thr Ile Asn 1665 1670 1675 1680 Asn Lys Pro Asn Tyr Val Glu Phe Asn Gln Asp Asn Gly Lys Val Val 1685 1690 1695 Phe Ser Ala Asn Thr Ile Lys Pro Asn Ser Gln Ile Thr Ile Thr Pro 1700 1705 1710 Lys Ala Gly Gln Gly Asn Thr Glu Asn Thr Asn Pro Thr Val Ile Gln 1715 1720 1725 Ala Pro Ala Gln His Thr Leu Thr Ile Asn Glu Ile Val Lys Glu Gln 1730 1735 1740 Gly Gln Asn Val Thr Asn Asp Asp Ile Asn Asn Ala Val Gln Val Pro 1745 1750 1755 1760 Asn Lys Asn Arg Val Ala Ile Lys Gln Gly Asn Ala Leu Pro Thr Asn 1765 1770 1775 Leu Ala Gly Gly Ser Thr Ser His Ile Pro Val Val Ile Tyr Tyr Ser 1780 1785 1790 Asp Gly Ser Ser Glu Glu Ala Thr Glu Thr Val Arg Thr Lys Val Asn 1795 1800 1805 Lys Thr Glu Leu Ile Asn Ala Arg Arg Arg Leu Asp Glu Glu Ile Ser 1810 1815 1820 Lys Glu Asn Lys Thr Pro Ser Ser Ile Arg Asn Phe Asp Gln Ala Met 1825 1830 1835 1840 Asn Arg Ala Gln Ser Gln

Ile Asn Thr Ala Lys Ser Asp Ala Asp Gln 1845 1850 1855 Val Ile Gly Thr Glu Phe Ala Thr Pro Gln Gln Val Asn Ser Ala Leu 1860 1865 1870 Ser Lys Val Gln Ala Ala Gln Asn Lys Ile Asn Glu Ala Lys Ala Leu 1875 1880 1885 Leu Gln Asn Lys Ala Asp Asn Ser Gln Leu Val Arg Ala Lys Glu Gln 1890 1895 1900 Leu Gln Gln Ser Ile Gln Pro Ala Ala Ser Thr Asp Gly Met Thr Gln 1905 1910 1915 1920 Asp Ser Thr Arg Asn Tyr Asn Asn Lys Arg Gln Ala Ala Glu Gln Ala 1925 1930 1935 Ile Gln His Ala Asn Ser Val Ile Asn Asn Gly Asp Ala Thr Ser Gln 1940 1945 1950 Gln Ile Asn Asp Ala Lys Asn Thr Val Glu Gln Ala Gln Arg Asp Tyr 1955 1960 1965 Val Glu Ala Lys Ser Asn Leu Arg Ala Asp Lys Ser Gln Leu Gln Ser 1970 1975 1980 Ala Tyr Asp Thr Leu Asn Arg Asp Val Leu Thr Asn Asp Lys Lys Pro 1985 1990 1995 2000 Ala Ser Val Arg Arg Tyr Asn Glu Ala Ile Ser Asn Ile Arg Lys Glu 2005 2010 2015 Leu Asp Thr Ala Lys Ala Asp Ala Ser Ser Thr Leu Arg Asn Thr Asn 2020 2025 2030 Pro Ser Val Glu Gln Val Arg Asp Ala Leu Asn Lys Ile Asn Thr Val 2035 2040 2045 Gln Pro Lys Val Asn Gln Ala Ile Ala Leu Leu Gln Pro Lys Glu Asn 2050 2055 2060 Asn Ser Glu Leu Val Gln Ala Lys Lys Arg Leu Gln Asp Ala Val Asn 2065 2070 2075 2080 Asp Ile Pro Gln Thr Gln Gly Met Thr Gln Gln Thr Ile Asn Asn Tyr 2085 2090 2095 Asn Asp Lys Gln Arg Glu Ala Glu Arg Ala Leu Thr Ser Ala Gln Arg 2100 2105 2110 Val Ile Asp Asn Gly Asp Ala Thr Thr Gln Glu Ile Thr Ser Glu Lys 2115 2120 2125 Ser Lys Val Glu Gln Ala Met Gln Ala Leu Thr Asn Ala Lys Ser Asn 2130 2135 2140 Leu Arg Ala Asp Lys Asn Glu Leu Gln Thr Ala Tyr Asn Lys Leu Ile 2145 2150 2155 2160 Glu Asn Val Ser Thr Asn Gly Lys Lys Pro Ala Ser Ile Arg Gln Tyr 2165 2170 2175 Glu Thr Ala Lys Ala Arg Ile Gln Asn Gln Ile Asn Asp Ala Lys Asn 2180 2185 2190 Glu Ala Glu Arg Ile Leu Gly Asn Asp Asn Pro Gln Val Ser Gln Val 2195 2200 2205 Thr Gln Ala Leu Asn Lys Ile Lys Ala Ile Gln Pro Lys Leu Thr Glu 2210 2215 2220 Ala Ile Asn Met Leu Gln Asn Lys Glu Asn Asn Thr Glu Leu Val Asn 2225 2230 2235 2240 Ala Lys Asn Arg Leu Glu Asn Ala Val Asn Asp Thr Asp Pro Thr His 2245 2250 2255 Gly Met Thr Gln Glu Thr Ile Asn Asn Tyr Asn Ala Lys Lys Arg Glu 2260 2265 2270 Ala Gln Asn Glu Ile Gln Lys Ala Asn Met Ile Ile Asn Asn Gly Asp 2275 2280 2285 Ala Thr Ala Gln Asp Ile Ser Ser Glu Lys Ser Lys Val Glu Gln Val 2290 2295 2300 Leu Gln Ala Leu Gln Asn Ala Lys Asn Asp Leu Arg Ala Asp Lys Arg 2305 2310 2315 2320 Glu Leu Gln Thr Ala Tyr Asn Lys Leu Ile Gln Asn Val Asn Thr Asn 2325 2330 2335 Gly Lys Lys Pro Ser Ser Ile Gln Asn Tyr Lys Ser Ala Arg Arg Asn 2340 2345 2350 Ile Glu Asn Gln Tyr Asn Thr Ala Lys Asn Glu Ala His Asn Val Leu 2355 2360 2365 Glu Asn Thr Asn Pro Thr Val Asn Ala Val Glu Asp Ala Leu Arg Lys 2370 2375 2380 Ile Asn Ala Ile Gln Pro Glu Val Thr Lys Ala Ile Asn Ile Leu Gln 2385 2390 2395 2400 Asp Lys Glu Asp Asn Ser Glu Leu Val Arg Ala Lys Glu Lys Leu Asp 2405 2410 2415 Gln Ala Ile Asn Ser Gln Pro Ser Leu Asn Gly Met Thr Gln Glu Ser 2420 2425 2430 Ile Asn Asn Tyr Thr Thr Lys Arg Arg Glu Ala Gln Asn Ile Ala Ser 2435 2440 2445 Ser Ala Asp Thr Ile Ile Asn Asn Gly Asp Ala Ser Ile Glu Gln Ile 2450 2455 2460 Thr Glu Asn Lys Ile Arg Val Glu Glu Ala Thr Asn Ala Leu Asn Glu 2465 2470 2475 2480 Ala Lys Gln His Leu Thr Ala Asp Thr Thr Ser Leu Lys Thr Glu Val 2485 2490 2495 Arg Lys Leu Ser Arg Arg Gly Asp Thr Asn Asn Lys Lys Pro Ser Ser 2500 2505 2510 Val Ser Ala Tyr Asn Asn Thr Ile His Ser Leu Gln Ser Glu Ile Thr 2515 2520 2525 Gln Thr Glu Asn Arg Ala Asn Thr Ile Ile Asn Lys Pro Ile Arg Ser 2530 2535 2540 Val Glu Glu Val Asn Asn Ala Leu His Glu Val Asn Gln Leu Asn Gln 2545 2550 2555 2560 Arg Leu Thr Asp Thr Ile Asn Leu Leu Gln Pro Leu Ala Asn Lys Glu 2565 2570 2575 Ser Leu Lys Glu Ala Arg Asn Arg Leu Glu Ser Lys Ile Asn Glu Thr 2580 2585 2590 Val Gln Thr Asp Gly Met Thr Gln Gln Ser Val Glu Asn Tyr Lys Gln 2595 2600 2605 Ala Lys Ile Lys Ala Gln Asn Glu Ser Ser Ile Ala Gln Thr Leu Ile 2610 2615 2620 Asn Asn Gly Asp Ala Ser Asp Gln Glu Val Ser Thr Glu Ile Glu Lys 2625 2630 2635 2640 Leu Asn Gln Lys Leu Ser Glu Leu Thr Asn Ser Ile Asn His Leu Thr 2645 2650 2655 Val Asn Lys Glu Pro Leu Glu Thr Ala Lys Asn Gln Leu Gln Ala Asn 2660 2665 2670 Ile Asp Gln Lys Pro Ser Thr Asp Gly Met Thr Gln Gln Ser Val Gln 2675 2680 2685 Ser Tyr Glu Arg Lys Leu Gln Glu Ala Lys Asp Lys Ile Asn Ser Ile 2690 2695 2700 Asn Asn Val Leu Ala Asn Asn Pro Asp Val Asn Ala Ile Arg Thr Asn 2705 2710 2715 2720 Lys Val Glu Thr Glu Gln Ile Asn Asn Glu Leu Thr Gln Ala Lys Gln 2725 2730 2735 Gly Leu Thr Val Asp Lys Gln Pro Leu Ile Asn Ala Lys Thr Ala Leu 2740 2745 2750 Gln Gln Ser Leu Asp Asn Gln Pro Ser Thr Thr Gly Met Thr Glu Ala 2755 2760 2765 Thr Ile Gln Asn Tyr Asn Ala Lys Arg Gln Lys Ala Glu Gln Val Ile 2770 2775 2780 Gln Asn Ala Asn Lys Ile Ile Glu Asn Ala Gln Pro Ser Val Gln Gln 2785 2790 2795 2800 Val Ser Asp Glu Lys Ser Lys Val Glu Gln Ala Leu Ser Glu Leu Asn 2805 2810 2815 Asn Ala Lys Ser Ala Leu Arg Ala Asp Lys Gln Glu Leu Gln Gln Ala 2820 2825 2830 Tyr Asn Gln Leu Ile Gln Pro Thr Asp Leu Asn Asn Lys Lys Pro Ala 2835 2840 2845 Ser Ile Thr Ala Tyr Asn Gln Arg Tyr Gln Gln Phe Ser Asn Glu Leu 2850 2855 2860 Asn Ser Thr Lys Thr Asn Thr Asp Arg Ile Leu Lys Glu Gln Asn Pro 2865 2870 2875 2880 Ser Val Ala Asp Val Asn Asn Ala Leu Asn Lys Val Arg Glu Val Gln 2885 2890 2895 Gln Lys Leu Asn Glu Ala Arg Ala Leu Leu Gln Asn Lys Glu Asp Asn 2900 2905 2910 Ser Ala Leu Val Arg Ala Lys Glu Gln Leu Gln Gln Ala Val Asp Gln 2915 2920 2925 Val Pro Ser Thr Glu Gly Met Thr Gln Gln Thr Lys Asp Asp Tyr Asn 2930 2935 2940 Ser Lys Gln Gln Ala Ala Gln Gln Glu Ile Ser Lys Ala Gln Gln Val 2945 2950 2955 2960 Ile Asp Asn Gly Asp Ala Thr Thr Gln Gln Ile Ser Asn Ala Lys Thr 2965 2970 2975 Asn Val Glu Arg Ala Leu Glu Ala Leu Asn Asn Ala Lys Thr Gly Leu 2980 2985 2990 Arg Ala Asp Lys Glu Glu Leu Gln Asn Ala Tyr Asn Gln Leu Thr Gln 2995 3000 3005 Asn Ile Asp Thr Ser Gly Lys Thr Pro Ala Ser Ile Arg Lys Tyr Asn 3010 3015 3020 Glu Ala Lys Ser Arg Ile Gln Thr Gln Ile Asp Ser Ala Lys Asn Glu 3025 3030 3035 3040 Ala Asn Ser Ile Leu Thr Asn Asp Asn Pro Gln Val Ser Gln Val Thr 3045 3050 3055 Ala Ala Leu Asn Lys Ile Lys Ala Val Gln Pro Glu Leu Asp Lys Ala 3060 3065 3070 Ile Ala Met Leu Lys Asn Lys Glu Asn Asn Asn Ala Leu Val Gln Ala 3075 3080 3085 Lys Gln Gln Leu Gln Gln Ile Val Asn Glu Val Asp Pro Thr Gln Gly 3090 3095 3100 Met Thr Thr Asp Thr Ala Asn Asn Tyr Lys Ser Lys Lys Arg Glu Ala 3105 3110 3115 3120 Glu Asp Glu Ile Gln Lys Ala Gln Gln Ile Ile Asn Asn Gly Asp Ala 3125 3130 3135 Thr Glu Gln Gln Ile Thr Asn Glu Thr Asn Arg Val Asn Gln Ala Ile 3140 3145 3150 Asn Ala Ile Asn Lys Ala Lys Asn Asp Leu Arg Ala Asp Lys Ser Gln 3155 3160 3165 Leu Glu Asn Ala Tyr Asn Gln Leu Ile Gln Asn Val Asp Thr Asn Gly 3170 3175 3180 Lys Lys Pro Ala Ser Ile Gln Gln Tyr Gln Ala Ala Arg Gln Ala Ile 3185 3190 3195 3200 Glu Thr Gln Tyr Asn Asn Ala Lys Ser Glu Ala His Gln Ile Leu Glu 3205 3210 3215 Asn Ser Asn Pro Ser Val Asn Glu Val Ala Gln Ala Leu Gln Lys Val 3220 3225 3230 Glu Ala Val Gln Leu Lys Val Asn Asp Ala Ile His Ile Leu Gln Asn 3235 3240 3245 Lys Glu Asn Asn Ser Ala Leu Val Thr Ala Lys Asn Gln Leu Gln Gln 3250 3255 3260 Ser Val Asn Asp Gln Pro Leu Thr Thr Gly Met Thr Gln Asp Ser Ile 3265 3270 3275 3280 Asn Asn Tyr Glu Ala Lys Arg Asn Glu Ala Gln Ser Ala Ile Arg Asn 3285 3290 3295 Ala Glu Ala Val Ile Asn Asn Gly Asp Ala Thr Ala Lys Gln Ile Ser 3300 3305 3310 Asp Glu Lys Ser Lys Val Glu Gln Ala Leu Ala His Leu Asn Asp Ala 3315 3320 3325 Lys Gln Gln Leu Thr Ala Asp Thr Thr Glu Leu Gln Thr Ala Val Gln 3330 3335 3340 Gln Leu Asn Arg Arg Gly Asp Thr Asn Asn Lys Lys Pro Arg Ser Ile 3345 3350 3355 3360 Asn Ala Tyr Asn Lys Ala Ile Gln Ser Leu Glu Thr Gln Ile Thr Ser 3365 3370 3375 Ala Lys Asp Asn Ala Asn Ala Val Ile Gln Lys Pro Ile Arg Thr Val 3380 3385 3390 Gln Glu Val Asn Asn Ala Leu Gln Gln Val Asn Gln Leu Asn Gln Gln 3395 3400 3405 Leu Thr Glu Ala Ile Asn Gln Leu Gln Pro Leu Ser Asn Asn Asp Ala 3410 3415 3420 Leu Lys Ala Ala Arg Leu Asn Leu Glu Asn Lys Ile Asn Gln Thr Val 3425 3430 3435 3440 Gln Thr Asp Gly Met Thr Gln Gln Ser Ile Glu Ala Tyr Gln Asn Ala 3445 3450 3455 Lys Arg Val Ala Gln Asn Glu Ser Asn Thr Ala Leu Ala Leu Ile Asn 3460 3465 3470 Asn Gly Asp Ala Asp Glu Gln Gln Ile Thr Thr Glu Thr Asp Arg Val 3475 3480 3485 Asn Gln Gln Thr Thr Asn Leu Thr Gln Ala Ile Asn Gly Leu Thr Val 3490 3495 3500 Asn Lys Glu Pro Leu Glu Thr Ala Lys Thr Ala Leu Gln Asn Asn Ile 3505 3510 3515 3520 Asp Gln Val Pro Ser Thr Asp Gly Met Thr Gln Gln Ser Val Ala Asn 3525 3530 3535 Tyr Asn Gln Lys Leu Gln Ile Ala Lys Asn Glu Ile Asn Thr Ile Asn 3540 3545 3550 Asn Val Leu Ala Asn Asn Pro Asp Val Asn Ala Ile Lys Thr Asn Lys 3555 3560 3565 Ala Glu Ala Glu Arg Ile Ser Asn Asp Leu Thr Gln Ala Lys Asn Asn 3570 3575 3580 Leu Gln Val Asp Thr Gln Pro Leu Glu Lys Ile Lys Arg Gln Leu Gln 3585 3590 3595 3600 Asp Glu Ile Asp Gln Gly Thr Asn Thr Asp Gly Met Thr Gln Asp Ser 3605 3610 3615 Val Asp Asn Tyr Asn Asp Ser Leu Ser Ala Ala Ile Ile Glu Lys Gly 3620 3625 3630 Lys Val Asn Lys Leu Leu Lys Arg Asn Pro Thr Val Glu Gln Val Lys 3635 3640 3645 Glu Ser Val Ala Asn Ala Gln Gln Val Ile Gln Asp Leu Gln Asn Ala 3650 3655 3660 Arg Thr Ser Leu Val Pro Asp Lys Thr Gln Leu Gln Glu Ala Lys Asn 3665 3670 3675 3680 Arg Leu Glu Asn Ser Ile Asn Gln Gln Thr Asp Thr Asp Gly Met Thr 3685 3690 3695 Gln Asp Ser Leu Asn Asn Tyr Asn Asp Lys Leu Ala Lys Ala Arg Gln 3700 3705 3710 Asn Leu Glu Lys Ile Ser Lys Val Leu Gly Gly Gln Pro Thr Val Ala 3715 3720 3725 Glu Ile Arg Gln Asn Thr Asp Glu Ala Asn Ala His Lys Gln Ala Leu 3730 3735 3740 Asp Thr Ala Arg Ser Gln Leu Thr Leu Asn Arg Glu Pro Tyr Ile Asn 3745 3750 3755 3760 His Ile Asn Asn Glu Ser His Leu Asn Asn Ala Gln Lys Asp Asn Phe 3765 3770 3775 Lys Ala Gln Val Asn Ser Ala Pro Asn His Asn Thr Leu Glu Thr Ile 3780 3785 3790 Lys Asn Lys Ala Asp Thr Leu Asn Gln Ser Met Thr Ala Leu Ser Glu 3795 3800 3805 Ser Ile Ala Asp Tyr Glu Asn Gln Lys Gln Gln Glu Asn Tyr Leu Asp 3810 3815 3820 Ala Ser Asn Asn Lys Arg Gln Asp Tyr Asp Asn Ala Val Asn Ala Ala 3825 3830 3835 3840 Lys Gly Ile Leu Asn Gln Thr Gln Ser Pro Thr Met Ser Ala Asp Val 3845 3850 3855 Ile Asp Gln Lys Ala Glu Asp Val Lys Arg Thr Lys Thr Ala Leu Asp 3860 3865 3870 Gly Asn Gln Arg Leu Glu Val Ala Lys Gln Gln Ala Leu Asn His Leu 3875 3880 3885 Asn Thr Leu Asn Asp Leu Asn Asp Ala Gln Arg Gln Thr Leu Thr Asp 3890 3895 3900 Thr Ile Asn His Ser Pro Asn Ile Asn Ser Val Asn Gln Ala Lys Glu 3905 3910 3915 3920 Lys Ala Asn Thr Val Asn Thr Ala Met Thr Gln Leu Lys Gln Thr Ile 3925 3930 3935 Ala Asn Tyr Asp Asp Glu Leu His Asp Gly Asn Tyr Ile Asn Ala Asp 3940 3945 3950 Lys Asp Lys Lys Asp Ala Tyr Asn Asn Ala Val Asn Asn Ala Lys Gln 3955 3960 3965 Leu Ile Asn Gln Ser Asp Ala Asn Gln Ala Gln Leu Asp Pro Ala Glu 3970 3975 3980 Ile Asn Lys Val Thr Gln Arg Val Asn Thr Thr Lys Asn Asp Leu Asn 3985 3990 3995 4000 Gly Asn Asp Lys Leu Ala Glu Ala Lys Arg Asp Ala Asn Thr Thr Ile 4005 4010 4015 Asp Gly Leu Thr Tyr Leu Asn Glu Ala Gln Arg Asn Lys Ala Lys Glu 4020 4025 4030 Asn Val Gly Lys Ala Ser Thr Lys Thr Asn Ile Thr Ser Gln Leu Gln 4035 4040 4045 Asp Tyr Asn Gln Leu Asn Ile Ala Met Gln Ala Leu Arg Asn Ser Val 4050 4055 4060 Asn Asp Val Asn Asn Val Lys Ala Asn Ser Asn Tyr Ile Asn Glu Asp 4065 4070 4075 4080 Asn Gly Pro Lys Glu Ala Tyr Asn Gln Ala Val Thr His Ala Gln Thr 4085 4090 4095 Leu Ile Asn Ala Gln Ser Asn Pro Glu Met Ser Arg Asp Val Val Asn 4100 4105 4110 Gln Lys Thr Gln Ala Val Asn Thr Ala His Gln Asn Leu His Gly Gln 4115 4120 4125 Gln Lys Leu Glu Gln Ala Gln Ser Ser Ala Asn Thr Glu Ile Gly Asn 4130 4135 4140 Leu Pro Asn Leu Thr Asn Thr Gln Lys Ala Lys Glu Lys Glu Leu Val 4145 4150 4155 4160 Asn Ser Lys Gln Thr Arg Thr Glu Val Gln Glu Gln Leu Asn Gln Ala 4165 4170 4175 Lys Ser Leu Asp Ser Ser Met Gly Thr Leu Lys Ser Leu Val Ala Lys 4180 4185 4190 Gln Pro Thr Val Gln Lys Thr Ser Val Tyr Ile Asn Glu Asp Gln Pro 4195 4200 4205 Glu Gln Ser Ala Tyr Asn Asp Ser Ile Thr Met Gly Gln Thr Ile Ile 4210 4215 4220 Asn Lys Thr Ala Asp Pro Val Leu Asp Lys Thr Leu Val Asp Asn Ala 4225 4230 4235 4240 Ile Ser Asn Ile Ser Thr Lys Glu Asn Ala Leu His Gly Glu Gln Lys 4245

4250 4255 Leu Thr Thr Ala Lys Thr Glu Ala Ile Asn Ala Leu Asn Thr Leu Ala 4260 4265 4270 Asp Leu Asn Thr Pro Gln Lys Glu Ala Ile Lys Thr Ala Ile Asn Thr 4275 4280 4285 Ala His Thr Arg Thr Asp Val Thr Ala Glu Gln Ser Lys Ala Asn Gln 4290 4295 4300 Ile Asn Ser Ala Met His Thr Leu Arg Gln Asn Ile Ser Asp Asn Glu 4305 4310 4315 4320 Ser Val Thr Asn Glu Ser Asn Tyr Ile Asn Ala Glu Pro Glu Lys Gln 4325 4330 4335 His Ala Phe Thr Glu Ala Leu Asn Asn Ala Lys Glu Ile Val Asn Glu 4340 4345 4350 Gln Gln Ala Thr Leu Asp Ala Asn Ser Ile Asn Gln Lys Ala Gln Ala 4355 4360 4365 Ile Leu Thr Thr Lys Asn Ala Leu Asp Gly Glu Glu Gln Leu Arg Arg 4370 4375 4380 Ala Lys Glu Asn Ala Asp Gln Glu Ile Asn Thr Leu Asn Gln Leu Thr 4385 4390 4395 4400 Asp Ala Gln Arg Asn Ser Glu Lys Gly Leu Val Asn Ser Ser Gln Thr 4405 4410 4415 Arg Thr Glu Val Ala Ser Gln Leu Ala Lys Ala Lys Glu Leu Asn Lys 4420 4425 4430 Val Met Glu Gln Leu Asn His Leu Ile Asn Gly Lys Asn Gln Met Ile 4435 4440 4445 Asn Ser Ser Lys Phe Ile Asn Glu Asp Ala Asn Gln Gln Gln Ala Tyr 4450 4455 4460 Ser Asn Ala Ile Ala Ser Ala Glu Ala Leu Lys Asn Lys Ser Gln Asn 4465 4470 4475 4480 Pro Glu Leu Asp Lys Val Thr Ile Glu Gln Ala Ile Asn Asn Ile Asn 4485 4490 4495 Ser Ala Ile Asn Asn Leu Asn Gly Glu Ala Lys Leu Thr Lys Ala Lys 4500 4505 4510 Glu Asp Ala Val Ala Ser Ile Asn Asn Leu Ser Gly Leu Thr Asn Glu 4515 4520 4525 Gln Lys Thr Lys Glu Asn Gln Ala Val Asn Gly Ala Gln Thr Arg Asp 4530 4535 4540 Gln Val Ala Asn Lys Leu Arg Asp Ala Glu Ala Leu Asp Gln Ser Met 4545 4550 4555 4560 Gln Thr Leu Arg Asp Leu Val Asn Asn Gln Asn Ala Ile His Ser Thr 4565 4570 4575 Ser Asn Tyr Phe Asn Glu Asp Ser Thr Gln Lys Asn Thr Tyr Asp Asn 4580 4585 4590 Ala Ile Asp Asn Gly Ser Thr Tyr Ile Thr Gly Gln His Asn Pro Glu 4595 4600 4605 Leu Asn Lys Ser Thr Ile Asp Gln Thr Ile Ser Arg Ile Asn Thr Ala 4610 4615 4620 Lys Asn Asp Leu His Gly Val Glu Lys Leu Gln Arg Asp Lys Gly Thr 4625 4630 4635 4640 Ala Asn Gln Glu Ile Gly Gln Leu Gly Tyr Leu Asn Asp Pro Gln Lys 4645 4650 4655 Ser Gly Glu Glu Ser Leu Val Asn Gly Ser Asn Thr Arg Ser Glu Val 4660 4665 4670 Glu Glu His Leu Asn Glu Ala Lys Ser Leu Asn Asn Ala Met Lys Gln 4675 4680 4685 Leu Arg Asp Lys Val Ala Glu Lys Thr Asn Val Lys Gln Ser Ser Asp 4690 4695 4700 Tyr Ile Asn Asp Ser Thr Glu His Gln Arg Gly Tyr Asp Gln Ala Leu 4705 4710 4715 4720 Gln Glu Ala Glu Asn Ile Ile Asn Glu Ile Gly Asn Pro Thr Leu Asn 4725 4730 4735 Lys Ser Glu Ile Glu Gln Lys Leu Gln Gln Leu Thr Asp Ala Gln Asn 4740 4745 4750 Ala Leu Gln Gly Ser His Leu Leu Glu Glu Ala Lys Asn Asn Ala Ile 4755 4760 4765 Thr Gly Ile Asn Lys Leu Thr Ala Leu Asn Asp Ala Gln Arg Gln Lys 4770 4775 4780 Ala Ile Glu Asn Val Gln Ala Gln Gln Thr Ile Pro Ala Val Asn Gln 4785 4790 4795 4800 Gln Leu Thr Leu Asp Arg Glu Ile Asn Thr Ala Met Gln Ala Leu Arg 4805 4810 4815 Asp Lys Val Gly Gln Gln Asn Asn Val His Gln Gln Ser Asn Tyr Phe 4820 4825 4830 Asn Glu Asp Glu Gln Pro Lys His Asn Tyr Asp Asn Ser Val Gln Ala 4835 4840 4845 Gly Gln Thr Ile Ile Asp Lys Leu Gln Asp Pro Ile Met Asn Lys Asn 4850 4855 4860 Glu Ile Glu Gln Ala Ile Asn Gln Ile Asn Thr Thr Gln Thr Ala Leu 4865 4870 4875 4880 Ser Gly Glu Asn Lys Leu His Thr Asp Gln Glu Ser Thr Asn Arg Gln 4885 4890 4895 Ile Glu Gly Leu Ser Ser Leu Asn Thr Ala Gln Ile Asn Ala Glu Lys 4900 4905 4910 Asp Leu Val Asn Gln Ala Lys Thr Arg Thr Asp Val Ala Gln Lys Leu 4915 4920 4925 Ala Ala Ala Lys Glu Ile Asn Ser Ala Met Ser Asn Leu Arg Asp Gly 4930 4935 4940 Ile Gln Asn Lys Glu Asp Ile Lys Arg Ser Ser Ala Tyr Ile Asn Ala 4945 4950 4955 4960 Asp Pro Thr Lys Val Thr Ala Tyr Asp Gln Ala Leu Gln Asn Ala Glu 4965 4970 4975 Asn Ile Ile Asn Ala Thr Pro Asn Val Glu Leu Asn Lys Ala Thr Ile 4980 4985 4990 Glu Gln Ala Leu Ser Arg Val Gln Gln Ala Gln Gln Asp Leu Asp Gly 4995 5000 5005 Val Gln Gln Leu Ala Asn Ala Lys Gln Gln Ala Thr Gln Thr Val Asn 5010 5015 5020 Gly Leu Asn Ser Leu Asn Asp Gly Gln Lys Arg Glu Leu Asn Leu Leu 5025 5030 5035 5040 Ile Asn Ser Ala Asn Thr Arg Thr Lys Val Gln Glu Glu Leu Asn Lys 5045 5050 5055 Ala Thr Glu Leu Asn His Ala Met Glu Ala Leu Arg Asn Ser Val Gln 5060 5065 5070 Asn Val Asp Gln Val Lys Gln Ser Ser Asn Tyr Val Asn Glu Asp Gln 5075 5080 5085 Pro Glu Gln His Asn Tyr Asp Asn Ala Val Asn Glu Ala Gln Ala Thr 5090 5095 5100 Ile Asn Asn Asn Ala Gln Pro Val Leu Asp Lys Leu Ala Ile Glu Arg 5105 5110 5115 5120 Leu Thr Gln Thr Val Asn Thr Thr Lys Asp Ala Leu His Gly Ala Gln 5125 5130 5135 Lys Leu Thr Gln Asp Gln Gln Ala Ala Glu Thr Gly Ile Arg Gly Leu 5140 5145 5150 Thr Ser Leu Asn Glu Pro Gln Lys Asn Ala Glu Val Ala Lys Val Thr 5155 5160 5165 Ala Ala Thr Thr Arg Asp Glu Val Arg Asn Ile Arg Gln Glu Ala Thr 5170 5175 5180 Thr Leu Asp Thr Ala Met Leu Gly Leu Arg Lys Ser Ile Lys Asp Lys 5185 5190 5195 5200 Asn Asp Thr Lys Asn Ser Ser Lys Tyr Ile Asn Glu Asp His Asp Gln 5205 5210 5215 Gln Gln Ala Tyr Asp Asn Ala Val Asn Asn Ala Gln Gln Val Ile Asp 5220 5225 5230 Glu Thr Gln Ala Thr Leu Ser Ser Asp Thr Ile Asn Gln Leu Ala Asn 5235 5240 5245 Ala Val Thr Gln Ala Lys Ser Asn Leu His Gly Asp Thr Lys Leu Gln 5250 5255 5260 His Asp Lys Asp Ser Ala Lys Gln Thr Ile Ala Gln Leu Gln Asn Leu 5265 5270 5275 5280 Asn Ser Ala Gln Lys His Met Glu Asp Ser Leu Ile Asp Asn Glu Ser 5285 5290 5295 Thr Arg Thr Gln Val Gln His Asp Leu Thr Glu Ala Gln Ala Leu Asp 5300 5305 5310 Gly Leu Met Gly Ala Leu Lys Glu Ser Ile Lys Asp Tyr Thr Asn Ile 5315 5320 5325 Val Ser Asn Gly Asn Tyr Ile Asn Ala Glu Pro Ser Lys Lys Gln Ala 5330 5335 5340 Tyr Asp Ala Ala Val Gln Asn Ala Gln Asn Ile Ile Asn Gly Thr Asn 5345 5350 5355 5360 Gln Pro Thr Ile Asn Lys Gly Asn Val Thr Thr Ala Thr Gln Thr Val 5365 5370 5375 Lys Asn Thr Lys Asp Ala Leu Asp Gly Asp His Arg Leu Glu Glu Ala 5380 5385 5390 Lys Asn Asn Ala Asn Gln Thr Ile Arg Asn Leu Ser Asn Leu Asn Asn 5395 5400 5405 Ala Gln Lys Asp Ala Glu Lys Asn Leu Val Asn Ser Ala Ser Thr Leu 5410 5415 5420 Glu Gln Val Gln Gln Asn Leu Gln Thr Ala Gln Gln Leu Asp Asn Ala 5425 5430 5435 5440 Met Gly Glu Leu Arg Gln Ser Ile Ala Lys Lys Asp Gln Val Lys Ala 5445 5450 5455 Asp Ser Lys Tyr Leu Asn Glu Asp Pro Gln Ile Lys Gln Asn Tyr Asp 5460 5465 5470 Asp Ala Val Gln Arg Val Glu Thr Ile Ile Asn Glu Thr Gln Asn Pro 5475 5480 5485 Glu Leu Leu Lys Ala Asn Ile Asp Gln Ala Thr Gln Ser Val Gln Asn 5490 5495 5500 Ala Glu Gln Ala Leu His Gly Ala Glu Lys Leu Asn Gln Asp Lys Gln 5505 5510 5515 5520 Thr Ser Ser Thr Glu Leu Asp Gly Leu Thr Asp Leu Thr Asp Ala Gln 5525 5530 5535 Arg Glu Lys Leu Arg Glu Gln Ile Asn Thr Ser Asn Ser Arg Asp Asp 5540 5545 5550 Ile Lys Gln Lys Ile Glu Gln Ala Lys Ala Leu Asn Asp Ala Met Lys 5555 5560 5565 Lys Leu Lys Glu Gln Val Ala Gln Lys Asp Gly Val His Ala Asn Ser 5570 5575 5580 Asp Tyr Thr Asn Glu Asp Ser Ala Gln Lys Asp Ala Tyr Asn Asn Ala 5585 5590 5595 5600 Leu Lys Gln Ala Glu Asp Ile Ile Asn Asn Ser Ser Asn Pro Asn Leu 5605 5610 5615 Asn Ala Gln Asp Ile Thr Asn Ala Leu Asn Asn Ile Lys Gln Ala Gln 5620 5625 5630 Asp Asn Leu His Gly Ala Gln Lys Leu Gln Gln Asp Lys Asn Thr Thr 5635 5640 5645 Asn Gln Ala Ile Gly Asn Leu Asn His Leu Asn Gln Pro Gln Lys Asp 5650 5655 5660 Ala Leu Ile Gln Ala Ile Asn Gly Ala Thr Ser Arg Asp Gln Val Ala 5665 5670 5675 5680 Glu Lys Leu Lys Glu Ala Glu Ala Leu Asp Glu Ala Met Lys Gln Leu 5685 5690 5695 Glu Asp Gln Val Asn Gln Asp Asp Gln Ile Ser Asn Ser Ser Pro Phe 5700 5705 5710 Ile Asn Glu Asp Ser Asp Lys Gln Lys Thr Tyr Asn Asp Lys Ile Gln 5715 5720 5725 Ala Ala Lys Glu Ile Ile Asn Gln Thr Ser Asn Pro Thr Leu Asp Lys 5730 5735 5740 Gln Lys Ile Ala Asp Thr Leu Gln Asn Ile Lys Asp Ala Val Asn Asn 5745 5750 5755 5760 Leu His Gly Asp Gln Lys Leu Ala Gln Ser Lys Gln Asp Ala Asn Asn 5765 5770 5775 Gln Leu Asn His Leu Asp Asp Leu Thr Glu Glu Gln Lys Asn His Phe 5780 5785 5790 Lys Pro Leu Ile Asn Asn Ala Asp Thr Arg Asp Glu Val Asn Lys Gln 5795 5800 5805 Leu Glu Ile Ala Lys Gln Leu Asn Gly Asp Met Ser Thr Leu His Lys 5810 5815 5820 Val Ile Asn Asp Lys Asp Gln Ile Gln His Leu Ser Asn Tyr Ile Asn 5825 5830 5835 5840 Ala Asp Asn Asp Lys Lys Gln Asn Tyr Asp Asn Ala Ile Lys Glu Ala 5845 5850 5855 Glu Asp Leu Ile His Asn His Pro Asp Thr Leu Asp His Lys Ala Leu 5860 5865 5870 Gln Asp Leu Leu Asn Lys Ile Asp Gln Ala His Asn Glu Leu Asn Gly 5875 5880 5885 Glu Ser Arg Phe Lys Gln Ala Leu Asp Asn Ala Leu Asn Asp Ile Asp 5890 5895 5900 Ser Leu Asn Ser Leu Asn Val Pro Gln Arg Gln Thr Val Lys Asp Asn 5905 5910 5915 5920 Ile Asn His Val Thr Thr Leu Glu Ser Leu Ala Gln Glu Leu Gln Lys 5925 5930 5935 Ala Lys Glu Leu Asn Asp Ala Met Lys Ala Met Arg Asp Ser Ile Met 5940 5945 5950 Asn Gln Glu Gln Ile Arg Lys Asn Ser Asn Tyr Thr Asn Glu Asp Leu 5955 5960 5965 Ala Gln Gln Asn Ala Tyr Asn His Ala Val Asp Lys Ile Asn Asn Ile 5970 5975 5980 Ile Gly Glu Asp Asn Ala Thr Met Asp Pro Gln Ile Ile Lys Gln Ala 5985 5990 5995 6000 Thr Gln Asp Ile Asn Thr Ala Ile Asn Gly Leu Asn Gly Asp Gln Lys 6005 6010 6015 Leu Gln Asp Ala Lys Thr Asp Ala Lys Gln Gln Ile Thr Asn Phe Thr 6020 6025 6030 Gly Leu Thr Glu Pro Gln Lys Gln Ala Leu Glu Asn Ile Ile Asn Gln 6035 6040 6045 Gln Thr Ser Arg Ala Asn Val Ala Lys Gln Leu Ser His Ala Lys Phe 6050 6055 6060 Leu Asn Gly Lys Met Glu Glu Leu Lys Val Ala Val Ala Lys Ala Ser 6065 6070 6075 6080 Leu Val Arg Gln Asn Ser Asn Tyr Ile Asn Glu Asp Val Ser Glu Lys 6085 6090 6095 Glu Ala Tyr Glu Gln Ala Ile Ala Lys Gly Gln Glu Ile Ile Asn Ser 6100 6105 6110 Glu Asn Asn Pro Thr Ile Ser Ser Thr Asp Ile Asn Arg Thr Ile Gln 6115 6120 6125 Glu Ile Asn Asp Ala Glu Gln Asn Leu His Gly Asp Asn Lys Leu Arg 6130 6135 6140 Gln Ala Gln Glu Ile Ala Lys Asn Glu Ile Gln Asn Leu Asp Gly Leu 6145 6150 6155 6160 Asn Ser Ala Gln Ile Thr Lys Leu Ile Gln Asp Ile Gly Arg Thr Thr 6165 6170 6175 Thr Lys Pro Ala Val Thr Gln Lys Leu Glu Glu Ala Lys Ala Ile Asn 6180 6185 6190 Gln Ala Met Gln Gln Leu Lys Gln Ser Ile Ala Asp Lys Asp Ala Thr 6195 6200 6205 Leu Asn Ser Ser Asn Tyr Leu Asn Glu Asp Ser Glu Lys Lys Leu Ala 6210 6215 6220 Tyr Asp Asn Ala Val Ser Gln Ala Glu Gln Leu Ile Asn Gln Leu Asn 6225 6230 6235 6240 Asp Pro Thr Met Asp Ile Ser Asn Ile Gln Ala Ile Thr Gln Lys Val 6245 6250 6255 Ile Gln Ala Lys Asp Ser Leu His Gly Ala Asn Lys Leu Ala Gln Asn 6260 6265 6270 Gln Ala Asp Ser Asn Leu Ile Ile Asn Gln Ser Thr Asn Leu Asn Asp 6275 6280 6285 Lys Gln Lys Gln Ala Leu Asn Asp Leu Ile Asn His Ala Gln Thr Lys 6290 6295 6300 Gln Gln Val Ala Glu Ile Ile Ala Gln Ala Asn Lys Leu Asn Asn Glu 6305 6310 6315 6320 Met Gly Thr Leu Lys Thr Leu Val Glu Glu Gln Ser Asn Val His Gln 6325 6330 6335 Gln Ser Lys Tyr Ile Asn Glu Asp Pro Gln Val Gln Asn Ile Tyr Asn 6340 6345 6350 Asp Ser Ile Gln Lys Gly Arg Glu Ile Leu Asn Gly Thr Thr Asp Asp 6355 6360 6365 Val Leu Asn Asn Asn Lys Ile Ala Asp Ala Ile Gln Asn Ile His Leu 6370 6375 6380 Thr Lys Asn Asp Leu His Gly Asp Gln Lys Leu Gln Lys Ala Gln Gln 6385 6390 6395 6400 Asp Ala Thr Asn Glu Leu Asn Tyr Leu Thr Asn Leu Asn Asn Ser Gln 6405 6410 6415 Arg Gln Ser Glu His Asp Glu Ile Asn Ser Ala Pro Ser Arg Thr Glu 6420 6425 6430 Val Ser Asn Asp Leu Asn His Ala Lys Ala Leu Asn Glu Ala Met Arg 6435 6440 6445 Gln Leu Glu Asn Glu Val Ala Leu Glu Asn Ser Val Lys Lys Leu Ser 6450 6455 6460 Asp Phe Ile Asn Glu Asp Glu Ala Ala Gln Asn Glu Tyr Ser Asn Ala 6465 6470 6475 6480 Leu Gln Lys Ala Lys Asp Ile Ile Asn Gly Val Pro Ser Ser Thr Leu 6485 6490 6495 Asp Lys Ala Thr Ile Glu Asp Ala Leu Leu Glu Leu Gln Asn Ala Arg 6500 6505 6510 Glu Ser Leu His Gly Glu Gln Lys Leu Gln Glu Ala Lys Asn Gln Ala 6515 6520 6525 Val Ala Glu Ile Asp Asn Leu Gln Ala Leu Asn Pro Gly Gln Val Leu 6530 6535 6540 Ala Glu Lys Thr Leu Val Asn Gln Ala Ser Thr Lys Pro Glu Val Gln 6545 6550 6555 6560 Glu Ala Leu Gln Lys Ala Lys Glu Leu Asn Glu Ala Met Lys Ala Leu 6565 6570 6575 Lys Thr Glu Ile Asn Lys Lys Glu Gln Ile Lys Ala Asp Ser Arg Tyr 6580 6585 6590 Val Asn Ala Asp Ser Gly Leu Gln Ala Asn Tyr Asn Ser Ala Leu Asn 6595 6600 6605 Tyr Gly Ser Gln Ile Ile Ala Thr Thr Gln Pro Pro Glu Leu Asn Lys 6610 6615 6620 Asp Val Ile Asn Arg Ala Thr Gln Thr Ile Lys Thr Ala Glu Asn Asn 6625 6630 6635 6640 Leu Asn Gly Gln Ser Lys Leu Ala Glu Ala Lys Ser Asp Gly Asn Gln 6645 6650 6655 Ser Ile Glu His Leu Gln Gly Leu Thr Gln Ser

Gln Lys Asp Lys Gln 6660 6665 6670 His Asp Leu Ile Asn Gln Ala Gln Thr Lys Gln Gln Val Asp Asp Ile 6675 6680 6685 Val Asn Asn Ser Lys Gln Leu Asp Asn Ser Met Asn Gln Leu Gln Gln 6690 6695 6700 Ile Val Asn Asn Asp Asn Thr Val Lys Gln Asn Ser Asp Phe Ile Asn 6705 6710 6715 6720 Glu Asp Ser Ser Gln Gln Asp Ala Tyr Asn His Ala Ile Gln Ala Ala 6725 6730 6735 Lys Asp Leu Ile Thr Ala His Pro Thr Ile Met Asp Lys Asn Gln Ile 6740 6745 6750 Asp Gln Ala Ile Glu Asn Ile Lys Gln Ala Leu Asn Asp Leu His Gly 6755 6760 6765 Ser Asn Lys Leu Ser Glu Asp Lys Lys Glu Ala Ser Glu Gln Leu Gln 6770 6775 6780 Asn Leu Asn Ser Leu Thr Asn Gly Gln Lys Asp Thr Ile Leu Asn His 6785 6790 6795 6800 Ile Phe Ser Ala Pro Thr Arg Ser Gln Val Gly Glu Lys Ile Ala Ser 6805 6810 6815 Ala Lys Gln Leu Asn Asn Thr Met Lys Ala Leu Arg Asp Ser Ile Ala 6820 6825 6830 Asp Asn Asn Glu Ile Leu Gln Ser Ser Lys Tyr Phe Asn Glu Asp Ser 6835 6840 6845 Glu Gln Gln Asn Ala Tyr Asn Gln Ala Val Asn Lys Ala Lys Asn Ile 6850 6855 6860 Ile Asn Asp Gln Pro Thr Pro Val Met Ala Asn Asp Glu Ile Gln Ser 6865 6870 6875 6880 Val Leu Asn Glu Val Lys Gln Thr Lys Asp Asn Leu His Gly Asp Gln 6885 6890 6895 Lys Leu Ala Asn Asp Lys Thr Asp Ala Gln Ala Thr Leu Asn Ala Leu 6900 6905 6910 Asn Tyr Leu Asn Gln Ala Gln Arg Gly Asn Leu Glu Thr Lys Val Gln 6915 6920 6925 Asn Ser Asn Ser Arg Pro Glu Val Gln Lys Val Val Gln Leu Ala Asn 6930 6935 6940 Gln Leu Asn Asp Ala Met Lys Lys Leu Asp Asp Ala Leu Thr Gly Asn 6945 6950 6955 6960 Asp Ala Ile Lys Gln Thr Ser Asn Tyr Ile Asn Glu Asp Thr Ser Gln 6965 6970 6975 Gln Val Asn Phe Asp Glu Tyr Thr Asp Arg Gly Lys Asn Ile Val Ala 6980 6985 6990 Glu Gln Thr Asn Pro Asn Met Ser Pro Thr Asn Ile Asn Thr Ile Ala 6995 7000 7005 Asp Lys Ile Thr Glu Ala Lys Asn Asp Leu His Gly Val Gln Lys Leu 7010 7015 7020 Lys Gln Ala Gln Gln Gln Ser Ile Asn Thr Ile Asn Gln Met Thr Gly 7025 7030 7035 7040 Leu Asn Gln Ala Gln Lys Glu Gln Leu Asn Gln Glu Ile Gln Gln Thr 7045 7050 7055 Gln Thr Arg Ser Glu Val His Gln Val Ile Asn Lys Ala Gln Ala Leu 7060 7065 7070 Asn Asp Ser Met Asn Thr Leu Arg Gln Ser Ile Thr Asp Glu His Glu 7075 7080 7085 Val Lys Gln Thr Ser Asn Tyr Ile Asn Glu Thr Val Gly Asn Gln Thr 7090 7095 7100 Ala Tyr Asn Asn Ala Val Asp Arg Val Lys Gln Ile Ile Asn Gln Thr 7105 7110 7115 7120 Ser Asn Pro Thr Met Asn Pro Leu Glu Val Glu Arg Ala Thr Ser Asn 7125 7130 7135 Val Lys Ile Ser Lys Asp Ala Leu His Gly Glu Arg Glu Leu Asn Asp 7140 7145 7150 Asn Lys Asn Ser Lys Thr Phe Ala Val Asn His Leu Asp Asn Leu Asn 7155 7160 7165 Gln Ala Gln Lys Glu Ala Leu Thr His Glu Ile Glu Gln Ala Thr Ile 7170 7175 7180 Val Ser Gln Val Asn Asn Ile Tyr Asn Lys Ala Lys Ala Leu Asn Asn 7185 7190 7195 7200 Asp Met Lys Lys Leu Lys Asp Ile Val Ala Gln Gln Asp Asn Val Arg 7205 7210 7215 Gln Ser Asn Asn Tyr Ile Asn Glu Asp Ser Thr Pro Gln Asn Met Tyr 7220 7225 7230 Asn Asp Thr Ile Asn His Ala Gln Ser Ile Ile Asp Gln Val Ala Asn 7235 7240 7245 Pro Thr Met Ser His Asp Glu Ile Glu Asn Ala Ile Asn Asn Ile Lys 7250 7255 7260 His Ala Ile Asn Ala Leu Asp Gly Glu His Lys Leu Gln Gln Ala Lys 7265 7270 7275 7280 Glu Asn Ala Asn Leu Leu Ile Asn Ser Leu Asn Asp Leu Asn Ala Pro 7285 7290 7295 Gln Arg Asp Ala Ile Asn Arg Leu Val Asn Glu Ala Gln Thr Arg Glu 7300 7305 7310 Lys Val Ala Glu Gln Leu Gln Ser Ala Gln Ala Leu Asn Asp Ala Met 7315 7320 7325 Lys His Leu Arg Asn Ser Ile Gln Asn Gln Ser Ser Val Arg Gln Glu 7330 7335 7340 Ser Lys Tyr Ile Asn Ala Ser Asp Ala Lys Lys Glu Gln Tyr Asn His 7345 7350 7355 7360 Ala Val Arg Glu Val Glu Asn Ile Ile Asn Glu Gln His Pro Thr Leu 7365 7370 7375 Asp Lys Glu Ile Ile Lys Gln Leu Thr Asp Gly Val Asn Gln Ala Asn 7380 7385 7390 Asn Asp Leu Asn Gly Val Glu Leu Leu Asp Ala Asp Lys Gln Asn Ala 7395 7400 7405 His Gln Ser Ile Pro Thr Leu Met His Leu Asn Gln Ala Gln Gln Asn 7410 7415 7420 Ala Leu Asn Glu Lys Ile Asn Asn Ala Val Thr Arg Thr Glu Val Ala 7425 7430 7435 7440 Ala Ile Ile Gly Gln Ala Lys Leu Leu Asp His Ala Met Glu Asn Leu 7445 7450 7455 Glu Glu Ser Ile Lys Asp Lys Glu Gln Val Lys Gln Ser Ser Asn Tyr 7460 7465 7470 Ile Asn Glu Asp Ser Asp Val Gln Glu Thr Tyr Asp Asn Ala Val Asp 7475 7480 7485 His Val Thr Glu Ile Leu Asn Gln Thr Val Asn Pro Thr Leu Ser Ile 7490 7495 7500 Glu Asp Ile Glu His Ala Ile Asn Glu Val Asn Gln Ala Lys Lys Gln 7505 7510 7515 7520 Leu Arg Gly Lys Gln Lys Leu Tyr Gln Thr Ile Asp Leu Ala Asp Lys 7525 7530 7535 Glu Leu Ser Lys Leu Asp Asp Leu Thr Ser Gln Gln Ser Ser Ser Ile 7540 7545 7550 Ser Asn Gln Ile Tyr Thr Ala Lys Thr Arg Thr Glu Val Ala Gln Ala 7555 7560 7565 Ile Glu Lys Ala Lys Ser Leu Asn His Ala Met Lys Ala Leu Asn Lys 7570 7575 7580 Val Tyr Lys Asn Ala Asp Lys Val Leu Asp Ser Ser Arg Phe Ile Asn 7585 7590 7595 7600 Glu Asp Gln Pro Glu Lys Lys Ala Tyr Gln Gln Ala Ile Asn His Val 7605 7610 7615 Asp Ser Ile Ile His Arg Gln Thr Asn Pro Glu Met Asp Pro Thr Val 7620 7625 7630 Ile Asn Ser Ile Thr His Glu Leu Glu Thr Ala Gln Asn Asn Leu His 7635 7640 7645 Gly Asp Gln Lys Leu Ala His Ala Gln Gln Asp Ala Ala Asn Val Ile 7650 7655 7660 Asn Gly Leu Ile His Leu Asn Val Ala Gln Arg Glu Val Met Ile Asn 7665 7670 7675 7680 Thr Asn Thr Asn Ala Thr Thr Arg Glu Lys Val Ala Lys Asn Leu Asp 7685 7690 7695 Asn Ala Gln Ala Leu Asp Lys Ala Met Glu Thr Leu Gln Gln Val Val 7700 7705 7710 Ala His Lys Asn Asn Ile Leu Asn Asp Ser Lys Tyr Leu Asn Glu Asp 7715 7720 7725 Ser Lys Tyr Gln Gln Gln Tyr Asp Arg Val Ile Ala Asp Ala Glu Gln 7730 7735 7740 Leu Leu Asn Gln Thr Thr Asn Pro Thr Leu Glu Pro Tyr Lys Val Asp 7745 7750 7755 7760 Ile Val Lys Asp Asn Val Leu Ala Asn Glu Lys Ile Leu Phe Gly Ala 7765 7770 7775 Glu Lys Leu Ser Tyr Asp Lys Ser Asn Ala Asn Asp Glu Ile Lys His 7780 7785 7790 Met Asn Tyr Leu Asn Asn Ala Gln Lys Gln Ser Ile Lys Asp Met Ile 7795 7800 7805 Ser His Ala Ala Leu Arg Thr Glu Val Lys Gln Leu Leu Gln Gln Ala 7810 7815 7820 Lys Ile Leu Asp Glu Ala Met Lys Ser Leu Glu Asp Lys Thr Gln Val 7825 7830 7835 7840 Val Ile Thr Asp Thr Thr Leu Pro Asn Tyr Thr Glu Ala Ser Glu Asp 7845 7850 7855 Lys Lys Glu Lys Val Asp Gln Thr Val Ser His Ala Gln Ala Ile Ile 7860 7865 7870 Asp Lys Ile Asn Gly Ser Asn Val Ser Leu Asp Gln Val Arg Gln Ala 7875 7880 7885 Leu Glu Gln Leu Thr Gln Ala Ser Glu Asn Leu Asp Gly Asp Gln Arg 7890 7895 7900 Val Glu Glu Ala Lys Val His Ala Asn Gln Thr Ile Asp Gln Leu Thr 7905 7910 7915 7920 His Leu Asn Ser Leu Gln Gln Gln Thr Ala Lys Glu Ser Val Lys Asn 7925 7930 7935 Ala Thr Lys Leu Glu Glu Ile Ala Thr Val Ser Asn Asn Ala Gln Ala 7940 7945 7950 Leu Asn Lys Val Met Gly Lys Leu Glu Gln Phe Ile Asn His Ala Asp 7955 7960 7965 Ser Val Glu Asn Ser Asp Asn Tyr Arg Gln Ala Asp Asp Asp Lys Ile 7970 7975 7980 Ile Ala Tyr Asp Glu Ala Leu Glu His Gly Gln Asp Ile Gln Lys Thr 7985 7990 7995 8000 Asn Ala Thr Gln Asn Glu Thr Lys Gln Ala Leu Gln Gln Leu Ile Tyr 8005 8010 8015 Ala Glu Thr Ser Leu Asn Gly Phe Glu Arg Leu Asn His Ala Arg Pro 8020 8025 8030 Arg Ala Leu Glu Tyr Ile Lys Ser Leu Glu Lys Ile Asn Asn Ala Gln 8035 8040 8045 Lys Ser Ala Leu Glu Asp Lys Val Thr Gln Ser His Asp Leu Leu Glu 8050 8055 8060 Leu Glu His Ile Val Asn Glu Gly Thr Asn Leu Asn Asp Ile Met Gly 8065 8070 8075 8080 Glu Leu Ala Asn Ala Ile Val Asn Asn Tyr Ala Pro Thr Lys Ala Ser 8085 8090 8095 Ile Asn Tyr Ile Asn Ala Asp Asn Leu Arg Lys Asp Asn Phe Thr Gln 8100 8105 8110 Ala Ile Asn Asn Ala Arg Asp Ala Leu Asn Lys Thr Gln Gly Gln Asn 8115 8120 8125 Leu Asp Phe Asn Ala Ile Asp Thr Phe Lys Asp Asp Ile Phe Lys Thr 8130 8135 8140 Lys Asp Ala Leu Asn Gly Ile Glu Arg Leu Thr Ala Ala Lys Ser Lys 8145 8150 8155 8160 Ala Glu Lys Leu Ile Asp Ser Leu Lys Phe Ile Asn Lys Ala Gln Phe 8165 8170 8175 Thr His Ala Asn Asp Glu Ile Met Asn Thr Asn Ser Ile Ala Gln Leu 8180 8185 8190 Ser Arg Ile Val Asn Gln Ala Phe Asp Leu Asn Asp Ala Met Lys Ser 8195 8200 8205 Leu Arg Asp Glu Leu Asn Asn Gln Ala Phe Pro Val Gln Ala Ser Ser 8210 8215 8220 Asn Tyr Ile Asn Ser Asp Glu Asp Leu Lys Gln Gln Phe Asp His Ala 8225 8230 8235 8240 Leu Ser Asn Ala Arg Lys Val Leu Ala Lys Glu Asn Gly Lys Asn Leu 8245 8250 8255 Asp Glu Lys Gln Ile Gln Gly Leu Lys Gln Val Ile Glu Asp Thr Lys 8260 8265 8270 Asp Ala Leu Asn Gly Ile Gln Arg Leu Ser Lys Ala Lys Ala Lys Ala 8275 8280 8285 Ile Gln Tyr Val Gln Ser Leu Ser Tyr Ile Asn Asp Ala Gln Arg His 8290 8295 8300 Ile Ala Glu Asn Asn Ile His Asn Ser Asp Asp Leu Ser Ser Leu Ala 8305 8310 8315 8320 Asn Thr Leu Ser Lys Ala Ser Asp Leu Asp Asn Ala Met Lys Asp Leu 8325 8330 8335 Arg Asp Thr Ile Glu Ser Asn Ser Thr Ser Val Pro Asn Ser Val Asn 8340 8345 8350 Tyr Ile Asn Ala Asp Lys Asn Leu Gln Ile Glu Phe Asp Glu Ala Leu 8355 8360 8365 Gln Gln Ala Ser Ala Thr Ser Ser Lys Thr Ser Glu Asn Pro Ala Thr 8370 8375 8380 Ile Glu Glu Val Leu Gly Leu Ser Gln Ala Ile Tyr Asp Thr Lys Asn 8385 8390 8395 8400 Ala Leu Asn Gly Glu Gln Arg Leu Ala Thr Glu Lys Ser Lys Asp Leu 8405 8410 8415 Lys Leu Ile Lys Gly Leu Lys Asp Leu Asn Lys Ala Gln Leu Glu Asp 8420 8425 8430 Val Thr Asn Lys Val Asn Ser Ala Asn Thr Leu Thr Glu Leu Ser Gln 8435 8440 8445 Leu Thr Gln Ser Thr Leu Glu Leu Asn Asp Lys Met Lys Leu Leu Arg 8450 8455 8460 Asp Lys Leu Lys Thr Leu Val Asn Pro Val Lys Ala Ser Leu Asn Tyr 8465 8470 8475 8480 Arg Asn Ala Asp Tyr Asn Leu Lys Arg Gln Phe Asn Lys Ala Leu Lys 8485 8490 8495 Glu Ala Lys Gly Val Leu Asn Lys Asn Ser Gly Thr Asn Val Asn Ile 8500 8505 8510 Asn Asp Ile Gln His Leu Leu Thr Gln Ile Asp Asn Ala Lys Asp Gln 8515 8520 8525 Leu Asn Gly Glu Arg Arg Leu Lys Glu His Gln Gln Lys Ser Glu Val 8530 8535 8540 Phe Ile Ile Lys Glu Leu Asp Ile Leu Asn Asn Ala Gln Lys Ala Ala 8545 8550 8555 8560 Ile Ile Asn Gln Ile Arg Ala Ser Lys Asp Ile Lys Ile Ile Asn Gln 8565 8570 8575 Ile Val Asp Asn Ala Ile Glu Leu Asn Asp Ala Met Gln Gly Leu Lys 8580 8585 8590 Glu His Val Ala Gln Leu Thr Ala Thr Thr Lys Asp Asn Ile Glu Tyr 8595 8600 8605 Leu Asn Ala Asp Glu Asp His Lys Leu Gln Tyr Asp Tyr Ala Ile Asn 8610 8615 8620 Leu Ala Asn Asn Val Leu Asp Lys Glu Asn Gly Thr Asn Lys Asp Ala 8625 8630 8635 8640 Asn Ile Ile Ile Gly Met Ile Gln Asn Met Asp Asp Ala Arg Ala Leu 8645 8650 8655 Leu Asn Gly Ile Glu Arg Leu Lys Asp Ala Gln Thr Lys Ala His Asn 8660 8665 8670 Asp Ile Lys Asp Thr Leu Lys Arg Gln Leu Asp Glu Ile Glu His Ala 8675 8680 8685 Asn Ala Thr Ser Asn Ser Lys Ala Gln Ala Lys Gln Met Val Asn Glu 8690 8695 8700 Glu Ala Arg Lys Ala Leu Ser Asn Ile Asn Asp Ala Thr Ser Asn Asp 8705 8710 8715 8720 Leu Val Asn Gln Ala Lys Asp Glu Gly Gln Ser Ala Ile Glu His Ile 8725 8730 8735 His Ala Asp Glu Leu Pro Lys Ala Lys Leu Asp Ala Asn Gln Met Ile 8740 8745 8750 Asp Gln Lys Val Glu Asp Ile Asn His Leu Ile Ser Gln Asn Pro Asn 8755 8760 8765 Leu Ser Asn Glu Glu Lys Asn Lys Leu Ile Ser Gln Ile Asn Lys Leu 8770 8775 8780 Val Asn Gly Ile Lys Asn Glu Ile Gln Gln Ala Ile Asn Lys Gln Gln 8785 8790 8795 8800 Ile Glu Asn Ala Thr Thr Lys Leu Asp Glu Val Ile Glu Thr Thr Lys 8805 8810 8815 Lys Leu Ile Ile Ala Lys Ala Glu Ala Lys Gln Met Ile Lys Glu Leu 8820 8825 8830 Ser Gln Lys Lys Arg Asp Ala Ile Asn Asn Asn Thr Asp Leu Thr Pro 8835 8840 8845 Ser Gln Lys Ala His Ala Leu Ala Asp Ile Asp Lys Thr Glu Lys Asp 8850 8855 8860 Ala Leu Gln His Ile Glu Asn Ser Asn Ser Ile Asp Asp Ile Asn Asn 8865 8870 8875 8880 Asn Lys Glu His Ala Phe Asn Thr Leu Ala His Ile Ile Ile Trp Asp 8885 8890 8895 Thr Asp Gln Gln Pro Leu Val Phe Glu Leu Pro Glu Leu Ser Leu Gln 8900 8905 8910 Asn Ala Leu Val Thr Ser Glu Val Val Val His Arg Asp Glu Thr Ile 8915 8920 8925 Ser Leu Glu Ser Ile Ile Gly Ala Met Thr Leu Thr Asp Glu Leu Lys 8930 8935 8940 Val Asn Ile Val Ser Leu Pro Asn Thr Asp Lys Val Ala Asp His Leu 8945 8950 8955 8960 Thr Ala Lys Val Lys Val Ile Leu Ala Asp Gly Ser Tyr Val Thr Val 8965 8970 8975 Asn Val Pro Val Lys Val Val Glu Lys Glu Leu Gln Ile Ala Lys Lys 8980 8985 8990 Asp Ala Ile Lys Thr Ile Asp Val Leu Val Lys Gln Lys Ile Lys Asp 8995 9000 9005 Ile Asp Ser Asn Asn Glu Leu Thr Ser Thr Gln Arg Glu Asp Ala Lys 9010 9015 9020 Ala Glu Ile Glu Arg Leu Lys Lys Gln Ala Ile Asp Lys Val Asn His 9025 9030 9035 9040 Ser Lys Ser Ile Lys Asp Ile Glu Thr Val Lys Arg Thr Asp Phe Glu 9045 9050 9055 Glu Ile Asp Gln Phe Asp Pro Lys Arg Phe Thr Leu Asn Lys Ala Lys 9060 9065

9070 Lys Asp Ile Ile Thr Asp Val Asn Thr Gln Ile Gln Asn Gly Phe Lys 9075 9080 9085 Glu Ile Glu Thr Ile Lys Gly Leu Thr Ser Asn Glu Lys Thr Gln Phe 9090 9095 9100 Asp Lys Gln Leu Thr Ala Leu Gln Lys Glu Phe Leu Glu Lys Val Glu 9105 9110 9115 9120 His Ala His Asn Leu Val Glu Leu Asn Gln Leu Gln Gln Glu Phe Asn 9125 9130 9135 Asn Arg Tyr Lys His Ile Leu Asn Gln Ala His Leu Leu Gly Glu Lys 9140 9145 9150 His Ile Ala Glu His Lys Leu Gly Tyr Val Val Val Asn Lys Thr Gln 9155 9160 9165 Gln Ile Leu Asn Asn Gln Ser Ala Ser Tyr Phe Ile Lys Gln Trp Ala 9170 9175 9180 Leu Asp Arg Ile Lys Gln Ile Gln Leu Glu Thr Met Asn Ser Ile Arg 9185 9190 9195 9200 Gly Ala His Thr Val Gln Asp Val His Lys Ala Leu Leu Gln Gly Ile 9205 9210 9215 Glu Gln Ile Leu Lys Val Asn Val Ser Ile Ile Asn Gln Ser Phe Asn 9220 9225 9230 Asp Ser Leu His Asn Phe Asn Tyr Leu His Ser Lys Phe Asp Ala Arg 9235 9240 9245 Leu Arg Glu Lys Asp Val Ala Asn His Ile Val Gln Thr Glu Thr Phe 9250 9255 9260 Lys Glu Val Leu Lys Gly Thr Gly Val Glu Pro Gly Lys Ile Asn Lys 9265 9270 9275 9280 Glu Thr Gln Gln Pro Lys Leu His Lys Asn Asp Asn Asp Ser Leu Phe 9285 9290 9295 Lys His Leu Val Asp Asn Phe Gly Lys Thr Val Gly Val Ile Thr Leu 9300 9305 9310 Thr Gly Leu Leu Ser Ser Phe Trp Leu Val Leu Ala Lys Arg Arg Lys 9315 9320 9325 Lys Glu Glu Glu Glu Lys Gln Ser Ile Lys Asn His His Lys Asp Ile 9330 9335 9340 Arg Leu Ser Asp Thr Asp Lys Ile Asp Pro Ile Val Ile Thr Lys Arg 9345 9350 9355 9360 Lys Ile Asp Lys Glu Glu Gln Ile Gln Asn Asp Asp Lys His Ser Ile 9365 9370 9375 Pro Val Ala Lys His Lys Lys Ser Lys Glu Lys Gln Leu Ser Glu Glu 9380 9385 9390 Asp Ile His Ser Ile Pro Val Val Lys Arg Lys Gln Asn Ser Asp Asn 9395 9400 9405 Lys Asp Thr Lys Gln Lys Lys Val Thr Ser Lys Lys Lys Lys Thr Pro 9410 9415 9420 Gln Ser Thr Lys Lys Val Val Lys Thr Lys Lys Arg Ser Lys Lys 9425 9430 9435 16 1115 PRT S. aureus 16 Met Arg Asp Lys Lys Gly Pro Val Asn Lys Arg Val Asp Phe Leu Ser 1 5 10 15 Asn Lys Leu Asn Lys Tyr Ser Ile Arg Lys Phe Thr Val Gly Thr Ala 20 25 30 Ser Ile Leu Ile Gly Ser Leu Met Tyr Leu Gly Thr Gln Gln Glu Ala 35 40 45 Glu Ala Ala Glu Asn Asn Ile Glu Asn Pro Thr Thr Leu Lys Asp Asn 50 55 60 Val Gln Ser Lys Glu Val Lys Ile Glu Glu Val Thr Asn Lys Asp Thr 65 70 75 80 Ala Pro Gln Gly Val Glu Ala Lys Ser Glu Val Thr Ser Asn Lys Asp 85 90 95 Thr Ile Glu His Glu Ala Ser Val Lys Ala Glu Asp Ile Ser Lys Lys 100 105 110 Glu Asp Thr Pro Lys Glu Val Ala Asn Val Ala Glu Val Gln Pro Lys 115 120 125 Ser Ser Val Thr His Asn Ala Glu Ala Pro Lys Val Arg Lys Ala Arg 130 135 140 Ser Val Asp Glu Gly Ser Phe Asp Ile Thr Arg Asp Ser Lys Asn Val 145 150 155 160 Val Glu Ser Thr Pro Ile Thr Ile Gln Gly Lys Glu His Phe Glu Gly 165 170 175 Tyr Gly Ser Val Asp Ile Gln Lys Asn Pro Thr Asp Leu Gly Val Ser 180 185 190 Glu Val Thr Arg Phe Asn Val Gly Asn Glu Ser Asn Gly Leu Ile Gly 195 200 205 Ala Leu Gln Leu Lys Asn Lys Ile Asp Phe Ser Lys Asp Phe Asn Phe 210 215 220 Lys Val Arg Val Ala Asn Asn His Gln Ser Asn Thr Thr Gly Ala Asp 225 230 235 240 Gly Trp Gly Phe Leu Phe Ser Lys Gly Asn Ala Glu Glu Tyr Leu Thr 245 250 255 Asn Gly Gly Ile Leu Gly Asp Lys Gly Leu Val Asn Ser Gly Gly Phe 260 265 270 Lys Ile Asp Thr Gly Tyr Ile Tyr Thr Ser Ser Met Asp Lys Thr Glu 275 280 285 Lys Gln Ala Gly Gln Gly Tyr Arg Gly Tyr Gly Ala Phe Val Lys Asn 290 295 300 Asp Ser Ser Gly Asn Ser Gln Met Val Gly Glu Asn Ile Asp Lys Ser 305 310 315 320 Lys Thr Asn Phe Leu Asn Tyr Ala Asp Asn Ser Thr Asn Thr Ser Asp 325 330 335 Gly Lys Phe His Gly Gln Arg Leu Asn Asp Val Ile Leu Thr Tyr Val 340 345 350 Ala Ser Thr Gly Lys Met Arg Ala Glu Tyr Ala Gly Lys Thr Trp Glu 355 360 365 Thr Ser Ile Thr Asp Leu Gly Leu Ser Lys Asn Gln Ala Tyr Asn Phe 370 375 380 Leu Ile Thr Ser Ser Gln Arg Trp Gly Leu Asn Gln Gly Ile Asn Ala 385 390 395 400 Asn Gly Trp Met Arg Thr Asp Leu Lys Gly Ser Glu Phe Thr Phe Thr 405 410 415 Pro Glu Ala Pro Lys Thr Ile Thr Glu Leu Glu Lys Lys Val Glu Glu 420 425 430 Ile Pro Phe Lys Lys Glu Arg Lys Phe Asn Pro Asp Leu Ala Pro Gly 435 440 445 Thr Glu Lys Val Thr Arg Glu Gly Gln Lys Gly Glu Lys Thr Ile Thr 450 455 460 Thr Pro Thr Leu Lys Asn Pro Leu Thr Gly Glu Ile Ile Ser Lys Gly 465 470 475 480 Glu Ser Lys Glu Glu Ile Thr Lys Asp Pro Ile Asn Glu Leu Thr Glu 485 490 495 Tyr Gly Pro Glu Thr Ile Ala Pro Gly His Arg Asp Glu Phe Asp Pro 500 505 510 Lys Leu Pro Thr Gly Glu Lys Glu Glu Val Pro Gly Lys Pro Gly Ile 515 520 525 Lys Asn Pro Glu Thr Gly Asp Val Val Arg Pro Pro Val Asp Ser Val 530 535 540 Thr Lys Tyr Gly Pro Val Lys Gly Asp Ser Ile Val Glu Lys Glu Glu 545 550 555 560 Ile Pro Phe Glu Lys Glu Arg Lys Phe Asn Pro Asp Leu Ala Pro Gly 565 570 575 Thr Glu Lys Val Thr Arg Glu Gly Gln Lys Gly Glu Lys Thr Ile Thr 580 585 590 Thr Pro Thr Leu Lys Asn Pro Leu Thr Gly Glu Ile Ile Ser Lys Gly 595 600 605 Glu Ser Lys Glu Glu Ile Thr Lys Asp Pro Ile Asn Glu Leu Thr Glu 610 615 620 Tyr Gly Pro Glu Thr Ile Ala Pro Gly His Arg Asp Glu Phe Asp Pro 625 630 635 640 Lys Leu Pro Thr Gly Glu Lys Glu Glu Val Pro Gly Lys Pro Gly Ile 645 650 655 Lys Asn Pro Glu Thr Gly Asp Val Val Arg Pro Pro Val Asp Ser Val 660 665 670 Thr Lys Tyr Gly Pro Val Lys Gly Asp Ser Ile Val Glu Lys Glu Glu 675 680 685 Ile Pro Phe Lys Lys Glu Arg Lys Phe Asn Pro Asp Leu Ala Pro Gly 690 695 700 Thr Glu Lys Val Thr Arg Glu Gly Gln Lys Gly Glu Lys Thr Ile Thr 705 710 715 720 Thr Pro Thr Leu Lys Asn Pro Leu Thr Gly Glu Ile Ile Ser Lys Gly 725 730 735 Glu Ser Lys Glu Glu Ile Thr Lys Asp Pro Ile Asn Glu Leu Thr Glu 740 745 750 Tyr Gly Pro Glu Thr Ile Thr Pro Gly His Arg Asp Glu Phe Asp Pro 755 760 765 Lys Leu Pro Thr Gly Glu Lys Glu Glu Val Pro Gly Lys Pro Gly Ile 770 775 780 Lys Asn Pro Glu Thr Gly Asp Val Val Arg Pro Pro Val Asp Ser Val 785 790 795 800 Thr Lys Tyr Gly Pro Val Lys Gly Asp Ser Ile Val Glu Lys Glu Glu 805 810 815 Ile Pro Phe Glu Lys Glu Arg Lys Phe Asn Pro Asp Leu Ala Pro Gly 820 825 830 Thr Glu Lys Val Thr Arg Glu Gly Gln Lys Gly Glu Lys Thr Ile Thr 835 840 845 Thr Pro Thr Leu Lys Asn Pro Leu Thr Gly Glu Ile Ile Ser Lys Gly 850 855 860 Glu Ser Lys Glu Glu Ile Thr Lys Asp Pro Val Asn Glu Leu Thr Glu 865 870 875 880 Phe Gly Gly Glu Lys Ile Pro Gln Gly His Lys Asp Ile Phe Asp Pro 885 890 895 Asn Leu Pro Thr Asp Gln Thr Glu Lys Val Pro Gly Lys Pro Gly Ile 900 905 910 Lys Asn Pro Asp Thr Gly Lys Val Ile Glu Glu Pro Val Asp Asp Val 915 920 925 Ile Lys His Gly Pro Lys Thr Gly Thr Pro Glu Thr Lys Thr Val Glu 930 935 940 Ile Pro Phe Glu Thr Lys Arg Glu Phe Asn Pro Lys Leu Gln Pro Gly 945 950 955 960 Glu Glu Arg Val Lys Gln Glu Gly Gln Pro Gly Ser Lys Thr Ile Thr 965 970 975 Thr Pro Ile Thr Val Asn Pro Leu Thr Gly Glu Lys Val Gly Glu Gly 980 985 990 Gln Pro Thr Glu Glu Ile Thr Lys Gln Pro Val Asp Lys Ile Val Glu 995 1000 1005 Phe Gly Gly Glu Lys Pro Lys Asp Pro Lys Gly Pro Glu Asn Pro Glu 1010 1015 1020 Lys Pro Ser Arg Pro Thr His Pro Ser Gly Pro Val Asn Pro Asn Asn 1025 1030 1035 1040 Pro Gly Leu Ser Lys Asp Arg Ala Lys Pro Asn Gly Pro Val His Ser 1045 1050 1055 Met Asp Lys Asn Asp Lys Val Lys Lys Ser Lys Ile Ala Lys Glu Ser 1060 1065 1070 Val Ala Asn Gln Glu Lys Lys Arg Ala Glu Leu Pro Lys Thr Gly Leu 1075 1080 1085 Glu Ser Thr Gln Lys Gly Leu Ile Phe Ser Ser Ile Ile Gly Ile Ala 1090 1095 1100 Gly Leu Met Leu Leu Ala Arg Arg Arg Lys Asn 1105 1110 1115 17 1469 PRT S. epidermidis 17 Met Gly Lys Arg Arg Gln Gly Pro Ile Asn Lys Lys Val Asp Phe Leu 1 5 10 15 Pro Asn Lys Leu Asn Lys Tyr Ser Ile Arg Lys Phe Thr Val Gly Thr 20 25 30 Ala Ser Ile Leu Leu Gly Ser Thr Leu Ile Phe Gly Ser Ser Ser His 35 40 45 Glu Ala Lys Ala Ala Glu Glu Lys Gln Val Asp Pro Ile Thr Gln Ala 50 55 60 Asn Gln Asn Asp Ser Ser Glu Arg Ser Leu Glu Asn Thr Asn Gln Pro 65 70 75 80 Thr Val Asn Asn Glu Ala Pro Gln Met Ser Ser Thr Leu Gln Ala Glu 85 90 95 Glu Gly Ser Asn Ala Glu Ala Pro Asn Val Pro Thr Ile Lys Ala Asn 100 105 110 Ser Asp Asn Asp Thr Gln Thr Gln Phe Ser Glu Ala Pro Thr Arg Asn 115 120 125 Asp Leu Ala Arg Lys Glu Asp Ile Pro Ala Val Ser Lys Asn Glu Glu 130 135 140 Leu Gln Ser Ser Gln Pro Asn Thr Asp Ser Lys Ile Glu Pro Thr Thr 145 150 155 160 Ser Glu Pro Val Asn Leu Asn Tyr Ser Ser Pro Phe Met Ser Leu Leu 165 170 175 Ser Met Pro Ala Asp Ser Ser Ser Asn Asn Thr Lys Asn Thr Ile Asp 180 185 190 Ile Pro Pro Thr Thr Val Lys Gly Arg Asp Asn Tyr Asp Phe Tyr Gly 195 200 205 Arg Val Asp Ile Gln Ser Asn Pro Thr Asp Leu Asn Ala Thr Asn Leu 210 215 220 Thr Arg Tyr Asn Tyr Gly Gln Pro Pro Gly Thr Thr Thr Ala Gly Ala 225 230 235 240 Val Gln Phe Lys Asn Gln Val Ser Phe Asp Lys Asp Phe Asp Phe Asn 245 250 255 Ile Arg Val Ala Asn Asn Arg Gln Ser Asn Thr Thr Gly Ala Asp Gly 260 265 270 Trp Gly Phe Met Phe Ser Lys Lys Asp Gly Asp Asp Phe Leu Lys Asn 275 280 285 Gly Gly Ile Leu Arg Glu Lys Gly Thr Pro Ser Ala Ala Gly Phe Arg 290 295 300 Ile Asp Thr Gly Tyr Tyr Asn Asn Asp Pro Leu Asp Lys Ile Gln Lys 305 310 315 320 Gln Ala Gly Gln Gly Tyr Arg Gly Tyr Gly Thr Phe Val Lys Asn Asp 325 330 335 Ser Gln Gly Asn Thr Ser Lys Val Gly Ser Gly Thr Pro Ser Thr Asp 340 345 350 Phe Leu Asn Tyr Ala Asp Asn Thr Thr Asn Asp Leu Asp Gly Lys Phe 355 360 365 His Gly Gln Lys Leu Asn Asn Val Asn Leu Lys Tyr Asn Ala Ser Asn 370 375 380 Gln Thr Phe Thr Ala Thr Tyr Ala Gly Lys Thr Trp Thr Ala Thr Leu 385 390 395 400 Ser Glu Leu Gly Leu Ser Pro Thr Asp Ser Tyr Asn Phe Leu Val Thr 405 410 415 Ser Ser Gln Tyr Gly Asn Gly Asn Ser Gly Thr Tyr Ala Asp Gly Val 420 425 430 Met Arg Ala Asp Leu Asp Gly Ala Thr Leu Thr Tyr Thr Pro Lys Ala 435 440 445 Val Asp Gly Asp Pro Ile Thr Ser Thr Lys Glu Ile Pro Phe Asn Lys 450 455 460 Lys Arg Glu Phe Asp Pro Asn Leu Ala Pro Gly Thr Glu Lys Val Val 465 470 475 480 Gln Lys Gly Glu Pro Gly Ile Glu Thr Thr Thr Thr Pro Thr Tyr Val 485 490 495 Asn Pro Asn Thr Gly Glu Lys Val Gly Glu Gly Thr Pro Thr Thr Lys 500 505 510 Ile Thr Lys Gln Pro Val Asp Glu Ile Val His Tyr Gly Gly Glu Glu 515 520 525 Ile Lys Pro Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Lys Gly 530 535 540 Ser Gln Thr Thr Gln Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr 545 550 555 560 Gly Glu Val Val Thr Pro Pro Val Asp Asp Val Thr Lys Tyr Gly Pro 565 570 575 Val Asp Gly Asp Pro Ile Thr Ser Thr Glu Glu Ile Pro Phe Asp Lys 580 585 590 Lys Arg Glu Phe Asn Pro Asp Leu Lys Pro Gly Glu Glu Arg Val Lys 595 600 605 Gln Lys Gly Glu Pro Gly Thr Lys Thr Ile Thr Thr Pro Thr Thr Lys 610 615 620 Asn Pro Leu Thr Gly Glu Lys Val Gly Glu Gly Glu Pro Thr Glu Lys 625 630 635 640 Ile Thr Lys Gln Pro Val Asp Glu Ile Thr Glu Tyr Gly Gly Glu Glu 645 650 655 Ile Lys Pro Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Lys Gly 660 665 670 Ser Gln Glu Asp Val Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr 675 680 685 Gly Glu Val Val Thr Pro Pro Val Asp Asp Val Thr Lys Tyr Gly Pro 690 695 700 Val Asp Gly Asp Pro Ile Thr Ser Thr Glu Glu Ile Pro Phe Asp Lys 705 710 715 720 Lys Arg Glu Phe Asp Pro Asn Leu Ala Pro Gly Thr Glu Lys Val Val 725 730 735 Gln Lys Gly Glu Pro Gly Thr Lys Thr Ile Thr Thr Pro Thr Thr Lys 740 745 750 Asn Pro Leu Thr Gly Glu Lys Val Gly Glu Gly Glu Pro Thr Glu Lys 755 760 765 Ile Thr Lys Gln Pro Val Asp Glu Ile Val His Tyr Gly Gly Glu Glu 770 775 780 Ile Lys Pro Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Lys Gly 785 790 795 800 Ser Gln Glu Asp Val Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr 805 810 815 Gly Glu Val Val Thr Pro Pro Val Asp Asp Val Thr Lys Tyr Gly Pro 820 825 830 Val Asp Gly Asp Pro Ile Thr Ser Thr Glu Glu Ile Pro Phe Asp Lys 835 840 845 Lys Arg Glu Phe Asn Pro Asp Leu Lys Pro Gly Glu Glu Arg Val Lys 850 855 860 Gln Lys Gly Glu Pro Gly Thr Lys Thr Ile Thr Thr Pro Thr Thr Lys 865 870 875 880 Asn Pro Leu Thr Gly Glu Lys Val Gly Glu Gly Glu Pro Thr Glu Lys 885 890 895 Val Thr Lys Gln Pro Val Asp Glu Ile Val His Tyr Gly Gly Glu Glu 900 905 910 Ile Lys Pro Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Lys Gly 915 920 925 Ser Gln Glu Asp Val Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr 930 935 940 Gly Glu Val Val Thr Pro Pro Val Asp Asp Val Thr Lys Tyr Gly Pro 945

950 955 960 Val Asp Gly Asp Pro Ile Thr Ser Thr Glu Glu Ile Pro Phe Asp Lys 965 970 975 Lys Arg Glu Phe Asp Pro Asn Leu Ala Pro Gly Thr Glu Lys Val Val 980 985 990 Gln Lys Gly Glu Pro Gly Thr Lys Thr Ile Thr Thr Pro Thr Thr Lys 995 1000 1005 Asn Pro Leu Thr Gly Glu Lys Val Gly Glu Gly Glu Pro Thr Glu Lys 1010 1015 1020 Ile Thr Lys Gln Pro Val Asp Glu Ile Val His Tyr Gly Gly Glu Glu 1025 1030 1035 1040 Ile Lys Pro Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Lys Gly 1045 1050 1055 Ser Gln Thr Thr Gln Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr 1060 1065 1070 Gly Glu Val Val Thr Pro Pro Val Asp Asp Val Thr Lys Tyr Gly Pro 1075 1080 1085 Val Asp Gly Asp Pro Ile Thr Ser Thr Glu Glu Ile Pro Phe Asp Lys 1090 1095 1100 Lys Arg Glu Phe Asp Pro Asn Leu Ala Pro Gly Thr Glu Lys Val Val 1105 1110 1115 1120 Gln Lys Gly Glu Pro Gly Thr Lys Thr Ile Thr Thr Pro Thr Thr Lys 1125 1130 1135 Asn Pro Leu Thr Gly Glu Lys Val Gly Glu Gly Glu Pro Thr Glu Lys 1140 1145 1150 Ile Thr Lys Gln Pro Val Asp Glu Ile Val His Tyr Gly Gly Glu Gln 1155 1160 1165 Ile Pro Gln Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Val Asp 1170 1175 1180 Ser Lys Thr Glu Val Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr 1185 1190 1195 1200 Gly Glu Val Val Thr Pro Pro Val Asp Asp Val Thr Lys Tyr Gly Pro 1205 1210 1215 Lys Val Gly Asn Pro Ile Thr Ser Thr Glu Glu Ile Pro Phe Asp Lys 1220 1225 1230 Lys Arg Val Phe Asn Pro Asp Leu Lys Pro Gly Glu Glu Arg Val Lys 1235 1240 1245 Gln Lys Gly Glu Pro Gly Thr Lys Thr Ile Thr Thr Pro Ile Leu Val 1250 1255 1260 Asn Pro Ile Thr Gly Glu Lys Val Gly Glu Gly Lys Ser Thr Glu Lys 1265 1270 1275 1280 Val Thr Lys Gln Pro Val Asp Glu Ile Val Glu Tyr Gly Pro Thr Lys 1285 1290 1295 Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly 1300 1305 1310 Lys Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly Thr Pro Ala Glu 1315 1320 1325 Pro Gly Lys Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly Lys Pro 1330 1335 1340 Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly 1345 1350 1355 1360 Thr Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly Lys Pro Ala Glu 1365 1370 1375 Pro Gly Lys Pro Ala Glu Pro Gly Thr Pro Ala Glu Pro Gly Lys Pro 1380 1385 1390 Ala Glu Pro Gly Thr Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly 1395 1400 1405 Thr Pro Thr Gln Ser Gly Ala Pro Glu Gln Pro Asn Arg Ser Met His 1410 1415 1420 Ser Thr Asp Asn Lys Asn Gln Leu Pro Asp Thr Gly Glu Asn Arg Gln 1425 1430 1435 1440 Ala Asn Glu Gly Thr Leu Val Gly Ser Leu Leu Ala Ile Val Gly Ser 1445 1450 1455 Leu Phe Ile Phe Gly Arg Arg Lys Lys Gly Asn Glu Lys 1460 1465 18 167 PRT S. aureus 18 Met Lys Lys Leu Tyr Thr Ser Tyr Gly Thr Tyr Gly Phe Leu His Gln 1 5 10 15 Ile Lys Ile Asn Asn Pro Thr His Gln Leu Phe Gln Phe Ser Ala Ser 20 25 30 Asp Thr Ser Val Ile Phe Glu Glu Thr Asp Gly Glu Thr Val Leu Lys 35 40 45 Ser Pro Ser Ile Tyr Glu Val Ile Lys Glu Ile Gly Glu Phe Ser Glu 50 55 60 His His Phe Tyr Cys Ala Ile Phe Ile Pro Ser Thr Glu Asp His Ala 65 70 75 80 Tyr Gln Leu Glu Lys Lys Leu Ile Ser Val Asp Asp Asn Phe Arg Asn 85 90 95 Phe Gly Gly Phe Lys Ser Tyr Arg Leu Leu Arg Pro Ala Lys Gly Thr 100 105 110 Thr Tyr Lys Ile Tyr Phe Gly Phe Ala Asp Arg His Ala Tyr Glu Asp 115 120 125 Phe Lys Gln Ser Asp Ala Phe Asn Asp His Phe Ser Lys Asp Ala Leu 130 135 140 Ser His Tyr Phe Gly Ser Ser Gly Gln His Ser Ser Tyr Phe Glu Arg 145 150 155 160 Tyr Leu Tyr Pro Ile Lys Glu 165 19 167 PRT S. epidermidis 19 Met Tyr Leu Tyr Thr Ser Tyr Gly Thr Tyr Gln Phe Leu Asn Gln Ile 1 5 10 15 Lys Leu Asn His Gln Glu Arg Ser Leu Phe Gln Phe Ser Thr Asn Asp 20 25 30 Ser Ser Ile Ile Leu Glu Glu Ser Glu Gly Lys Ser Ile Leu Lys His 35 40 45 Pro Ser Ala Tyr Gln Val Ile Asp Ser Thr Gly Glu Phe Asn Glu His 50 55 60 His Phe Tyr Ser Ala Ile Phe Val Pro Thr Ser Glu Asp His Arg Gln 65 70 75 80 Gln Leu Glu Lys Lys Leu Leu Leu Val Asp Val Pro Leu Arg Asn Phe 85 90 95 Gly Gly Phe Lys Ser Tyr Arg Leu Leu Lys Pro Thr Glu Gly Ser Thr 100 105 110 Tyr Lys Ile Tyr Phe Gly Phe Ala Asn Arg Thr Ala Tyr Glu Asp Phe 115 120 125 Lys Ala Ser Asp Ile Phe Asn Glu Asn Phe Ser Lys Asp Ala Leu Ser 130 135 140 Gln Tyr Phe Gly Ala Ser Gly Gln His Ser Ser Tyr Phe Glu Arg Tyr 145 150 155 160 Leu Tyr Pro Ile Glu Asp His 165 20 1141 PRT S. aureus 20 Met Ile Asn Arg Asp Asn Lys Lys Ala Ile Thr Lys Lys Gly Met Ile 1 5 10 15 Ser Asn Arg Leu Asn Lys Phe Ser Ile Arg Lys Tyr Thr Val Gly Thr 20 25 30 Ala Ser Ile Leu Val Gly Thr Thr Leu Ile Phe Gly Leu Gly Asn Gln 35 40 45 Glu Ala Lys Ala Ala Glu Asn Thr Ser Thr Glu Asn Ala Lys Gln Asp 50 55 60 Asp Ala Thr Thr Ser Asp Asn Lys Glu Val Val Ser Glu Thr Glu Asn 65 70 75 80 Asn Ser Thr Thr Glu Asn Asp Ser Thr Asn Pro Ile Lys Lys Glu Thr 85 90 95 Asn Thr Asp Ser Gln Pro Glu Ala Lys Glu Glu Ser Thr Thr Ser Ser 100 105 110 Thr Gln Gln Gln Gln Asn Asn Val Thr Ala Thr Thr Glu Thr Lys Pro 115 120 125 Gln Asn Ile Glu Lys Glu Asn Val Lys Pro Ser Thr Asp Lys Thr Ala 130 135 140 Thr Glu Asp Thr Ser Val Ile Leu Glu Glu Lys Lys Ala Pro Asn Tyr 145 150 155 160 Thr Asn Asn Asp Val Thr Thr Lys Pro Ser Thr Ser Glu Ile Gln Thr 165 170 175 Lys Pro Thr Thr Pro Gln Glu Ser Thr Asn Ile Glu Asn Ser Gln Pro 180 185 190 Gln Pro Thr Pro Ser Lys Val Asp Asn Gln Val Thr Asp Ala Thr Asn 195 200 205 Pro Lys Glu Pro Val Asn Val Ser Lys Glu Glu Leu Lys Asn Asn Pro 210 215 220 Glu Lys Leu Lys Glu Leu Val Arg Asn Asp Asn Asn Thr Asp Arg Ser 225 230 235 240 Thr Lys Pro Val Ala Thr Ala Pro Thr Ser Val Ala Pro Lys Arg Leu 245 250 255 Asn Ala Lys Met Arg Phe Ala Val Ala Gln Pro Ala Ala Val Ala Ser 260 265 270 Asn Asn Val Asn Asp Leu Ile Thr Val Thr Lys Gln Thr Ile Lys Val 275 280 285 Gly Asp Gly Lys Asp Asn Val Ala Ala Ala His Asp Gly Lys Asp Ile 290 295 300 Glu Tyr Asp Thr Glu Phe Thr Ile Asp Asn Lys Val Lys Lys Gly Asp 305 310 315 320 Thr Met Thr Ile Asn Tyr Asp Lys Asn Val Ile Pro Ser Asp Leu Thr 325 330 335 Asp Lys Asn Asp Pro Ile Asp Ile Thr Asp Pro Ser Gly Glu Val Ile 340 345 350 Ala Lys Gly Thr Phe Asp Lys Ala Thr Lys Gln Ile Thr Tyr Thr Phe 355 360 365 Thr Asp Tyr Val Asp Lys Tyr Glu Asp Ile Lys Ala Arg Leu Thr Leu 370 375 380 Tyr Ser Tyr Ile Asp Lys Gln Ala Val Pro Asn Glu Thr Ser Leu Asn 385 390 395 400 Leu Thr Phe Ala Thr Ala Gly Lys Glu Thr Ser Gln Asn Val Ser Val 405 410 415 Asp Tyr Gln Asp Pro Met Val His Gly Asp Ser Asn Ile Gln Ser Ile 420 425 430 Phe Thr Lys Leu Asp Glu Asn Lys Gln Thr Ile Glu Gln Gln Ile Tyr 435 440 445 Val Asn Pro Leu Lys Lys Thr Ala Thr Asn Thr Lys Val Asp Ile Ala 450 455 460 Gly Ser Gln Val Asp Asp Tyr Gly Asn Ile Lys Leu Gly Asn Gly Ser 465 470 475 480 Thr Ile Ile Asp Gln Asn Thr Glu Ile Lys Val Tyr Lys Val Asn Pro 485 490 495 Asn Gln Gln Leu Pro Gln Ser Asn Arg Ile Tyr Asp Phe Ser Gln Tyr 500 505 510 Glu Asp Val Thr Ser Gln Phe Asp Asn Lys Lys Ser Phe Ser Asn Asn 515 520 525 Val Ala Thr Leu Asp Phe Gly Asp Ile Asn Ser Ala Tyr Ile Ile Lys 530 535 540 Val Val Ser Lys Tyr Thr Pro Thr Ser Asp Gly Glu Leu Asp Ile Ala 545 550 555 560 Gln Gly Thr Ser Met Arg Thr Thr Asp Lys Tyr Gly Tyr Tyr Asn Tyr 565 570 575 Ala Gly Tyr Ser Asn Phe Ile Val Thr Ser Asn Asp Thr Gly Gly Gly 580 585 590 Asp Gly Thr Val Lys Pro Glu Glu Lys Leu Tyr Lys Ile Gly Asp Tyr 595 600 605 Val Trp Glu Asp Val Asp Lys Asp Gly Val Gln Gly Thr Asp Ser Lys 610 615 620 Glu Lys Pro Met Ala Asn Val Leu Val Thr Leu Thr Tyr Pro Asp Gly 625 630 635 640 Thr Thr Lys Ser Val Arg Thr Asp Ala Asn Gly His Tyr Glu Phe Gly 645 650 655 Gly Leu Lys Asp Gly Glu Thr Tyr Thr Val Lys Phe Glu Thr Pro Ala 660 665 670 Gly Tyr Leu Pro Thr Lys Val Asn Gly Thr Thr Asp Gly Glu Lys Asp 675 680 685 Ser Asn Gly Ser Ser Ile Thr Val Lys Ile Asn Gly Lys Asp Asp Met 690 695 700 Ser Leu Asp Thr Gly Phe Tyr Lys Glu Pro Lys Tyr Asn Leu Gly Asp 705 710 715 720 Tyr Val Trp Glu Asp Thr Asn Lys Asp Gly Ile Gln Asp Ala Asn Glu 725 730 735 Pro Gly Ile Lys Asp Val Lys Val Thr Leu Lys Asp Ser Thr Gly Lys 740 745 750 Val Ile Gly Thr Thr Thr Thr Asp Ala Ser Gly Lys Tyr Lys Phe Thr 755 760 765 Asp Leu Asp Asn Gly Asn Tyr Thr Val Glu Phe Glu Thr Pro Ala Gly 770 775 780 Tyr Thr Pro Thr Val Lys Asn Thr Thr Ala Glu Asp Lys Asp Ser Asn 785 790 795 800 Gly Leu Thr Thr Thr Gly Val Ile Lys Asp Ala Asp Asn Met Thr Leu 805 810 815 Asp Ser Gly Phe Tyr Lys Thr Pro Lys Tyr Ser Leu Gly Asp Tyr Val 820 825 830 Trp Tyr Asp Ser Asn Lys Asp Gly Lys Gln Asp Ser Thr Glu Lys Gly 835 840 845 Ile Lys Asp Val Lys Val Thr Leu Leu Asn Glu Lys Gly Glu Val Ile 850 855 860 Gly Thr Thr Lys Thr Asp Glu Asn Gly Lys Tyr Arg Phe Asp Asn Leu 865 870 875 880 Asp Ser Gly Lys Tyr Lys Val Ile Phe Glu Lys Pro Ala Gly Leu Thr 885 890 895 Gln Thr Val Thr Asn Thr Thr Glu Asp Asp Lys Asp Ala Asp Gly Gly 900 905 910 Glu Val Asp Val Thr Ile Thr Asp His Asp Asp Phe Ile Leu Asp Asn 915 920 925 Gly Tyr Phe Glu Glu Asp Thr Ser Asp Ser Asp Ser Asp Ser Asp Ser 930 935 940 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 945 950 955 960 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 965 970 975 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 980 985 990 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 995 1000 1005 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 1010 1015 1020 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 1025 1030 1035 1040 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 1045 1050 1055 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 1060 1065 1070 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ala Gly Lys His Thr Pro Val 1075 1080 1085 Lys Pro Met Ser Thr Thr Lys Asp His His Asn Lys Ala Lys Ala Leu 1090 1095 1100 Pro Glu Thr Gly Ser Glu Asn Asn Gly Ser Asn Asn Ala Thr Leu Phe 1105 1110 1115 1120 Gly Gly Leu Phe Ala Ala Leu Gly Ser Leu Leu Leu Phe Gly Arg Arg 1125 1130 1135 Lys Lys Gln Asn Lys 1140 21 1056 PRT S. epidermidis 21 Met Ile Asn Lys Lys Asn Asn Leu Leu Thr Lys Lys Lys Pro Ile Ala 1 5 10 15 Asn Lys Ser Asn Lys Tyr Ala Ile Arg Lys Phe Thr Val Gly Thr Ala 20 25 30 Ser Ile Val Ile Gly Ala Thr Leu Leu Phe Gly Leu Gly His Asn Glu 35 40 45 Ala Lys Ala Glu Glu Asn Ser Val Gln Asp Val Lys Asp Ser Asn Thr 50 55 60 Asp Asp Glu Leu Ser Asp Ser Asn Asp Gln Ser Ser Asp Glu Glu Lys 65 70 75 80 Asn Asp Val Ile Asn Asn Asn Gln Ser Ile Asn Thr Asp Asp Asn Asn 85 90 95 Gln Ile Ile Lys Lys Glu Glu Thr Asn Asn Tyr Asp Gly Ile Glu Lys 100 105 110 Arg Ser Glu Asp Arg Thr Glu Ser Thr Thr Asn Val Asp Glu Asn Glu 115 120 125 Ala Thr Phe Leu Gln Lys Thr Pro Gln Asp Asn Thr His Leu Thr Glu 130 135 140 Glu Glu Val Lys Glu Ser Ser Ser Val Glu Ser Ser Asn Ser Ser Ile 145 150 155 160 Asp Thr Ala Gln Gln Pro Ser His Thr Thr Ile Asn Arg Glu Glu Ser 165 170 175 Val Gln Thr Ser Asp Asn Val Glu Asp Ser His Val Ser Asp Phe Ala 180 185 190 Asn Ser Lys Ile Lys Glu Ser Asn Thr Glu Ser Gly Lys Glu Glu Asn 195 200 205 Thr Ile Glu Gln Pro Asn Lys Val Lys Glu Asp Ser Thr Thr Ser Gln 210 215 220 Pro Ser Gly Tyr Thr Asn Ile Asp Glu Lys Ile Ser Asn Gln Asp Glu 225 230 235 240 Leu Leu Asn Leu Pro Ile Asn Glu Tyr Glu Asn Lys Ala Arg Pro Leu 245 250 255 Ser Thr Thr Ser Ala Gln Pro Ser Ile Lys Arg Val Thr Val Asn Gln 260 265 270 Leu Ala Ala Glu Gln Gly Ser Asn Val Asn His Leu Ile Lys Val Thr 275 280 285 Asp Gln Ser Ile Thr Glu Gly Tyr Asp Asp Ser Glu Gly Val Ile Lys 290 295 300 Ala His Asp Ala Glu Asn Leu Ile Tyr Asp Val Thr Phe Glu Val Asp 305 310 315 320 Asp Lys Val Lys Ser Gly Asp Thr Met Thr Val Asp Ile Asp Lys Asn 325 330 335 Thr Val Pro Ser Asp Leu Thr Asp Ser Phe Thr Ile Pro Lys Ile Lys 340 345 350 Asp Asn Ser Gly Glu Ile Ile Ala Thr Gly Thr Tyr Asp Asn Lys Asn 355 360 365 Lys Gln Ile Thr Tyr Thr Phe Thr Asp Tyr Val Asp Lys Tyr Glu Asn 370 375 380 Ile Lys Ala His Leu Lys Leu Thr Ser Tyr Ile Asp Lys Ser Lys Val 385 390 395 400 Pro Asn Asn Asn Thr Lys Leu Asp Val Glu Tyr Lys Thr Ala Leu Ser 405 410 415 Ser Val Asn Lys Thr Ile Thr Val Glu Tyr Gln Arg Pro Asn Glu Asn 420 425 430 Arg Thr Ala Asn Leu Gln Ser

Met Phe Thr Asn Ile Asp Thr Lys Asn 435 440 445 His Thr Val Glu Gln Thr Ile Tyr Ile Asn Pro Leu Arg Tyr Ser Ala 450 455 460 Lys Glu Thr Asn Val Asn Ile Ser Gly Asn Gly Asp Glu Gly Ser Thr 465 470 475 480 Ile Ile Asp Asp Ser Thr Ile Ile Lys Val Tyr Lys Val Gly Asp Asn 485 490 495 Gln Asn Leu Pro Asp Ser Asn Arg Ile Tyr Asp Tyr Ser Glu Tyr Glu 500 505 510 Asp Val Thr Asn Asp Asp Tyr Ala Gln Leu Gly Asn Asn Asn Asp Val 515 520 525 Asn Ile Asn Phe Gly Asn Ile Asp Ser Pro Tyr Ile Ile Lys Val Ile 530 535 540 Ser Lys Tyr Asp Pro Asn Lys Asp Asp Tyr Thr Thr Ile Gln Gln Thr 545 550 555 560 Val Thr Met Gln Thr Thr Ile Asn Glu Tyr Thr Gly Glu Phe Arg Thr 565 570 575 Ala Ser Tyr Asp Asn Thr Ile Ala Phe Ser Thr Ser Ser Gly Gln Gly 580 585 590 Gln Gly Asp Leu Pro Pro Glu Lys Thr Tyr Lys Ile Gly Asp Tyr Val 595 600 605 Trp Glu Asp Val Asp Lys Asp Gly Ile Gln Asn Thr Asn Asp Asn Glu 610 615 620 Lys Pro Leu Ser Asn Val Leu Val Thr Leu Thr Tyr Pro Asp Gly Thr 625 630 635 640 Ser Lys Ser Val Arg Thr Asp Glu Asp Gly Lys Tyr Gln Phe Asp Gly 645 650 655 Leu Lys Asn Gly Leu Thr Tyr Lys Ile Thr Phe Glu Thr Pro Glu Gly 660 665 670 Tyr Thr Pro Thr Leu Lys His Ser Gly Thr Asn Pro Ala Leu Asp Ser 675 680 685 Glu Gly Asn Ser Val Trp Val Thr Ile Asn Gly Gln Asp Asp Met Thr 690 695 700 Ile Asp Ser Gly Phe Tyr Gln Thr Pro Lys Tyr Ser Leu Gly Asn Tyr 705 710 715 720 Val Trp Tyr Asp Thr Asn Lys Asp Gly Ile Gln Gly Asp Asp Glu Lys 725 730 735 Gly Ile Ser Gly Val Lys Val Thr Leu Lys Asp Glu Asn Gly Asn Ile 740 745 750 Ile Ser Thr Thr Thr Thr Asp Glu Asn Gly Lys Tyr Gln Phe Asp Asn 755 760 765 Leu Asn Ser Gly Asn Tyr Ile Val His Phe Asp Lys Pro Ser Gly Met 770 775 780 Thr Gln Thr Thr Thr Asp Ser Gly Asp Asp Asp Glu Gln Asp Ala Asp 785 790 795 800 Gly Glu Glu Val His Val Thr Ile Thr Asp His Asp Asp Phe Ser Ile 805 810 815 Asp Asn Gly Tyr Tyr Asp Asp Glu Ser Asp Ser Asp Ser Asp Ser Asp 820 825 830 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 835 840 845 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 850 855 860 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 865 870 875 880 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 885 890 895 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 900 905 910 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 915 920 925 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 930 935 940 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 945 950 955 960 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 965 970 975 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 980 985 990 Ser Asp Ser Asp Ser Asp Ser Asp Asn Asp Ser Asp Leu Gly Asn Ser 995 1000 1005 Ser Asp Lys Ser Thr Lys Asp Lys Leu Pro Asp Thr Gly Ala Asn Glu 1010 1015 1020 Asp Tyr Gly Ser Lys Gly Thr Leu Leu Gly Thr Leu Phe Ala Gly Leu 1025 1030 1035 1040 Gly Ala Leu Leu Leu Gly Lys Arg Arg Lys Asn Arg Lys Asn Lys Asn 1045 1050 1055 22 486 PRT S. aureus 22 Met Ser Asn Asn Phe Lys Asp Asp Phe Glu Lys Asn Arg Gln Ser Ile 1 5 10 15 Asp Thr Asn Ser His Gln Asp His Thr Glu Asp Val Glu Lys Asp Gln 20 25 30 Ser Glu Leu Glu His Gln Asp Thr Ile Glu Asn Thr Glu Gln Gln Phe 35 40 45 Pro Pro Arg Asn Ala Gln Arg Arg Lys Arg Arg Arg Asp Leu Ala Thr 50 55 60 Asn His Asn Lys Gln Val His Asn Glu Ser Gln Thr Ser Glu Asp Asn 65 70 75 80 Val Gln Asn Glu Ala Gly Thr Ile Asp Asp Arg Gln Val Glu Ser Ser 85 90 95 His Ser Thr Glu Ser Gln Glu Pro Ser His Gln Asp Ser Thr Pro Gln 100 105 110 His Glu Glu Glu Tyr Tyr Asn Lys Asn Ala Phe Ala Met Asp Lys Ser 115 120 125 His Pro Glu Pro Ile Glu Asp Asn Asp Lys His Glu Thr Ile Lys Asp 130 135 140 Ala Glu Asn Asn Thr Glu His Ser Thr Val Ser Asp Lys Ser Ile Ala 145 150 155 160 Glu Gln Ser Gln Gln Pro Lys Pro Tyr Phe Ala Thr Gly Ala Asn Gln 165 170 175 Ala Asn Thr Ser Lys Asp Lys His Asp Asp Val Thr Val Lys Gln Asp 180 185 190 Lys Asp Glu Ser Lys Asp His His Ser Gly Lys Lys Gly Ala Ala Ile 195 200 205 Gly Ala Gly Thr Ala Gly Val Ala Gly Ala Ala Gly Ala Met Gly Val 210 215 220 Ser Lys Ala Lys Lys His Ser Asn Asp Ala Gln Asn Lys Ser Asn Ser 225 230 235 240 Asp Lys Ser Asn Asn Ser Thr Glu Asp Lys Ala Ser Gln Asp Lys Ser 245 250 255 Lys Asp His His Asn Gly Lys Lys Gly Ala Ala Ile Gly Ala Gly Thr 260 265 270 Ala Gly Leu Ala Gly Gly Ala Ala Ser Lys Ser Ala Ser Ala Ala Ser 275 280 285 Lys Pro His Ala Ser Asn Asn Ala Ser Gln Asn His Asp Glu His Asp 290 295 300 Asn His Asp Arg Asp Lys Glu Arg Lys Lys Gly Gly Met Ala Lys Val 305 310 315 320 Leu Leu Pro Leu Ile Ala Ala Val Leu Ile Ile Gly Ala Leu Ala Ile 325 330 335 Phe Gly Gly Met Ala Leu Asn Asn His Asn Asn Gly Thr Lys Glu Asn 340 345 350 Lys Ile Ala Asn Thr Asn Lys Asn Asn Ala Asp Glu Ser Lys Asp Lys 355 360 365 Asp Thr Ser Lys Asp Ala Ser Lys Asp Lys Ser Lys Ser Thr Asp Ser 370 375 380 Asp Lys Ser Lys Glu Asp Gln Asp Lys Ala Thr Lys Asp Glu Ser Asp 385 390 395 400 Asn Asp Gln Asn Asn Ala Asn Gln Ala Asn Asn Gln Ala Gln Asn Asn 405 410 415 Gln Asn Gln Gln Gln Ala Asn Gln Asn Gln Gln Gln Gln Gln Gln Arg 420 425 430 Gln Gly Gly Gly Gln Arg His Thr Val Asn Gly Gln Glu Asn Leu Tyr 435 440 445 Arg Ile Ala Ile Gln Tyr Tyr Gly Ser Gly Ser Pro Glu Asn Val Glu 450 455 460 Lys Ile Arg Arg Ala Asn Gly Leu Ser Gly Asn Asn Ile Arg Asn Gly 465 470 475 480 Gln Gln Ile Val Ile Pro 485 23 472 PRT S. epidermidis 23 Met Ile Glu Leu Ile Lys Met Glu Gly Met Ile Val Val Ser Asn Asn 1 5 10 15 Asn Phe Lys Asp Asp Phe Glu Lys Asn Arg Gln Ser Ile Asn Pro Asp 20 25 30 Glu Gln Gln Thr Glu Leu Lys Glu Asp Asp Lys Thr Asn Glu Asn Lys 35 40 45 Lys Glu Ala Asp Ser Gln Asn Ser Leu Ser Asn Asn Ser Asn Gln Gln 50 55 60 Phe Pro Pro Arg Asn Ala Gln Arg Arg Lys Arg Arg Arg Glu Thr Ala 65 70 75 80 Thr Asn Gln Ser Lys Gln Gln Asp Asp Lys His Gln Lys Asn Ser Asp 85 90 95 Ala Lys Thr Thr Glu Gly Ser Leu Asp Asp Arg Tyr Asp Glu Ala Gln 100 105 110 Leu Gln Gln Gln His Asp Lys Ser Gln Gln Gln Asn Lys Thr Glu Lys 115 120 125 Gln Ser Gln Asp Asn Arg Met Lys Asp Gly Lys Asp Ala Ala Ile Val 130 135 140 Asn Gly Thr Ser Glu Ser Pro Glu His Lys Ser Lys Ser Thr Gln Asn 145 150 155 160 Arg Pro Gly Pro Lys Ala Gln Gln Gln Lys Arg Lys Ser Glu Ser Thr 165 170 175 Gln Ser Lys Pro Ser Thr Asn Lys Asp Lys Lys Ala Ala Thr Gly Ala 180 185 190 Gly Ile Ala Gly Ala Ala Gly Val Ala Gly Ala Ala Glu Thr Ser Lys 195 200 205 Arg His His Asn Lys Lys Asp Lys Gln Asp Ser Lys His Ser Asn His 210 215 220 Glu Asn Asp Glu Lys Ser Val Lys Asn Asp Asp Gln Lys Gln Ser Lys 225 230 235 240 Lys Gly Lys Lys Ala Ala Val Gly Ala Gly Ala Ala Ala Gly Val Gly 245 250 255 Ala Ala Gly Val Ala His His Asn Asn Gln Asn Lys His His Asn Glu 260 265 270 Glu Lys Asn Ser Asn Gln Asn Asn Gln Tyr Asn Asp Gln Ser Glu Gly 275 280 285 Lys Lys Lys Gly Gly Phe Met Lys Ile Leu Leu Pro Leu Ile Ala Ala 290 295 300 Ile Leu Ile Leu Gly Ala Ile Ala Ile Phe Gly Gly Met Ala Leu Asn 305 310 315 320 Asn His Asn Asp Ser Lys Ser Asp Asp Gln Lys Ile Ala Asn Gln Ser 325 330 335 Lys Lys Asp Ser Asp Lys Lys Asp Gly Ala Gln Ser Glu Asp Asn Lys 340 345 350 Asp Lys Lys Ser Asp Ser Asn Lys Asp Lys Lys Ser Asp Ser Asp Lys 355 360 365 Asn Ala Asp Asp Asp Ser Asp Asn Ser Ser Ser Asn Pro Asn Ala Thr 370 375 380 Ser Thr Asn Asn Asn Asp Asn Val Ala Asn Asn Asn Ser Asn Tyr Thr 385 390 395 400 Asn Gln Asn Gln Gln Asp Asn Ala Asn Gln Asn Ser Asn Asn Gln Gln 405 410 415 Ala Thr Gln Gly Gln Gln Ser His Thr Val Tyr Gly Gln Glu Asn Leu 420 425 430 Tyr Arg Ile Ala Ile Gln Tyr Tyr Gly Glu Gly Thr Gln Ala Asn Val 435 440 445 Asp Lys Ile Lys Arg Ala Asn Gly Leu Ser Ser Asn Asn Ile His Asn 450 455 460 Gly Gln Thr Leu Val Ile Pro Gln 465 470 24 165 PRT S. aureus 24 Met Lys Asn Lys Leu Ile Ala Lys Ser Leu Leu Thr Ile Ala Ala Ile 1 5 10 15 Gly Ile Thr Thr Thr Thr Ile Ala Ser Thr Ala Asp Ala Ser Glu Gly 20 25 30 Tyr Gly Pro Arg Glu Lys Lys Pro Val Ser Ile Asn His Asn Ile Val 35 40 45 Glu Tyr Asn Asp Gly Thr Phe Lys Tyr Gln Ser Arg Pro Lys Phe Asn 50 55 60 Ser Thr Pro Lys Tyr Ile Lys Phe Lys His Asp Tyr Asn Ile Leu Glu 65 70 75 80 Phe Asn Asp Gly Thr Phe Glu Tyr Gly Ala Arg Pro Gln Phe Asn Lys 85 90 95 Pro Ala Ala Lys Thr Asp Ala Thr Ile Lys Lys Glu Gln Lys Leu Ile 100 105 110 Gln Ala Gln Asn Leu Val Arg Glu Phe Glu Lys Thr His Thr Val Ser 115 120 125 Ala His Arg Lys Ala Gln Lys Ala Val Asn Leu Val Ser Phe Glu Tyr 130 135 140 Lys Val Lys Lys Met Val Leu Gln Glu Arg Ile Asp Asn Val Leu Lys 145 150 155 160 Gln Gly Leu Val Arg 165 25 319 PRT S. aureus 25 Met Lys Thr Arg Ile Val Ser Ser Val Thr Thr Thr Leu Leu Leu Gly 1 5 10 15 Ser Ile Leu Met Asn Pro Val Ala Asn Ala Ala Asp Ser Asp Ile Asn 20 25 30 Ile Lys Thr Gly Thr Thr Asp Ile Gly Ser Asn Thr Thr Val Lys Thr 35 40 45 Gly Asp Leu Val Thr Tyr Asp Lys Glu Asn Gly Met His Lys Lys Val 50 55 60 Phe Tyr Ser Phe Ile Asp Asp Lys Asn His Asn Lys Lys Leu Leu Val 65 70 75 80 Ile Arg Thr Lys Gly Thr Ile Ala Gly Gln Tyr Arg Val Tyr Ser Glu 85 90 95 Glu Gly Ala Asn Lys Ser Gly Leu Ala Trp Pro Ser Ala Phe Lys Val 100 105 110 Gln Leu Gln Leu Pro Asp Asn Glu Val Ala Gln Ile Ser Asp Tyr Tyr 115 120 125 Pro Arg Asn Ser Ile Asp Thr Lys Glu Tyr Met Ser Thr Leu Thr Tyr 130 135 140 Gly Phe Asn Gly Asn Val Thr Gly Asp Asp Thr Gly Lys Ile Gly Gly 145 150 155 160 Leu Ile Gly Ala Asn Val Ser Ile Gly His Thr Leu Lys Tyr Val Gln 165 170 175 Pro Asp Phe Lys Thr Ile Leu Glu Ser Pro Thr Asp Lys Lys Val Gly 180 185 190 Trp Lys Val Ile Phe Asn Asn Met Val Asn Gln Asn Trp Gly Pro Tyr 195 200 205 Asp Arg Asp Ser Trp Asn Pro Val Tyr Gly Asn Gln Leu Phe Met Lys 210 215 220 Thr Arg Asn Gly Ser Met Lys Ala Ala Glu Asn Phe Leu Asp Pro Asn 225 230 235 240 Lys Ala Ser Ser Leu Leu Ser Ser Gly Phe Ser Pro Asp Phe Ala Thr 245 250 255 Val Ile Thr Met Asp Arg Lys Ala Ser Lys Gln Gln Thr Asn Ile Asp 260 265 270 Val Ile Tyr Glu Arg Val Arg Asp Asp Tyr Gln Leu His Trp Thr Ser 275 280 285 Thr Asn Trp Lys Gly Thr Asn Thr Lys Asp Lys Trp Thr Asp Arg Ser 290 295 300 Ser Glu Arg Tyr Lys Ile Asp Trp Glu Lys Glu Glu Met Thr Asn 305 310 315 26 428 PRT S. aureus 26 Met His Met Lys Asn Lys Tyr Ile Ser Lys Leu Leu Val Gly Ala Ala 1 5 10 15 Thr Ile Thr Leu Ala Thr Met Ile Ser Asn Gly Glu Ala Lys Ala Ser 20 25 30 Glu Asn Thr Gln Gln Thr Ser Thr Lys His Gln Thr Thr Gln Asn Asn 35 40 45 Tyr Val Thr Asp Gln Gln Lys Ala Phe Tyr Gln Val Leu His Leu Lys 50 55 60 Gly Ile Thr Glu Glu Gln Arg Asn Gln Tyr Ile Lys Thr Leu Arg Glu 65 70 75 80 His Pro Glu Arg Ala Gln Glu Val Phe Ser Glu Ser Leu Lys Asp Ser 85 90 95 Lys Asn Pro Asp Arg Arg Val Ala Gln Gln Asn Ala Phe Tyr Asn Val 100 105 110 Leu Lys Asn Asp Asn Leu Thr Glu Gln Glu Lys Asn Asn Tyr Ile Ala 115 120 125 Gln Ile Lys Glu Asn Pro Asp Arg Ser Gln Gln Val Trp Val Glu Ser 130 135 140 Val Gln Ser Ser Lys Ala Lys Glu Arg Gln Asn Ile Glu Asn Ala Asp 145 150 155 160 Lys Ala Ile Lys Asp Phe Gln Asp Asn Lys Ala Pro His Asp Lys Ser 165 170 175 Ala Ala Tyr Glu Ala Asn Ser Lys Leu Pro Lys Asp Leu Arg Asp Lys 180 185 190 Asn Asn Arg Phe Val Glu Lys Val Ser Ile Glu Lys Ala Ile Val Arg 195 200 205 His Asp Glu Arg Val Lys Ser Ala Asn Asp Ala Ile Ser Lys Leu Asn 210 215 220 Glu Lys Asp Ser Ile Glu Asn Arg Arg Leu Ala Gln Arg Glu Val Asn 225 230 235 240 Lys Ala Pro Met Asp Val Lys Glu His Leu Gln Lys Gln Leu Asp Ala 245 250 255 Leu Val Ala Gln Lys Asp Ala Glu Lys Lys Val Ala Pro Lys Val Glu 260 265 270 Ala Pro Gln Ile Gln Ser Pro Gln Ile Glu Lys Pro Lys Ala Glu Ser 275 280 285 Pro Lys Val Glu Val Pro Gln Ser Lys Leu Leu Gly Tyr Tyr Gln Ser 290 295 300 Leu Lys Asp Ser Phe Asn Tyr Gly Tyr Lys Tyr Leu Thr Asp Thr Tyr 305 310 315 320 Lys Ser Tyr Lys Glu Lys Tyr Asp Thr Ala Lys Tyr Tyr Tyr Asn Thr 325 330 335 Tyr Tyr Lys Tyr Lys Gly Ala Ile Asp Gln Thr Val Leu Thr Val Leu 340 345 350 Gly Ser Gly Ser Lys Ser Tyr Ile Gln Pro Leu Lys Val Asp Asp Lys 355 360 365 Asn Gly Tyr Leu Ala Lys Ser Tyr Ala Gln Val Arg

Asn Tyr Val Thr 370 375 380 Glu Ser Ile Asn Thr Gly Lys Val Leu Tyr Thr Phe Tyr Gln Asn Pro 385 390 395 400 Thr Leu Val Lys Thr Ala Ile Lys Ala Gln Glu Thr Ala Ser Ser Ile 405 410 415 Lys Asn Thr Leu Ser Asn Leu Leu Ser Phe Trp Lys 420 425 27 350 PRT S. aureus 27 Met Thr Lys His Tyr Leu Asn Ser Lys Tyr Gln Ser Glu Gln Arg Ser 1 5 10 15 Ser Ala Met Lys Lys Ile Thr Met Gly Thr Ala Ser Ile Ile Leu Gly 20 25 30 Ser Leu Val Tyr Ile Gly Ala Asp Ser Gln Gln Val Asn Ala Ala Thr 35 40 45 Glu Ala Thr Asn Ala Thr Asn Asn Gln Ser Thr Gln Val Ser Gln Ala 50 55 60 Thr Ser Gln Pro Ile Asn Phe Gln Val Gln Lys Asp Gly Ser Ser Glu 65 70 75 80 Lys Ser His Met Asp Asp Tyr Met Gln His Pro Gly Lys Val Ile Lys 85 90 95 Gln Asn Asn Lys Tyr Tyr Phe Gln Thr Val Leu Asn Asn Ala Ser Phe 100 105 110 Trp Lys Glu Tyr Lys Phe Tyr Asn Ala Asn Asn Gln Glu Leu Ala Thr 115 120 125 Thr Val Val Asn Asp Asn Lys Lys Ala Asp Thr Arg Thr Ile Asn Val 130 135 140 Ala Val Glu Pro Gly Tyr Lys Ser Leu Thr Thr Lys Val His Ile Val 145 150 155 160 Val Pro Gln Ile Asn Tyr Asn His Arg Tyr Thr Thr His Leu Glu Phe 165 170 175 Glu Lys Ala Ile Pro Thr Leu Ala Asp Ala Ala Lys Pro Asn Asn Val 180 185 190 Lys Pro Val Gln Pro Lys Pro Ala Gln Pro Lys Thr Pro Thr Glu Gln 195 200 205 Thr Lys Pro Val Gln Pro Lys Val Glu Lys Val Lys Pro Thr Val Thr 210 215 220 Thr Thr Ser Lys Val Glu Asp Asn His Ser Thr Lys Val Val Ser Thr 225 230 235 240 Asp Thr Thr Lys Asp Gln Thr Lys Thr Gln Thr Ala His Thr Val Lys 245 250 255 Thr Ala Gln Thr Ala Gln Glu Gln Asn Lys Val Gln Thr Pro Val Lys 260 265 270 Asp Val Ala Thr Ala Lys Ser Glu Ser Asn Asn Gln Ala Val Ser Asp 275 280 285 Asn Lys Ser Gln Gln Thr Asn Lys Val Thr Lys His Asn Glu Thr Pro 290 295 300 Lys Gln Ala Ser Lys Ala Lys Glu Leu Pro Lys Thr Gly Leu Thr Ser 305 310 315 320 Val Asp Asn Phe Ile Ser Thr Val Ala Phe Ala Thr Leu Ala Leu Leu 325 330 335 Gly Ser Leu Ser Leu Leu Leu Phe Lys Arg Lys Glu Ser Lys 340 345 350 28 645 PRT S. aureus 28 Met Asn Lys Gln Gln Lys Glu Phe Lys Ser Phe Tyr Ser Ile Arg Lys 1 5 10 15 Ser Ser Leu Gly Val Ala Ser Val Ala Ile Ser Thr Leu Leu Leu Leu 20 25 30 Met Ser Asn Gly Glu Ala Gln Ala Ala Ala Glu Glu Thr Gly Gly Thr 35 40 45 Asn Thr Glu Ala Gln Pro Lys Thr Glu Ala Val Ala Ser Pro Thr Thr 50 55 60 Thr Ser Glu Lys Ala Pro Glu Thr Lys Pro Val Ala Asn Ala Val Ser 65 70 75 80 Val Ser Asn Lys Glu Val Glu Ala Pro Thr Ser Glu Thr Lys Glu Ala 85 90 95 Lys Glu Val Lys Glu Val Lys Ala Pro Lys Glu Thr Lys Ala Val Lys 100 105 110 Pro Ala Ala Lys Ala Thr Asn Asn Thr Tyr Pro Ile Leu Asn Gln Glu 115 120 125 Leu Arg Glu Ala Ile Lys Asn Pro Ala Ile Lys Asp Lys Asp His Ser 130 135 140 Ala Pro Asn Ser Arg Pro Ile Asp Phe Glu Met Lys Lys Glu Asn Gly 145 150 155 160 Glu Gln Gln Phe Tyr His Tyr Ala Ser Ser Val Lys Pro Ala Arg Val 165 170 175 Ile Phe Thr Asp Ser Lys Pro Glu Ile Glu Leu Gly Leu Gln Ser Gly 180 185 190 Gln Phe Trp Arg Lys Phe Glu Val Tyr Glu Gly Asp Lys Lys Leu Pro 195 200 205 Ile Lys Leu Val Ser Tyr Asp Thr Val Lys Asp Tyr Ala Tyr Ile Arg 210 215 220 Phe Ser Val Ser Asn Gly Thr Lys Ala Val Lys Ile Val Ser Ser Thr 225 230 235 240 His Phe Asn Asn Lys Glu Glu Lys Tyr Asp Tyr Thr Leu Met Glu Phe 245 250 255 Ala Gln Pro Ile Tyr Asn Ser Ala Asp Lys Phe Lys Thr Glu Glu Asp 260 265 270 Tyr Lys Ala Glu Lys Leu Leu Ala Pro Tyr Lys Lys Ala Lys Thr Leu 275 280 285 Glu Arg Gln Val Tyr Glu Leu Asn Lys Ile Gln Asp Lys Leu Pro Glu 290 295 300 Lys Leu Lys Ala Glu Tyr Lys Lys Lys Leu Glu Asp Thr Lys Lys Ala 305 310 315 320 Leu Asp Glu Gln Val Lys Ser Ala Ile Thr Glu Phe Gln Asn Val Gln 325 330 335 Pro Thr Asn Glu Lys Met Thr Asp Leu Gln Asp Thr Lys Tyr Val Val 340 345 350 Tyr Glu Ser Val Glu Asn Asn Glu Ser Met Met Asp Thr Phe Val Lys 355 360 365 His Pro Ile Lys Thr Gly Met Leu Asn Gly Lys Lys Tyr Met Val Met 370 375 380 Glu Thr Thr Asn Asp Asp Tyr Trp Lys Asp Phe Met Val Glu Gly Gln 385 390 395 400 Arg Val Arg Thr Ile Ser Lys Asp Ala Lys Asn Asn Thr Arg Thr Ile 405 410 415 Ile Phe Pro Tyr Val Glu Gly Lys Thr Leu Tyr Asp Ala Ile Val Lys 420 425 430 Val His Val Lys Thr Ile Asp Tyr Asp Gly Gln Tyr His Val Arg Ile 435 440 445 Val Asp Lys Glu Ala Phe Thr Lys Ala Asn Thr Asp Lys Ser Asn Lys 450 455 460 Lys Glu Gln Gln Asp Asn Ser Ala Lys Lys Glu Ala Thr Pro Ala Thr 465 470 475 480 Pro Ser Lys Pro Thr Pro Ser Pro Val Glu Lys Glu Ser Gln Lys Gln 485 490 495 Asp Ser Gln Lys Asp Asp Asn Lys Gln Leu Pro Ser Val Glu Lys Glu 500 505 510 Asn Asp Ala Ser Ser Glu Ser Gly Lys Asp Lys Thr Pro Ala Thr Lys 515 520 525 Pro Thr Lys Gly Glu Val Glu Ser Ser Ser Thr Thr Pro Thr Lys Val 530 535 540 Val Ser Thr Thr Gln Asn Val Ala Lys Pro Thr Thr Ala Ser Ser Lys 545 550 555 560 Thr Thr Lys Asp Val Val Gln Thr Ser Ala Gly Ser Ser Glu Ala Lys 565 570 575 Asp Ser Ala Pro Leu Gln Lys Ala Asn Ile Lys Asn Thr Asn Asp Gly 580 585 590 His Thr Gln Ser Gln Asn Asn Lys Asn Thr Gln Glu Asn Lys Ala Lys 595 600 605 Ser Leu Pro Gln Thr Gly Glu Glu Ser Asn Lys Asp Met Thr Leu Pro 610 615 620 Leu Met Ala Leu Leu Ala Leu Ser Ser Ile Val Ala Phe Val Leu Pro 625 630 635 640 Arg Lys Arg Lys Asn 645 29 953 PRT S. aureus 29 Met Asn Asn Lys Lys Thr Ala Thr Asn Arg Lys Gly Met Ile Pro Asn 1 5 10 15 Arg Leu Asn Lys Phe Ser Ile Arg Lys Tyr Ser Val Gly Thr Ala Ser 20 25 30 Ile Leu Val Gly Thr Thr Leu Ile Phe Gly Leu Ser Gly His Glu Ala 35 40 45 Lys Ala Ala Glu His Thr Asn Gly Glu Leu Asn Gln Ser Lys Asn Glu 50 55 60 Thr Thr Ala Pro Ser Glu Asn Lys Thr Thr Glu Lys Val Asp Ser Arg 65 70 75 80 Gln Leu Lys Asp Asn Thr Gln Thr Ala Thr Ala Asp Gln Pro Lys Val 85 90 95 Thr Met Ser Asp Ser Ala Thr Val Lys Glu Thr Ser Ser Asn Met Gln 100 105 110 Ser Pro Gln Asn Ala Thr Ala Ser Gln Ser Thr Thr Gln Thr Ser Asn 115 120 125 Val Thr Thr Asn Asp Lys Ser Ser Thr Thr Tyr Ser Asn Glu Thr Asp 130 135 140 Lys Ser Asn Leu Thr Gln Ala Lys Asn Val Ser Thr Thr Pro Lys Thr 145 150 155 160 Thr Thr Ile Lys Gln Arg Ala Leu Asn Arg Met Ala Val Asn Thr Val 165 170 175 Ala Ala Pro Gln Gln Gly Thr Asn Val Asn Asp Lys Val His Phe Thr 180 185 190 Asn Ile Asp Ile Ala Ile Asp Lys Gly His Val Asn Lys Thr Thr Gly 195 200 205 Asn Thr Glu Phe Trp Ala Thr Ser Ser Asp Val Leu Lys Leu Lys Ala 210 215 220 Asn Tyr Thr Ile Asp Asp Ser Val Lys Glu Gly Asp Thr Phe Thr Phe 225 230 235 240 Lys Tyr Gly Gln Tyr Phe Arg Pro Gly Ser Val Arg Leu Pro Ser Gln 245 250 255 Thr Gln Asn Leu Tyr Asn Ala Gln Gly Asn Ile Ile Ala Lys Gly Ile 260 265 270 Tyr Asp Ser Lys Thr Asn Thr Thr Thr Tyr Thr Phe Thr Asn Tyr Val 275 280 285 Asp Gln Tyr Thr Asn Val Ser Gly Ser Phe Glu Gln Val Ala Phe Ala 290 295 300 Lys Arg Glu Asn Ala Thr Thr Asp Lys Thr Ala Tyr Lys Met Glu Val 305 310 315 320 Thr Leu Gly Asn Asp Thr Tyr Ser Lys Asp Val Ile Val Asp Tyr Gly 325 330 335 Asn Gln Lys Gly Gln Gln Leu Ile Ser Ser Thr Asn Tyr Ile Asn Asn 340 345 350 Glu Asp Leu Ser Arg Asn Met Thr Val Tyr Val Asn Gln Pro Lys Lys 355 360 365 Thr Tyr Thr Lys Glu Thr Phe Val Thr Asn Leu Thr Gly Tyr Lys Phe 370 375 380 Asn Pro Asp Ala Lys Asn Phe Lys Ile Tyr Glu Val Thr Asp Gln Asn 385 390 395 400 Gln Phe Val Asp Ser Phe Thr Pro Asp Thr Ser Lys Leu Lys Asp Val 405 410 415 Thr Gly Gln Phe Asp Val Ile Tyr Ser Asn Asp Asn Lys Thr Ala Thr 420 425 430 Val Asp Leu Leu Asn Gly Gln Ser Ser Ser Asp Lys Gln Tyr Ile Ile 435 440 445 Gln Gln Val Ala Tyr Pro Asp Asn Ser Ser Thr Asp Asn Gly Lys Ile 450 455 460 Asp Tyr Thr Leu Glu Thr Gln Asn Gly Lys Ser Ser Trp Ser Asn Ser 465 470 475 480 Tyr Ser Asn Val Asn Gly Ser Ser Thr Ala Asn Gly Asp Gln Lys Lys 485 490 495 Tyr Asn Leu Gly Asp Tyr Val Trp Glu Asp Thr Asn Lys Asp Gly Lys 500 505 510 Gln Asp Ala Asn Glu Lys Gly Ile Lys Gly Val Tyr Val Ile Leu Lys 515 520 525 Asp Ser Asn Gly Lys Glu Leu Asp Arg Thr Thr Thr Asp Glu Asn Gly 530 535 540 Lys Tyr Gln Phe Thr Gly Leu Ser Asn Gly Thr Tyr Ser Val Glu Phe 545 550 555 560 Ser Thr Pro Ala Gly Tyr Thr Pro Thr Thr Ala Asn Ala Gly Thr Asp 565 570 575 Asp Ala Val Asp Ser Asp Gly Leu Thr Thr Thr Gly Val Ile Lys Asp 580 585 590 Ala Asp Asn Met Thr Leu Asp Ser Gly Phe Tyr Lys Thr Pro Lys Tyr 595 600 605 Ser Leu Gly Asp Tyr Val Trp Tyr Asp Ser Asn Lys Asp Gly Lys Gln 610 615 620 Asp Ser Thr Glu Lys Gly Ile Lys Gly Val Lys Val Thr Leu Gln Asn 625 630 635 640 Glu Lys Gly Glu Val Ile Gly Thr Thr Glu Thr Asp Glu Asn Gly Lys 645 650 655 Tyr Arg Phe Asp Asn Leu Asp Ser Gly Lys Tyr Lys Val Ile Phe Glu 660 665 670 Lys Pro Ala Gly Leu Thr Gln Thr Gly Thr Asn Thr Thr Glu Asp Asp 675 680 685 Lys Asp Ala Asp Gly Gly Glu Val Asp Val Thr Ile Thr Asp His Asp 690 695 700 Asp Phe Thr Leu Asp Asn Gly Tyr Tyr Glu Glu Glu Thr Ser Asp Ser 705 710 715 720 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 725 730 735 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 740 745 750 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 755 760 765 Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 770 775 780 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 785 790 795 800 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 805 810 815 Asp Ser Asp Ser Asp Ser Asp Asn Asp Ser Asp Ser Asp Ser Asp Ser 820 825 830 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 835 840 845 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 850 855 860 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 865 870 875 880 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ala Gly Lys 885 890 895 His Thr Pro Thr Lys Pro Met Ser Thr Val Lys Asp Gln His Lys Thr 900 905 910 Ala Lys Ala Leu Pro Glu Thr Gly Ser Glu Asn Asn Asn Ser Asn Asn 915 920 925 Gly Thr Leu Phe Gly Gly Leu Phe Ala Ala Leu Gly Ser Leu Leu Leu 930 935 940 Phe Gly Arg Arg Lys Lys Gln Asn Lys 945 950 30 935 PRT S. aureus 30 Met Asn Met Lys Lys Lys Glu Lys His Ala Ile Arg Lys Lys Ser Ile 1 5 10 15 Gly Val Ala Ser Val Leu Val Gly Thr Leu Ile Gly Phe Gly Leu Leu 20 25 30 Ser Ser Lys Glu Ala Asp Ala Ser Glu Asn Ser Val Thr Gln Ser Asp 35 40 45 Ser Ala Ser Asn Glu Ser Lys Ser Asn Asp Ser Ser Ser Val Ser Ala 50 55 60 Ala Pro Lys Thr Asp Asp Thr Asn Val Ser Asp Thr Lys Thr Ser Ser 65 70 75 80 Asn Thr Asn Asn Gly Glu Thr Ser Val Ala Gln Asn Pro Ala Gln Gln 85 90 95 Glu Thr Thr Gln Ser Ser Ser Thr Asn Ala Thr Thr Glu Glu Thr Pro 100 105 110 Val Thr Gly Glu Ala Thr Thr Thr Thr Thr Asn Gln Ala Asn Thr Pro 115 120 125 Ala Thr Thr Gln Ser Ser Asn Thr Asn Ala Glu Glu Leu Val Asn Gln 130 135 140 Thr Ser Asn Glu Thr Thr Ser Asn Asp Thr Asn Thr Val Ser Ser Val 145 150 155 160 Asn Ser Pro Gln Asn Ser Thr Asn Ala Glu Asn Val Ser Thr Thr Gln 165 170 175 Asp Thr Ser Thr Glu Ala Thr Pro Ser Asn Asn Glu Ser Ala Pro Gln 180 185 190 Asn Thr Asp Ala Ser Asn Lys Asp Val Val Ser Gln Ala Val Asn Pro 195 200 205 Ser Thr Pro Arg Met Arg Ala Phe Ser Leu Ala Ala Val Ala Ala Asp 210 215 220 Ala Pro Ala Ala Gly Thr Asp Ile Thr Asn Gln Leu Thr Asp Val Lys 225 230 235 240 Val Thr Ile Asp Ser Gly Thr Thr Val Tyr Pro His Gln Ala Gly Tyr 245 250 255 Val Lys Leu Asn Tyr Gly Phe Ser Val Pro Asn Ser Ala Val Lys Gly 260 265 270 Asp Thr Phe Lys Ile Thr Val Pro Lys Glu Leu Asn Leu Asn Gly Val 275 280 285 Thr Ser Thr Ala Lys Val Pro Pro Ile Met Ala Gly Asp Gln Val Leu 290 295 300 Ala Asn Gly Val Ile Asp Ser Asp Gly Asn Val Ile Tyr Thr Phe Thr 305 310 315 320 Asp Tyr Val Asp Asn Lys Glu Asn Val Thr Ala Asn Ile Thr Met Pro 325 330 335 Ala Tyr Ile Asp Pro Glu Asn Val Thr Lys Thr Gly Asn Val Thr Leu 340 345 350 Thr Thr Gly Ile Gly Thr Asn Thr Ala Ser Lys Thr Val Leu Ile Asp 355 360 365 Tyr Glu Lys Tyr Gly Gln Phe His Asn Leu Ser Ile Lys Gly Thr Ile 370 375 380 Asp Gln Ile Asp Lys Thr Asn Asn Thr Tyr Arg Gln Thr Ile Tyr Val 385 390 395 400 Asn Pro Ser Gly Asp Asn Val Val Leu Pro Ala Leu Thr Gly Asn Leu 405 410 415 Ile Pro Asn Thr Lys Ser Asn Ala Leu Ile Asp Ala Lys Asn Thr Asp 420 425 430 Ile Lys Val Tyr Arg Val Asp Asn Ala Asn Asp Leu Ser Glu

Ser Tyr 435 440 445 Tyr Val Asn Pro Ser Asp Phe Glu Asp Val Thr Asn Gln Val Arg Ile 450 455 460 Ser Phe Pro Asn Ala Asn Gln Tyr Lys Val Glu Phe Pro Thr Asp Asp 465 470 475 480 Asp Gln Ile Thr Thr Pro Tyr Ile Val Val Val Asn Gly His Ile Asp 485 490 495 Pro Ala Ser Thr Gly Asp Leu Ala Leu Arg Ser Thr Phe Tyr Gly Tyr 500 505 510 Asp Ser Asn Phe Ile Trp Arg Ser Met Ser Trp Asp Asn Glu Val Ala 515 520 525 Phe Asn Asn Gly Ser Gly Ser Gly Asp Gly Ile Asp Lys Pro Val Val 530 535 540 Pro Glu Gln Pro Asp Glu Pro Gly Glu Ile Glu Pro Ile Pro Glu Asp 545 550 555 560 Ser Asp Ser Asp Pro Gly Ser Asp Ser Gly Ser Asp Ser Asn Ser Asp 565 570 575 Ser Gly Ser Asp Ser Gly Ser Asp Ser Thr Ser Asp Ser Gly Ser Asp 580 585 590 Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp 595 600 605 Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala 610 615 620 Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp 625 630 635 640 Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp 645 650 655 Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Asp 660 665 670 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 675 680 685 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 690 695 700 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 705 710 715 720 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 725 730 735 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 740 745 750 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Ala 755 760 765 Ser Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp 770 775 780 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 785 790 795 800 Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser Asp 805 810 815 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp 820 825 830 Ser Gly Ser Asp Ser Asp Ser Ser Ser Asp Ser Asp Ser Asp Ser Thr 835 840 845 Ser Asp Thr Gly Ser Asp Asn Asp Ser Asp Ser Asp Ser Asn Ser Asp 850 855 860 Ser Glu Ser Gly Ser Asn Asn Asn Val Val Pro Pro Asn Ser Pro Lys 865 870 875 880 Asn Gly Thr Asn Ala Ser Asn Lys Asn Glu Ala Lys Asp Ser Lys Glu 885 890 895 Pro Leu Pro Asp Thr Gly Ser Glu Asp Glu Ala Asn Thr Ser Leu Ile 900 905 910 Trp Gly Leu Leu Ala Ser Leu Gly Ser Leu Leu Leu Phe Arg Arg Lys 915 920 925 Lys Glu Asn Lys Asp Lys Lys 930 935 31 1038 PRT S. aureus 31 Met Lys Asn Asn Leu Arg Tyr Gly Ile Arg Lys His Lys Leu Gly Ala 1 5 10 15 Ala Ser Val Phe Leu Gly Thr Met Ile Val Val Gly Met Gly Gln Asp 20 25 30 Lys Glu Ala Ala Ala Ser Glu Gln Lys Thr Thr Thr Val Glu Glu Asn 35 40 45 Gly Asn Ser Ala Thr Asp Asn Lys Thr Ser Glu Thr Gln Thr Thr Ala 50 55 60 Thr Asn Val Asn His Ile Glu Glu Thr Gln Ser Tyr Asn Ala Thr Val 65 70 75 80 Thr Glu Gln Pro Ser Asn Ala Thr Gln Val Thr Thr Glu Glu Ala Pro 85 90 95 Lys Ala Val Gln Ala Pro Gln Thr Ala Gln Pro Ala Asn Val Glu Thr 100 105 110 Val Lys Glu Glu Glu Lys Pro Gln Val Lys Glu Thr Thr Gln Pro Gln 115 120 125 Asp Asn Ser Gly Asn Gln Arg Gln Val Asp Leu Thr Pro Lys Lys Val 130 135 140 Thr Gln Asn Gln Gly Thr Glu Thr Gln Val Glu Val Ala Gln Pro Arg 145 150 155 160 Thr Ala Ser Glu Ser Lys Pro Arg Val Thr Arg Ser Ala Asp Val Ala 165 170 175 Glu Ala Lys Glu Ala Ser Asp Val Ser Glu Val Lys Gly Thr Asp Val 180 185 190 Thr Ser Lys Val Thr Val Glu Ser Gly Ser Ile Glu Ala Pro Gln Gly 195 200 205 Asn Lys Val Glu Pro His Ala Gly Gln Arg Val Val Leu Lys Tyr Lys 210 215 220 Leu Lys Phe Ala Asp Gly Leu Lys Arg Gly Asp Tyr Phe Asp Phe Thr 225 230 235 240 Leu Ser Asn Asn Val Asn Thr Tyr Gly Val Ser Thr Ala Arg Lys Val 245 250 255 Pro Glu Ile Lys Asn Gly Ser Val Val Met Ala Thr Gly Glu Ile Leu 260 265 270 Gly Asn Gly Asn Ile Arg Tyr Thr Phe Thr Asn Glu Ile Glu His Lys 275 280 285 Val Glu Val Thr Ala Asn Leu Glu Ile Asn Leu Phe Ile Asp Pro Lys 290 295 300 Thr Val Gln Ser Asn Gly Glu Gln Lys Ile Thr Ser Lys Leu Asn Gly 305 310 315 320 Glu Glu Thr Glu Lys Thr Ile Pro Val Val Tyr Asn Pro Gly Val Ser 325 330 335 Asn Ser Tyr Thr Asn Val Asn Gly Ser Ile Glu Thr Phe Asn Lys Glu 340 345 350 Ser Asn Lys Phe Thr His Ile Ala Tyr Ile Lys Pro Met Asn Gly Asn 355 360 365 Gln Ser Asn Thr Val Ser Val Thr Gly Thr Leu Thr Glu Gly Ser Asn 370 375 380 Leu Ala Gly Gly Gln Pro Thr Val Lys Val Tyr Glu Tyr Leu Gly Lys 385 390 395 400 Lys Asp Glu Leu Pro Gln Ser Val Tyr Ala Asn Thr Ser Asp Thr Asn 405 410 415 Lys Phe Lys Asp Val Thr Lys Glu Met Asn Gly Lys Leu Ser Val Gln 420 425 430 Asp Asn Gly Ser Tyr Ser Leu Asn Leu Asp Lys Leu Asp Lys Thr Tyr 435 440 445 Val Ile His Tyr Thr Gly Glu Tyr Leu Gln Gly Ser Asp Gln Val Asn 450 455 460 Phe Arg Thr Glu Leu Tyr Gly Tyr Pro Glu Arg Ala Tyr Lys Ser Tyr 465 470 475 480 Tyr Val Tyr Gly Gly Tyr Arg Leu Thr Trp Asp Asn Gly Leu Val Leu 485 490 495 Tyr Ser Asn Lys Ala Asp Gly Asn Gly Lys Asn Gly Gln Ile Ile Gln 500 505 510 Asp Asn Asp Phe Glu Tyr Lys Glu Asp Thr Ala Lys Gly Thr Met Ser 515 520 525 Gly Gln Tyr Asp Ala Lys Gln Ile Ile Glu Thr Glu Glu Asn Gln Asp 530 535 540 Asn Thr Pro Leu Asp Ile Asp Tyr His Thr Ala Ile Asp Gly Glu Gly 545 550 555 560 Gly Tyr Val Asp Gly Tyr Ile Glu Thr Ile Glu Glu Thr Asp Ser Ser 565 570 575 Ala Ile Asp Ile Asp Tyr His Thr Ala Val Asp Ser Glu Val Gly His 580 585 590 Val Gly Gly Tyr Thr Glu Ser Ser Glu Glu Ser Asn Pro Ile Asp Phe 595 600 605 Glu Glu Ser Thr His Glu Asn Ser Lys His His Ala Asp Val Val Glu 610 615 620 Tyr Glu Glu Asp Thr Asn Pro Gly Gly Gly Gln Val Thr Thr Glu Ser 625 630 635 640 Asn Leu Val Glu Phe Asp Glu Glu Ser Thr Lys Gly Ile Val Thr Gly 645 650 655 Ala Val Ser Asp His Thr Thr Ile Glu Asp Thr Lys Glu Tyr Thr Thr 660 665 670 Glu Ser Asn Leu Ile Glu Leu Val Asp Glu Leu Pro Glu Glu His Gly 675 680 685 Gln Ala Gln Gly Pro Ile Glu Glu Ile Thr Glu Asn Asn His His Ile 690 695 700 Ser His Ser Gly Leu Gly Thr Glu Asn Gly His Gly Asn Tyr Gly Val 705 710 715 720 Ile Glu Glu Ile Glu Glu Asn Ser His Val Asp Ile Lys Ser Glu Leu 725 730 735 Gly Tyr Glu Gly Gly Gln Asn Ser Gly Asn Gln Ser Phe Glu Glu Asp 740 745 750 Thr Glu Glu Asp Lys Pro Lys Tyr Glu Gln Gly Gly Asn Ile Val Asp 755 760 765 Ile Asp Phe Asp Ser Val Pro Gln Ile His Gly Gln Asn Lys Gly Asp 770 775 780 Gln Ser Phe Glu Glu Asp Thr Glu Lys Asp Lys Pro Lys Tyr Glu His 785 790 795 800 Gly Gly Asn Ile Ile Asp Ile Asp Phe Asp Ser Val Pro Gln Ile His 805 810 815 Gly Phe Asn Lys His Asn Glu Ile Ile Glu Glu Asp Thr Asn Lys Asp 820 825 830 Lys Pro Asn Tyr Gln Phe Gly Gly His Asn Ser Val Asp Phe Glu Glu 835 840 845 Asp Thr Leu Pro Lys Val Ser Gly Gln Asn Glu Gly Gln Gln Thr Ile 850 855 860 Glu Glu Asp Thr Thr Pro Pro Thr Pro Pro Thr Pro Glu Val Pro Ser 865 870 875 880 Glu Pro Glu Thr Pro Met Pro Pro Thr Pro Glu Val Pro Ser Glu Pro 885 890 895 Glu Thr Pro Thr Pro Pro Thr Pro Glu Val Pro Ser Glu Pro Glu Thr 900 905 910 Pro Thr Pro Pro Thr Pro Glu Val Pro Ser Glu Pro Glu Thr Pro Thr 915 920 925 Pro Pro Thr Pro Glu Val Pro Ser Glu Pro Glu Thr Pro Thr Pro Pro 930 935 940 Thr Pro Glu Val Pro Ala Glu Pro Gly Lys Pro Val Pro Pro Ala Lys 945 950 955 960 Glu Glu Pro Lys Lys Pro Ser Lys Pro Val Glu Gln Gly Lys Val Val 965 970 975 Thr Pro Val Ile Glu Ile Asn Glu Lys Val Lys Ala Val Ala Pro Thr 980 985 990 Lys Lys Ala Gln Ser Lys Lys Ser Glu Leu Pro Glu Thr Gly Gly Glu 995 1000 1005 Glu Ser Thr Asn Lys Gly Met Leu Phe Gly Gly Leu Phe Ser Ile Leu 1010 1015 1020 Gly Leu Ala Leu Leu Arg Arg Asn Lys Lys Asn Asn Lys Ala 1025 1030 1035 32 877 PRT S. aureus 32 Met Lys Lys Arg Ile Asp Tyr Leu Ser Asn Lys Gln Asn Lys Tyr Ser 1 5 10 15 Ile Arg Arg Phe Thr Val Gly Thr Thr Ser Val Ile Val Gly Ala Thr 20 25 30 Ile Leu Phe Gly Ile Gly Asn His Gln Ala Gln Ala Ser Glu Gln Ser 35 40 45 Asn Asp Thr Thr Gln Ser Ser Lys Asn Asn Ala Ser Ala Asp Ser Glu 50 55 60 Lys Asn Asn Met Ile Glu Thr Pro Gln Leu Asn Thr Thr Ala Asn Asp 65 70 75 80 Thr Ser Asp Ile Ser Ala Asn Thr Asn Ser Ala Asn Val Asp Ser Thr 85 90 95 Thr Lys Pro Met Ser Thr Gln Thr Ser Asn Thr Thr Thr Thr Glu Pro 100 105 110 Ala Ser Thr Asn Glu Thr Pro Gln Pro Thr Ala Ile Lys Asn Gln Ala 115 120 125 Thr Ala Ala Lys Met Gln Asp Gln Thr Val Pro Gln Glu Ala Asn Ser 130 135 140 Gln Val Asp Asn Lys Thr Thr Asn Asp Ala Asn Ser Ile Ala Thr Asn 145 150 155 160 Ser Glu Leu Lys Asn Ser Gln Thr Leu Asp Leu Pro Gln Ser Ser Pro 165 170 175 Gln Thr Ile Ser Asn Ala Gln Gly Thr Ser Lys Pro Ser Val Arg Thr 180 185 190 Arg Ala Val Arg Ser Leu Ala Val Ala Glu Pro Val Val Asn Ala Ala 195 200 205 Asp Ala Lys Gly Thr Asn Val Asn Asp Lys Val Thr Ala Ser Asn Phe 210 215 220 Lys Leu Glu Lys Thr Thr Phe Asp Pro Asn Gln Ser Gly Asn Thr Phe 225 230 235 240 Met Ala Ala Asn Phe Thr Val Thr Asp Lys Val Lys Ser Gly Asp Tyr 245 250 255 Phe Thr Ala Lys Leu Pro Asp Ser Leu Thr Gly Asn Gly Asp Val Asp 260 265 270 Tyr Ser Asn Ser Asn Asn Thr Met Pro Ile Ala Asp Ile Lys Ser Thr 275 280 285 Asn Gly Asp Val Val Ala Lys Ala Thr Tyr Asp Ile Leu Thr Lys Thr 290 295 300 Tyr Thr Phe Val Phe Thr Asp Tyr Val Asn Asn Lys Glu Asn Ile Asn 305 310 315 320 Gly Gln Phe Ser Leu Pro Leu Phe Thr Asp Arg Ala Lys Ala Pro Lys 325 330 335 Ser Gly Thr Tyr Asp Ala Asn Ile Asn Ile Ala Asp Glu Met Phe Asn 340 345 350 Asn Lys Ile Thr Tyr Asn Tyr Ser Ser Pro Ile Ala Gly Ile Asp Lys 355 360 365 Pro Asn Gly Ala Asn Ile Ser Ser Gln Ile Ile Gly Val Asp Thr Ala 370 375 380 Ser Gly Gln Asn Thr Tyr Lys Gln Thr Val Phe Val Asn Pro Lys Gln 385 390 395 400 Arg Val Leu Gly Asn Thr Trp Val Tyr Ile Lys Gly Tyr Gln Asp Lys 405 410 415 Ile Glu Glu Ser Ser Gly Lys Val Ser Ala Thr Asp Thr Lys Leu Arg 420 425 430 Ile Phe Glu Val Asn Asp Thr Ser Lys Leu Ser Asp Ser Tyr Tyr Ala 435 440 445 Asp Pro Asn Asp Ser Asn Leu Lys Glu Val Thr Asp Gln Phe Lys Asn 450 455 460 Arg Ile Tyr Tyr Glu His Pro Asn Val Ala Ser Ile Lys Phe Gly Asp 465 470 475 480 Ile Thr Lys Thr Tyr Val Val Leu Val Glu Gly His Tyr Asp Asn Thr 485 490 495 Gly Lys Asn Leu Lys Thr Gln Val Ile Gln Glu Asn Val Asp Pro Val 500 505 510 Thr Asn Arg Asp Tyr Ser Ile Phe Gly Trp Asn Asn Glu Asn Val Val 515 520 525 Arg Tyr Gly Gly Gly Ser Ala Asp Gly Asp Ser Ala Val Asn Pro Lys 530 535 540 Asp Pro Thr Pro Gly Pro Pro Val Asp Pro Glu Pro Ser Pro Asp Pro 545 550 555 560 Glu Pro Glu Pro Thr Pro Asp Pro Glu Pro Ser Pro Asp Pro Glu Pro 565 570 575 Glu Pro Ser Pro Asp Pro Asp Pro Asp Ser Asp Ser Asp Ser Asp Ser 580 585 590 Gly Ser Asp Ser Asp Ser Gly Ser Asp Ser Asp Ser Glu Ser Asp Ser 595 600 605 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser 610 615 620 Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 625 630 635 640 Asp Ser Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser 645 650 655 Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Glu Ser 660 665 670 Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 675 680 685 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 690 695 700 Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser 705 710 715 720 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 725 730 735 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 740 745 750 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 755 760 765 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 770 775 780 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 785 790 795 800 Asp Ser Asp Ser Arg Val Thr Pro Pro Asn Asn Glu Gln Lys Ala Pro 805 810 815 Ser Asn Pro Lys Gly Glu Val Asn His Ser Asn Lys Val Ser Lys Gln 820 825 830 His Lys Thr Asp Ala Leu Pro Glu Thr Gly Asp Lys Ser Glu Asn Thr 835 840 845 Asn Ala Thr Leu Phe Gly Ala Met Met Ala Leu Leu Gly Ser Leu Leu 850 855 860 Leu Phe Arg Lys Arg Lys Gln Asp His Lys Glu Lys Ala 865 870 875 33 658 PRT S. aureus 33 Met Lys Lys Gln Ile Ile Ser Leu Gly Ala Leu Ala Val Ala Ser Ser 1 5 10 15 Leu Phe Thr Trp Asp Asn Lys Ala Asp Ala Ile Val Thr Lys Asp Tyr 20 25

30 Ser Lys Glu Ser Arg Val Asn Glu Lys Ser Lys Lys Gly Ala Thr Val 35 40 45 Ser Asp Tyr Tyr Tyr Trp Lys Ile Ile Asp Ser Leu Glu Ala Gln Phe 50 55 60 Thr Gly Ala Ile Asp Leu Leu Glu Asp Tyr Lys Tyr Gly Asp Pro Ile 65 70 75 80 Tyr Lys Glu Ala Lys Asp Arg Leu Met Thr Arg Val Leu Gly Glu Asp 85 90 95 Gln Tyr Leu Leu Lys Lys Lys Ile Asp Glu Tyr Glu Leu Tyr Lys Lys 100 105 110 Trp Tyr Lys Ser Ser Asn Lys Asn Thr Asn Met Leu Thr Phe His Lys 115 120 125 Tyr Asn Leu Tyr Asn Leu Thr Met Asn Glu Tyr Asn Asp Ile Phe Asn 130 135 140 Ser Leu Lys Asp Ala Val Tyr Gln Phe Asn Lys Glu Val Lys Glu Ile 145 150 155 160 Glu His Lys Asn Val Asp Leu Lys Gln Phe Asp Lys Asp Gly Glu Asp 165 170 175 Lys Ala Thr Lys Glu Val Tyr Asp Leu Val Ser Glu Ile Asp Thr Leu 180 185 190 Val Val Thr Tyr Tyr Ala Asp Lys Asp Tyr Gly Glu His Ala Lys Glu 195 200 205 Leu Arg Ala Lys Leu Asp Leu Ile Leu Gly Asp Thr Asp Asn Pro His 210 215 220 Lys Ile Thr Asn Glu Arg Ile Lys Lys Glu Met Ile Asp Asp Leu Asn 225 230 235 240 Ser Ile Ile Asp Asp Phe Phe Met Glu Thr Lys Gln Asn Arg Pro Asn 245 250 255 Ser Ile Thr Lys Tyr Asp Pro Thr Lys His Asn Phe Lys Glu Lys Ser 260 265 270 Glu Asn Lys Pro Asn Phe Asp Lys Leu Val Glu Glu Thr Lys Lys Ala 275 280 285 Val Lys Glu Ala Asp Glu Ser Trp Lys Asn Lys Thr Val Lys Lys Tyr 290 295 300 Glu Glu Thr Val Thr Lys Ser Pro Val Val Lys Glu Glu Lys Lys Val 305 310 315 320 Glu Glu Pro Gln Leu Pro Lys Val Gly Asn Gln Gln Glu Val Lys Thr 325 330 335 Thr Ala Gly Lys Ala Glu Glu Thr Thr Gln Pro Val Ala Gln Pro Leu 340 345 350 Val Lys Ile Pro Gln Glu Thr Ile Tyr Gly Glu Thr Val Lys Gly Pro 355 360 365 Glu Tyr Pro Thr Met Glu Asn Lys Thr Leu Gln Gly Glu Ile Val Gln 370 375 380 Gly Pro Asp Phe Leu Thr Met Glu Gln Asn Arg Pro Ser Leu Ser Asp 385 390 395 400 Asn Tyr Thr Gln Pro Thr Thr Pro Asn Pro Ile Leu Glu Gly Leu Glu 405 410 415 Gly Ser Ser Ser Lys Leu Glu Ile Lys Pro Gln Gly Thr Glu Ser Thr 420 425 430 Leu Lys Gly Ile Gln Gly Glu Ser Ser Asp Ile Glu Val Lys Pro Gln 435 440 445 Ala Thr Glu Thr Thr Glu Ala Ser Gln Tyr Gly Pro Arg Pro Gln Phe 450 455 460 Asn Lys Thr Pro Lys Tyr Val Lys Tyr Arg Asp Ala Gly Thr Gly Ile 465 470 475 480 Arg Glu Tyr Asn Asp Gly Thr Phe Gly Tyr Glu Ala Arg Pro Arg Phe 485 490 495 Asn Lys Pro Ser Glu Thr Asn Ala Tyr Asn Val Thr Thr Asn Gln Asp 500 505 510 Gly Thr Val Ser Tyr Gly Ala Arg Pro Thr Gln Asn Lys Pro Ser Glu 515 520 525 Thr Asn Ala Tyr Asn Val Thr Thr His Ala Asn Gly Gln Val Ser Tyr 530 535 540 Gly Ala Arg Pro Thr Gln Lys Lys Pro Ser Lys Thr Asn Ala Tyr Asn 545 550 555 560 Val Thr Thr His Ala Asn Gly Gln Val Ser Tyr Gly Ala Arg Pro Thr 565 570 575 Gln Lys Lys Pro Ser Lys Thr Asn Ala Tyr Asn Val Thr Thr His Ala 580 585 590 Asn Gly Gln Val Ser Tyr Gly Ala Arg Pro Thr Tyr Lys Lys Pro Ser 595 600 605 Glu Thr Asn Ala Tyr Asn Val Thr Thr His Ala Asn Gly Gln Val Ser 610 615 620 Tyr Gly Ala Arg Pro Thr Gln Lys Lys Pro Ser Glu Thr Asn Ala Tyr 625 630 635 640 Asn Val Thr Thr His Ala Asp Gly Thr Ala Thr Tyr Gly Pro Arg Val 645 650 655 Thr Lys 34 1602 DNA S. aureus 34 atgttacaag taactgatgt gagtttacgt tttggagatc gtaaactatt tgaagatgta 60 aatattaaat ttacagaagg taattgttat ggattaattg gtgcgaatgg tgcaggtaaa 120 tcaacattct taaaaatatt atctggtgaa ttagattctc aaacaggaca tgtttcatta 180 ggtaaaaatg aacgtctagc tgttttaaaa caggaccact atgcttatga agatgaacgc 240 gtgcttgatg ttgtaattaa aggtcacgaa cgtctttatg aggttatgaa agaaaaagat 300 gaaatctata tgaagccaga tttcagtgat gaagatggta tccgtgctgc tgaacttgaa 360 ggtgaatttg cagaaatgaa tggttggaat gctgaagctg atgctgctaa ccttttatct 420 ggtttaggta tcgatccaac tttacacgat aaaaaaatgg ctgaattaga aaacaaccaa 480 aaaattaaag tattattagc gcaaagttta ttcggtgaac cagacgtact attactggat 540 gagcctacta acggtctcga tattccagca atcagttggt tagaagattt cttaattaac 600 tttgataata ctgttatcgt agtatcgcat gaccgtcatt tcttaaataa tgtatgtact 660 catatcgctg atttagactt cggtaaaatt aaagtttatg ttggtaacta tgatttttgg 720 tatcaatcta gtcagttagc tcaaaagatg gctcaagaac aaaacaagaa aaaagaagaa 780 aaaatgaaag agttacagga ctttattgca cgtttctcag ctaacgcttc taaatctaaa 840 caagcaacaa gtcgtaaaaa acaacttgag aaaattgaat tagatgatat tcaaccatca 900 tcaagaagat atcctttcgt taaattcacg cctgagcgtg agattggtaa cgacttatta 960 atcgttcaaa atctttctaa aacaattgac ggcgaaaaag tattagataa tgtatcattc 1020 acaatgaatc caaatgataa agcgatttta attggagata gtgaaattgc aaaaacaaca 1080 ttacttaaaa tattagctgg cgaaatggaa ccagacgaag gttcatttaa atggggtgtt 1140 actacatcat taagttactt ccctaaagat aactcagagt tctttgaggg tgtaaatatg 1200 aatctcgttg attggttaag acaatatgct cctgaagatg aacaaacaga aacattttta 1260 cgtggtttct taggtcgtat gttatttagt ggtgaagaag ttaagaaaaa agctagtgtg 1320 ctttcaggtg gagaaaaagt acgttgtatg ctaagtaaaa tgatgttatc aagtgcgaat 1380 gtacttttac ttgacgaacc tactaaccac ttagacttag aaagtattac tgctgtcaat 1440 gatggtctta aatcatttaa aggttctatc atctttactt cttatgactt cgaatttatc 1500 aacacgattg caaaccgtgt tatcgattta aataaacaag gcggcgtttc aaaagaaatt 1560 ccatatgaag aatacttgca agaaatcggc gttttaaaat aa 1602 35 1608 DNA S. epidermidis 35 atgttacaag taactgatgt aagtttacgt tttggtgatc gtaaactatt tgaagatgta 60 aatataaaat ttacagaggg taattgttat ggattaattg gtgcaaatgg tgctgggaaa 120 tctacattct tgaagatttt atcaggcgaa attgattcac agactggtca tgtatctcta 180 ggtaaagatg agcgtttggc tgtgttaaaa caagatcatt ttgcttatga agatgaacgt 240 gttttagatg ttgtgattaa aggacatgaa cgtttgtatc aagtgatgaa agagaaagat 300 gaaatttata tgaaacctga tttcagcgat gaggacggta ttcgcgctgc agaacttgaa 360 ggagaatttg cagaaatgaa cggttggaat gctgaagctg atgctgctaa cttattatca 420 ggattaggca tagaacctga cttacatgat aaaaatatgt ctgaacttga aaataatcaa 480 aaagttaagg tattgttagc tcaaagttta tttggtgatc ctgacgttct tttactagat 540 gagcctacca atggtttaga tataccagca ataagttggt tagaagactt tttaattaat 600 tttgaaaata ctgtcattgt cgtttcgcat gaccgtcact tcttaaataa tgtttgtact 660 catattgctg atttagactt tggcaaaatt aaactttatg ttggtaacta tgatttttgg 720 tatcaatcaa gtcaattagc acaaaaaatg gcacaagaac aaaataagaa aaaagaagaa 780 aaaatgaaag agttacagga tttcatcgca cgcttctcag caaatgcttc taaatctaaa 840 caggcaacaa gtcgtaagaa acaattagaa aaaattgaat tagatgatat ccagccatca 900 tctcgtagat acccttacgt gaaatttact cctgaacgtg aaattggaaa tgatttactt 960 acagtagaaa atctttctaa aacaattgac ggcgaaaaag tactagacaa tgtttcattc 1020 actatgaatc ctaatgataa agctatttta gttggtgata gcgaaattgc taaaacaaca 1080 ttgttaaaaa ttttagctgg agaaatggaa ccagatgaag gtacatttaa atggggtgta 1140 acgacatctt taagttactt ccctaaagat aactctgagt tctttgatgg tgtcgatatg 1200 aatttagttg aatggttacg tcaatacgct ccagaagatg aacaaactga aacattttta 1260 cgtggtttct taggtcgcat gttatttagt ggtgaggaag ttaagaaaaa agcaagcgtg 1320 ctttcaggtg gagaaaaagt acgttgcatg ttaagtaaaa tgatgttatc aagtgctaac 1380 gtacttttac ttgatgagcc aacaaaccat ttagatttgg aaagtatcac tgctgtaaat 1440 gacggattaa aatcatttaa aggttctatc atcttcactt cttatgattt tgaatttatt 1500 aatacaatcg caaatcgagt gattgacttg aatcaagctg gtgccctttc taaagaagta 1560 ccttatgagg aatacttaca agaaattggt gtattacaaa ataattaa 1608 36 1305 DNA S. aureus 36 atgccaatta ttacagatgt ttacgctcgc gaagtcttag actctcgtgg taacccaact 60 gttgaagtag aagtattaac tgaaagtggc gcatttggtc gtgcattagt accatcaggt 120 gcttcaactg gtgaacacga agctgttgaa ttacgtgatg gagacaaatc acgttattta 180 ggtaaaggtg ttactaaagc agttgaaaac gttaatgaaa tcatcgcacc agaaattatt 240 gaaggtgaat tttcagtatt agatcaagta tctattgata aaatgatgat cgcattagac 300 ggtactccaa acaaaggtaa attaggtgca aatgctattt taggtgtatc tatcgcagta 360 gcacgtgcag cagctgactt attaggtcaa ccactttaca aatatttagg tggatttaat 420 ggtaagcagt taccagtacc aatgatgaac atcgttaatg gtggttctca ctcagatgct 480 ccaattgcat tccaagaatt catgatttta cctgtaggtg ctacaacgtt caaagaatca 540 ttacgttggg gtactgaaat tttccacaac ttaaaatcaa ttttaagcaa acgtggttta 600 gaaactgcag taggtgacga aggtggtttc gctcctaaat ttgaaggtac tgaagatgct 660 gttgaaacaa ttatccaagc aatcgaagca gctggttaca aaccaggtga agaagtattc 720 ttaggatttg actgtgcatc atcagaattc tatgaaaatg gtgtatatga ctacagtaag 780 ttcgaaggcg aacacggtgc aaaacgtaca gctgcagaac aagttgacta cttagaacaa 840 ttagtagaca aatatcctat cattacaatt gaagacggta tggacgaaaa cgactgggat 900 ggttggaaac aacttacaga acgtatcggt gaccgtgtac aattagtagg tgacgattta 960 ttcgtaacaa acactgaaat tttagcaaaa ggtattgaaa acggaattgg taactcaatc 1020 ttaattaaag ttaaccaaat cggtacatta actgaaacat ttgatgcaat cgaaatggct 1080 caaaaagctg gttacacagc agtagtttct caccgttcag gtgaaacaga agatacaaca 1140 attgctgata ttgctgttgc tacaaacgct ggtcaaatta aaactggttc attatcacgt 1200 actgaccgta ttgctaaata caatcaatta ttacgtatcg aagatgaatt atttgaaact 1260 gctaaatatg acggtatcaa atcattctat aacttagata aataa 1305 37 1305 DNA S. epidermidis 37 atgccaatta ttacagatgt ttacgctcgc gaagtcttag actcacgtgg taacccaaca 60 gttgaagttg aagtattaac tgaaagcggt gctttcggac gtgcattagt accttctggt 120 gcttctactg gtgaacatga agcagttgaa ttacgtgatg gagataaatc acgttattta 180 ggtaaaggtg tgactaaagc ggtagaaaat gttaacgaaa tgatcgcacc agaaatcgtt 240 gaaggtgaat tttcagtttt agatcaagta tctattgata aaatgatgat tcaattagac 300 ggtacacaca acaaaggtaa attaggtgca aatgccattt taggtgtttc tattgccgta 360 gctcgtgcag ctgctgactt attaggtcaa ccattatata aatatttagg tggatttaat 420 ggtaaacaat tgccagtacc tatgatgaat attgttaatg gtggttctca ctcagatgca 480 ccaattgctt tccaagagtt catgatttta cctgtaggtg ctgagtcatt caaagaatca 540 ttacgttggg gtgcagaaat cttccataac cttaaatcaa tcttaagtga acgtggttta 600 gaaactgcag taggtgatga aggtggtttc gctcctagat ttgaaggcac tgaagacgct 660 gtagaaacta ttattaaagc tatcgaaaaa gcaggataca aaccaggtga agatgtattc 720 ttaggatttg actgtgcttc ttctgaattc tatgaaaatg gtgtttatga ttacactaaa 780 ttcgaaggtg aacacggtgc taaacgtagt gcagcagagc aagttgacta cttagaagaa 840 ttaattggta aatatccaat catcactatt gaagatggta tggatgaaaa cgattgggaa 900 ggttggaaac aattaactga tcgtatcggt gataaagttc aattagttgg tgatgattta 960 ttcgtaacta acactgaaat tttatctaaa ggtatcgaac aaggtattgg taactcaatc 1020 ttaatcaaag taaaccaaat cggtacatta actgaaacat tcgatgctat tgaaatggct 1080 caaaaagctg gatatactgc ggttgtatct caccgttctg gtgaaactga agatactaca 1140 attgctgata tcgcagttgc tacaaatgca ggccaaatta aaacaggttc attatctaga 1200 actgaccgta ttgctaaata caatcaatta ttacgtattg aagatgaatt atacgaaaca 1260 gctaaatttg aaggaattaa atctttctac aatttagata aataa 1305 38 768 DNA S. aureus 38 atgaaaaaaa tcgttacagc tacaatcgct acagcaggac ttgccactat cgcatttgca 60 ggacatgatg cacaagccgc agaacaaaat aacaatggat ataattctaa tgacgctcaa 120 tcatacagct atacgtatac aattgatgca caaggtaatt atcattacac ttggacagga 180 aattggaatc caagtcaatt aacgcaaaac aacacatact actacaacaa ctacaatact 240 tatagttata acaatgcatc ttacaataac tactataatc attcatatca atacaataac 300 tatacaaaca atagccaaac agcaacaaat aactattata ctggtggttc aggtgcaagt 360 tatagcacaa caagtaataa tgttcatgtg actacaactg cagcgccatc ttcaaatggt 420 cgttcaattt ctaatggtta tgcatcagga agtaacttat atacttcagg acaatgtact 480 tattatgtat ttgatcgtgt tggtgggaaa attggttcaa catggggtaa cgcaagtaat 540 tgggctaacg cagctgcatc atctggctat acagtgaaca atacaccaaa agttggtgct 600 atcatgcaaa caacacaagg ctattacggt catgttgctt acgttgaagg cgttaacagc 660 aacggttctg ttcgtgtttc agaaatgaac tatggacatg gtgctggtgt ggttacgtct 720 cgtacaattt cagcaaacca agcaggttca tataatttca ttcattaa 768 39 804 DNA S. aureus 39 atgaagaaaa tcgctacagc tactatcgca actgcaggat tcgctacaat cgcaattgca 60 tcaggaaatc aagctcatgc ttctgagcaa gataactacg gttataatcc aaacgaccca 120 acatcatata gctatactta cactattgat gcacaaggta actaccatta cacatggaaa 180 ggtaactggc atccaagtca attaaaccaa gataatggct actacagcta ttactactac 240 aatggctaca ataactacaa caattacaac aatggttata gctacaataa ttacagccgt 300 tacaacaact actcaaataa taatcaatca tataactaca ataactataa tagttacaac 360 acaaacagct accgtactgg tggtttaggt gcaagctaca gcacttcaag caacaatgtt 420 caagtaacta caactatggc tccatcatca aatggccgtt caatctcaag tggttatact 480 tcaggacgta acttatacac ttctggtcaa tgtacatact acgtatttga tcgtgtaggt 540 ggtaaaatcg gttcaacttg gggcaatgca agtaactggg ctaacgcagc tgcaagagct 600 ggttacacag tgaacaatac accaaaagct ggtgcaatta tgcaaacaac tcaaggtgca 660 tacggtcacg ttgcatacgt tgaaagtgtt aacagcaatg gttcagtaag agtttcagaa 720 atgaactatg gttatggccc aggtgttgta acttcacgta caatctcagc tagccaagct 780 gctggttata acttcattca ctaa 804 40 774 DNA S. epidermidis 40 atgaaaaaaa tcgctacagc tacaattgca actgcaggaa tcgctacttt cgcatttgca 60 caccatgacg cacaagcagc agaacaaaat aatgatgggt acaatccaaa cgacccttat 120 tcatatagct acacttacac aatcgatgct gaaggtaact accactacac ttggaaaggt 180 aactggagtc cagatcgtgt aaatacttca tataactata ataattataa taactacaac 240 tactatggtt acaataacta tagcaactac aataactaca gtaattacaa caattacaac 300 aactatcaat caaacaacac gcaatcacaa agaacaactc aaccgactgg tggtttaggc 360 gcaagctatt caacatcaag tagtaatgtt cacgttacaa caacttctgc gccatcatca 420 aacggtgtat ctttatcaaa cgctcgctca gcatctggta acttatacac ttcaggtcaa 480 tgtacatatt atgtatttga cagagtaggt ggcaaaatcg gttcaacgtg gggtaacgca 540 aacaactggg caaacgctgc agcacgttct ggttacacag taaacaattc gcctgctaaa 600 ggtgcaatct tacaaacgtc acaaggtgca tacggacacg tagcatacgt tgaaggtgta 660 aacagcaatg gttcaatcag agtttcagaa atgaactacg gtcacggtgc aggtgttgtc 720 acttcacgta caatctctgc gagccaagct gcttcatata actatattca ctaa 774 41 930 DNA S. aureus 41 atgaaaaaat tagtaccttt attattagcc ttattacttc tagttgctgc atgtggtact 60 ggtggtaaac aaagcagtga taagtcaaat ggcaaattaa aagtagtaac gacgaattca 120 attttatatg atatggctaa aaatgttggt ggagacaacg tcgatattca tagtattgta 180 cctgttggtc aagatcctca tgaatatgaa gttaaaccta aagatattaa aaagttaact 240 gacgctgacg ttattttata caacggatta aatttagaga ctggtaacgg ttggtttgaa 300 aaagccttag aacaggctgg taaatcatta aaagataaaa aagttatcgc agtatcaaaa 360 gatgttaaac ctatctattt aaacggtgaa gaaggcaaca aagataaaca agatccacac 420 gcatggttaa gtttagataa tggtattaaa tacgtaaaaa caattcaaca aacatttatc 480 gataacgaca aaaaacataa agcagattat gaaaagcaag gtaacaaata cattgctcaa 540 ttggaaaaat taaataatga cagtaaagac aaatttaatg acattccaaa agaacaacgt 600 gccatgatta caagtgaagg tgccttcaag tacttctcaa aacaatacgg tattacacca 660 ggttatattt gggaaattaa cactgaaaaa caaggtacac ctgaacaaat gagacaagct 720 attgagtttg ttaaaaagca caaattaaaa cacttattag tagaaacaag tgttgataag 780 aaagcaatgg aaagtttatc tgaagaaacg aagaaagata tctttggtga agtgtacaca 840 gattcaatcg gtaaagaagg cactaaaggt gactcttact acaaaatgat gaaatcaaat 900 attgaaactg tacacggaag catgaaataa 930 42 930 DNA S. epidermidis 42 gtgaaaaaaa ttctcgcttt agcaatagca tttttaatta tccttgccgc atgtgggaat 60 cacagtaacc atgaacatca ctcacatgaa ggaaaattaa aagttgtaac tacaaactct 120 attctctatg acatggttaa acgtgtcggt ggaaataagg tcgatgttca tagcatcgtt 180 ccagtaggac aagacccaca tgaatatgag gttaaaccta aagatattaa agcattaaca 240 gatgctgacg ttgtatttta taacggttta aacctagaaa ctggaaatgg ttggtttgaa 300 aaagcacttg accaagcagg aaaatcaaca aaagataaaa atgtgatagc agcatcaaat 360 aatgttaaac caatatactt aaatggtgag gaaggtaaca aaaacaaaca agatccacat 420 gcatggttaa gtttagagaa tggaattaaa tacgtaaaaa caatacaaaa atcactagaa 480 catcatgata aaaaagataa gtctacatat gaaaaacaag ggaatgcata tatatcaaaa 540 ttagaagaac ttaataaaga tagtaaaaat aaatttgatg acatacccaa aaatcaacgt 600 gccatgatga caagtgaagg tgcatttaaa tattttgctc aacaattcga tgttaaacca 660 ggttatattt gggagataaa cacagaaaaa caaggtacac ctggtcaaat gaaacaagcc 720 attaaatttg ttaaagataa tcatttaaaa catttattag tcgaaacaag cgtagataaa 780 aaagctatgc aaagtttatc agaagaaact aagaaagata tttatggtga agtatttacc 840 gactctatag gtaaggaagg tactaaaggt gactcatact ataaaatgat gaaatctaat 900 attgatacaa tacatggtag tatgaaataa 930 43 702 DNA S. aureus 43 atgaaaaaga caattatggc atcatcatta gcagtggcat taggtgtaac aggttacgca 60 gcaggtacag gacatcaagc acacgctgct gaagtaaacg ttgatcaagc acacttagtt 120 gacttagcgc ataatcacca agatcaatta aatgcagctc caatcaaaga tggtgcatat 180 gacatccact ttgtaaaaga tggtttccaa tataacttta cttcaaatgg tactacatgg 240 tcatggagct atgaagcagc taatggtcaa actgctggtt tctcaaacgt tgcaggtgca 300 gactacacta cttcatacaa ccaaggttca gatgtacaat cagtaagcta caatgcacaa 360 tcaagtaact caaacgttga agctgtttca gctccaactt accataacta cagcacttca 420 actacttcaa gttcagtgag attaagcaat ggtaatactg caggtgctac tggttcatca 480 gcagctcaaa tcatggctca acgtactggt gtttcagctt ctacatgggc tgcaatcatc 540 gctcgtgaat caaatggtca agtaaatgct tacaacccat caggtgcttc aggtttattc 600 caaactatgc caggttgggg tccgacaaac actgttgacc aacaaatcaa cgcagctgtt 660 aaagcataca aagcacaagg tttaggtgct tggggattct aa 702 44 708 DNA S. epidermidis 44 atgaaaaaaa cagttatcgc ttctacatta

gcagtatctt taggaattgc aggttacggt 60 ttatcaggac atgaagcaca cgcttcagaa actacaaacg ttgataaagc acacttagta 120 gatttagcac aacataatcc tgaagaatta aatgctaaac cagttcaagc tggtgcttac 180 gatattcatt tcgtagacaa tggataccaa tacaacttca cttcaaatgg ttctgaatgg 240 tcatggagct acgctgtagc tggttcagat gctgattaca cagaatcatc atcaaaccaa 300 gaagtaagtg caaatacaca atctagtaac acaaatgtac aagctgtttc agctccaact 360 tcttcagaaa gtcgtagcta cagcacatca actacttcat actcagcacc aagccataac 420 tacagctctc acagtagttc agtaagatta tcaaatggta atactgctgg ttctgtaggt 480 tcatatgctg ctgctcaaat ggctgcacgt actggtgtat ctgcttcaac atgggaacac 540 atcattgcta gagaatcaaa tggtcaatta catgcacgta atgcttcagg tgctgctgga 600 ttattccaaa ctatgccagg ttggggttca actggttcag taaatgatca aatcaatgcc 660 gcttataaag catataaagc acaaggttta tctgcttggg gtatgtaa 708 45 11670 DNA S. aureus 45 gtgaattatc gtgataaaat tcaaaagttt agtattcgta aatatacagt tggtacattt 60 tcaactgtca ttgcgacatt ggtattttta ggattcaata catcacaagc acatgctgct 120 gaaacaaatc aaccagcaag cgtggttaaa cagaaacaac aaagtaataa tgaacagact 180 gagaatcgag aatctcaagt acaaaattct caaaattcac aaaatagtca atcattatcc 240 gctactcatg aaaatgagca accaaataat agtcaagcta atttagtaaa tcaaaaagta 300 gcgcaatcat ctactactaa tgatgaacaa ccagcatctc aaaatgtaaa tacaaagaaa 360 gattcggcaa cggctgcgac aacacaacca gataaagaag aaagtaagca taaacaaaac 420 gaaagtcaat ctgctaataa aaatggaaac gacaatagag cggctcatgt agaaaatcat 480 gaagcaaatg tagtaacagc ttcagattca tctgataatg gtaacgtaca acatgaccga 540 aatgaattac aagcattttt tgatgcaaat tatcatgatt atcgctttat tgaccgtgaa 600 aatgcagatt ctggcacatt taactatgta aaaggcattt ttgacaagat taatacttta 660 ttaggcagta atgatccaat taacaataaa gacttgcaac ttgcatacaa agaattggaa 720 caagctgttg ctttaattcg tacaatgcct caacgtcaac aaactagccg tcgatcaaac 780 agaattcaaa cgcgttctgt tgagtctaga gctgcagagc ctagatcagt atcagactat 840 caaaatgcaa attcatcata ttatgttgaa aatgctaatg atggttcagg atatcctgta 900 ggtacatata tcaatgcttc tagtaaaggg gcgccatata atttaccaac tacaccatgg 960 aatacattga aggcctctga ctcaaaggaa attgctctta tgacagcgaa acaaactgga 1020 gatggctacc aatgggttat taagtttaat aaaggacatg ctccacatca aaatatgatt 1080 ttctggtttg cattaccagc agaccaagtg ccagtaggaa gaactgactt tgtaacagtt 1140 aattcagatg gaacaaatgt acaatggagt catggagcag gagcaggtgc aaataaacca 1200 cttcaacaaa tgtgggaata tggagtaaat gatcctgatc gttcacatga ctttaaaata 1260 agaaatagaa gtggccaagt aatatatagc tggccaactg tccatgttta ttctttagaa 1320 gatttatcta gagcgagtga ttattttagt gaagctggag cgacacctgc tactaaagca 1380 tttggtagac aaaattttga atatattaat ggtcaaaaac ctgctgaatc accgggtgtt 1440 cctaaagttt atactttcat cggtcaaggt gatgcaagtt atacaatttc atttaaaaca 1500 caaggtccaa ctgttaataa attgtattat gcagcaggtg ggcgtgcttt agagtacaat 1560 caattattta tgtacagtca actatacgtc gaatcaacgc aagaccatca acaacgtctt 1620 aatggtttaa gacaagtggt taatcgtaca tatcgcatag gtacaactaa acgtgtagaa 1680 gtgagtcaag gaaatgtaca aacgaaaaag gtattagaaa gtacaaacct aaatatagat 1740 gattttgttg atgatccttt aagttatgtt aagacgccga gtaataaagt gttaggtttt 1800 tacccaacta atgcaaatac taacgctttt agaccggggg gcgttcaaga attaaatgaa 1860 tatcaattaa gtcaattatt tactgatcaa aaattacaag aagcagcaag aactagaaac 1920 ccaataagat taatgattgg tttcgactat cctgatggtt atggtaatag tgaaacttta 1980 gttcctgtta acttaacggt attacctgaa atccaacata atattaaatt ctttaaaaat 2040 gacgatactc aaaatattgc tgaaaaacca ttttcaaaac aagctgggca tccagttttc 2100 tatgtatatg caggtaacca agggaatgct tccgtgaatt taggtggtag cgtaacatct 2160 attcaaccat tacgtattaa tttaacaagt aatgagaatt ttacagataa agattggcaa 2220 attacaggta ttccgcgtac attacacatt gaaaactcga caaatagaac taataatgct 2280 agagaacgta acattgaact tgttggtaat ttattaccag gggattactt tggtacgata 2340 cgttttggac gtaaagaaca attatttgaa attcgtgtta aaccacatac accaacaatt 2400 acaacgacag ctgagcaatt aagaggtaca gcattacaaa aagtgcctgt taatatttcg 2460 ggaataccgt tggatccatc ggcattggtt tatttagttg caccaacaaa tcaaactacg 2520 aatggtggta gtgaggcaga tcaaatacca tctggttata cgatacttgc gactggtaca 2580 cctgatgggg tgcataatac aattactata cgaccgcaag attatgttgt attcatacca 2640 cctgtaggta aacaaattag agcagtagtt tattataata aagtagttgc atctaatatg 2700 agtaatgctg ttactatttt gccagatgac attccaccaa caatcaataa tcctgttgga 2760 ataaatgcca aatactatcg aggcgacgaa gtcaacttta caatgggagt ctctgataga 2820 cattctggta taaaaaatac aactattact actttgccaa gtggttggac atcaaattta 2880 actaaatccg acaacaaaaa cggctcatta gctattacag gtagagtctc tatgaatcag 2940 gcatttaaca gtgatattac atttaaagta tcagcgacag acaatgtcaa taatacgaca 3000 aatgatagtc aatctaaaca tgtgtcaatt catgtaggta aaattagtga agatgctcat 3060 ccgattgtat taggaaatac tgagaaagtt gtagtagtca atccgactgc tgtatctaat 3120 gatgaaaagc aaagcataat tactgccttt atgaataaaa accaaaatat aagaggatat 3180 ttagcatcaa ctgatccagt aactgtcgat aataatggta acgtcacatt acattaccgt 3240 gatggctcat caacaacgct tgatgctaca aatgtgatga catacgaacc agttgtgaaa 3300 tctgaatatc aaactgccaa tgctgctaaa acagcaacgg taacgattgc taaaggacaa 3360 tcatttaata ttggtgatat taaacaatat tttactttaa gtaatggaca agctattcca 3420 aatggcacat ttacaaatat tacatctgat agaactattc caactgcaca agaagttagt 3480 caaatgaatg caggtacgca gttatatcat atagttgctt caaatgcata tcataaagac 3540 actgaagatt tctatattag tttaaaaatc gttgatgtga aacaacctga aggcgatcaa 3600 cgtgtctatc gtacgtcaac atatgattta accactgatg aaatctcaaa agtaaaacaa 3660 gcttttatta atgcaaatag agatgtaatt acgcttgccg aaggtgatat ttcagttaca 3720 aatacaccta atggtgctaa tgtaagtact attacagtaa atattaataa aggtcgatta 3780 acgaaatcat tcgcgtctaa cctagctaat atgaatttct tgcgttgggt taatttccca 3840 caagattata cagtgacatg gacgaatgca aaaattgcaa acagaccaac agatggtggt 3900 ttatcatggt ccgatgacca taaatcttta atttatcgtt atgatgctac attaggcaca 3960 caaattacaa ctaatgatat tttaacgatg ctaaaagcga ctactacagt gcctggattg 4020 cgtaataata ttactggtaa tgaaaaagca caagcagaag caggtggaag accaaactat 4080 agaacaactg gttattcaca atcaaatgcg acaactgatg gtcaacgtca atttacgttg 4140 aatggtcaag tgattcaaat attagacatc atcaaccctt caaacggtta tggtgggcaa 4200 cctgttacaa attcaaatac tcgtgcaaac catagtaact caactgttgt taacgtaaac 4260 gaaccggcag ctaatggtgc tggcgcattt acaattgacc acgttgtaaa aagtaattct 4320 acacataatg caagtgatgc agtttataaa gcgcagttat acttaacgcc atatggtcca 4380 aaacaatatg ttgaacattt aaatcaaaat acaggaaata ctactgacgc tattaacatt 4440 tattttgtac caagtgactt agtgaatcca acaatttcag taggtaatta cactaatcat 4500 caagtgttct caggtgaaac atttacaaat acgattacag cgaatgataa ctttggtgtg 4560 caatcggtaa ctgtaccaaa tacatcacaa attacaggta ctgttgataa taaccatcaa 4620 catgtttctg caacggcacc aaatgtgaca tcagcaacta gtaagacaat caatttatta 4680 gcaactgata caagtggtaa tacagctaca acttcattca atgtaacagt gaaacctttg 4740 cgtgataaat atcgagttgg tacttcatca acggctgcta atcctgttag aattgccaat 4800 atttcgaata atgcgacagt atcacaagct gatcaaacga caattattaa ttcgttaacg 4860 tttacaagta atgcaccaaa tagaaactat gcaacagcaa gcgcaaatga aatcactagt 4920 aaaacagtta gtaatgtcag tcgtactgga aataatgcca atgtcacagt aactgttact 4980 catcaagatg gaacaacatc aacagtgact gtacctgtaa agcatgtcat tccagaaatc 5040 gttgcacatt cgcattacac tgtacaaggc caagacttcc cagcaggtaa tggttctagt 5100 gcagcagatt actttaagtt atctaatggt agtgccattc cagatgcaac gattacatgg 5160 gtaagtggac aagcgccaaa taaagataat acacgtattg gtgaagatat aacagtaact 5220 gcacatatct taattgatgg cgaaacaacg ccgattacga aaacagcaac atataaagta 5280 gtaagaactg taccgaaaca tgtctttgaa acagccagag gtgttttata cccaggtgtt 5340 tcagatatgt atgatgcgaa acaatatgtt aagccagtaa ataattcttg gtcgacaaat 5400 gcgcaacata tgaattttca atttgttgga acatatggtc ctaacaaaga tgttgtaggt 5460 atatcaacgc gtcttattag agtgacttat gataatagac aaactgaaga tttaactatt 5520 ttatctaaag ttaaacctga cccaccaaga attgacgcaa actctgtgac atataaagca 5580 ggtcttacaa accaagaaat taaagttaat aacgtattaa ataactcgtc agtaaaatta 5640 tttaaagcag ataatacacc attaaatgtc acaaatatta ctcatggtag tggttttagt 5700 tcggttgtga cagtaagtga cgcgttacca aatggcggaa ttaaagcaaa atcttcaatt 5760 tcaatgaaca atgtgacgta tacgacgcaa gacgaacatg gtcaagttgt tacagtaaca 5820 agaaatgaat ctgttgattc aaatgatagt gcttctgtta cagtaacacc acaattacaa 5880 gcaactactg aaggcgctgt atttattaaa ggtggcgacg gttttgattt cggtcatgta 5940 gaacgattta ttcaaaatcc gccacatggg gcaacggtcg catggcatga tagtccagat 6000 acatggaaga atacagtcgg caacacacat aaaactgcgg ttgtaacatt acctagtggt 6060 caaggtacgc gtaatgttga agttccagtc aaagtttatc cagttgctaa tgctaaggcg 6120 ccatcacgtg atgtgaaagg tcaaaatttg acacatggta caaacgctat tgattacatt 6180 acatttgatc caaatactaa tacgaatggt attacagcag catgggcaaa tagacaacaa 6240 ccaaataacc agcaagcagg cgttcaacat ttaaatgtcg atgtcacata tccaggtatt 6300 tcagctgcta aacgagttcc tgtaactgtg aacgtatatc aatttgaatt ccctcaaact 6360 acttatacaa caacagttgg tggcacttta gcaagtggta cgcaagcatc aggatatgca 6420 catatgcaaa acgcttcagg tttaccaaca gatggattta cgtataaatg gaatcgtgat 6480 actacgggta caaacgatgc aaactgggca gcaatgaata aaccaaatac tgcacaagtc 6540 gttaatgcaa aatatgatgt catctataat ggacatacat ttgcaacatc tttaccagcg 6600 aaatttgtag taaaagatgt tcaaccagcg aaaccaactg tcactgaaac agcggcagga 6660 gcgattacaa ttgcacctgg tgcgaaccaa acagtcaata ctcatgctgg taatgttacg 6720 acatatgctg acaaattagt tattaaacgt aatggaaatg ttgtaacgac atttacacgt 6780 cgtaataata cgagcccatg ggtgaaagaa gcatcagcag ataatgtaac aggtattgtt 6840 ggaactaata atggtattac tgtggcagca ggtactttca atcctgctga tacaattcaa 6900 gttgttgcaa cacaaggtag tggcgaaaca atcagtgacg agcaacgtag tgatgatttc 6960 acagttgtcg caccacaacc gaaccaagcg actacgaaaa tttggcaaaa tggtcatatt 7020 gatatcacgc ctaataatcc atcaggacat ttaattaatc caacacaagc aatggatatt 7080 gcttacactg aaaaagtggg taatggtgca gaacatagta agacaattaa tgttgttcgt 7140 ggtcaaaata atcaatggac aattgcgaat aagcctgact atgtaacgtt agatgcacaa 7200 actggtaaag tgacgttcaa tgccaatact ataaaaccaa attcatcaat cacaattact 7260 ccgaaagcag gtacaggtca ctcagtaagt agtaatccaa gtacattaac tgcaccggca 7320 gctcatactg tcaacacaac tgaaattgtg aaagattatg gttcaaatgt aacagcagct 7380 gaaattaaca atgcagttca agttgctaat aaacgtactg caacgattaa aaatggcaca 7440 gcaatgccta ctaatttagc tggtggtagc acaacgacga ttcctgtgac agtaacttac 7500 aatgatggta gtactgaaga agtacaagag tccattttca caaaagcgga taaacgtgag 7560 ttaatcacag ctaaaaatca tttagatgat ccagtaagca ctgaaggtaa aaagccaggt 7620 acaattacgc agtacaataa tgcaatgcat aatgcgcaac aacaaatcaa taccgcgaaa 7680 acagaagcac aacaagtgat taataatgag cgtgcaacac cacaacaagt ttctgacgca 7740 ctaactaaag ttcgtgcagc acaaactaag attgatcaag ctaaagcatt acttcaaaat 7800 aaagaagata atagccaatt agtaacgtct aaaaataact tacaaagttc tgtgaaccaa 7860 gtaccatcaa ctgctggtat gacgcaacaa agtattgata actataatgc gaagaagcgt 7920 gaagcagaaa ctgaaataac tgcagctcaa cgtgttattg acaatggcga tgcaactgca 7980 caacaaattt cagatgaaaa acatcgtgtc gataacgcat taacagcatt aaaccaagcg 8040 aaacatgatt taactgcaga tacacatgcc ttagagcaag cagtgcaaca attgaatcgc 8100 acaggtacaa cgactggtaa gaagccggca agtattactg cttacaataa ttcgattcgt 8160 gcacttcaaa gtgacttaac aagtgctaaa aatagcgcta atgctatcat tcagaagcca 8220 ataagaacag tgcaagaggt acaatctgcg ttaacaaatg taaatcgtgt caatgagcga 8280 ttaacgcaag caattaatca attagtacct ttagctgata atagtgcttt aagaactgct 8340 aagacgaaac ttgatgaaga aatcaataaa tcagtaacta ctgatggtat gacacaatca 8400 tcaatccaag catatgaaaa tgctaaacgt gcaggtcaaa cagaaacaac aaatgcacaa 8460 aatgttatta acaatggtga cgcgacagac caacaaattg ccgcagaaaa aacaaaagta 8520 gaagaaaaat ataatagctt aaaacaagca attgctggat taacaccaga cttggcacca 8580 ttacaaactg caaaaactca gttgcaaaat gatattgatc agccaacgag tacgactggt 8640 atgacaagcg catctgttgc tgcatttaat gacaaacttt cagcagctag aactaaaatt 8700 caagaaattg atcgcgtact agcatctcat ccagatgtag caacgattcg tcaaaacgtg 8760 acagcagcga atgctgctaa aacagcactt gatcaagcgc gcaatggctt aacagtcgat 8820 aaagcacctt tagaaaatgc gaaaaatcaa ctacaacata gtattgatac gcaaacaagt 8880 acaactggta tgacacaaga ctctataaat gcatacaatg cgaagttaac agctgcacgt 8940 aataaggttc aacaaatcaa tcaagtatta gcaggttcac ctactgtaga tcaaattaat 9000 acaaatacgt ctgcagcaaa tcaagcgaaa tctgatttag atcatgcacg tcaagcgtta 9060 acaccagata aagcgccgct tcaaaatgcg aaaacgcaat tagaacaaag cattaatcaa 9120 ccaacagata caacaggtat gacaaccgct tcgttaaatg catacaacca aaaattacaa 9180 gcagcacgtc aaaagttaac tgaaattaat caagtgttga atggcaaccc aactgtccaa 9240 aatatcaatg ataaagtggc agaggcaaac caagctaagg atcaattaaa tacagcacgt 9300 caaggtttaa cattagatag acagccagcg ttaacaacat tacatggtgc atctaactta 9360 aaccaagcac aacaaaataa tttcacgcaa caaattaatg ctgctcaaaa tcatgctgcg 9420 cttgaaacaa ttaagtctaa cattacggct ttaaatactg cgatgacgaa attaaaagac 9480 agtgttgcgg ataataatac aattaaatca ggtcaaaatt acactgacgc aacaccagct 9540 aataaacaag cctatgataa tgcagttaat gcggctaaag gtgtcattgg agaaacgact 9600 aatccaacga tggatgttaa cacagtgaac caaaaagcag catctgttaa atcgacgaaa 9660 gatgctttag atggtcaaca aaacttacaa cgtgcgaaaa cagaagcaac aaatgcgatt 9720 acgcatgcaa gtgatttaaa ccaagcacaa aagaatgcat taacacaaca agtgaatagt 9780 gcacaaaacg tgcaagcagt aaatgatatt aaacaaacga ctcaaagctt aaatactgct 9840 atgacaggtt taaaacgtgg cgttgctaat cataaccaag tcgtacaaag tgataattat 9900 gtcaacgcag atactaataa gaaaaatgat tacaacaatg catacaacca tgcgaatgac 9960 attattaatg gtaatgcaca acatccagtt ataacaccaa gtgatgttaa caatgcttta 10020 tcaaatgtca caagtaaaga acatgcattg aatggtgaag ctaagttaaa tgctgcgaaa 10080 caagaagcga atactgcatt aggtcattta aacaatttaa ataatgtaca acgtcaaaac 10140 ttacaatcgc aaattaatgg tgcgcatcaa attgatgcag ttaatacaat taagcaaaat 10200 gcaacaaact tgaatagtgc aatgggtaac ttaagacaag ctgttgcaga taaagatcaa 10260 gtgaaacgta cagaagatta tgcggatgca gatacagcta aacaaaatgc atataacagt 10320 gcagtttcaa gtgctgaaac aattattaat caaacagcta atccgacaat gtctgttgat 10380 gatgttaatc gtgcaacttc agctgttact actaataaaa atgcattaaa tggtgatgaa 10440 aaattagtac aatctaaaac agatgctgca agagcaattg atgcattacc acatttaaat 10500 aatgcacaaa aagcagatgt taaatctaaa attaatgctg catcaaatat tgctggtgta 10560 aataccgtta aacaacaagg tacagattta aatacagcga tgggtaactt gcagggtgca 10620 atcaatgatg aacaaacgac gcttaatagt caaaattatc aagatgcgac acctagtaag 10680 aaaacagcat acacaaatgc ggtgcaagct gcgaaagata ttttaaataa atcaaatggt 10740 caaaataaaa cgaaagatca agttactgaa gcgatgaatc aagtgaattc ggctaaaaat 10800 aacttagatg gtacgcgttt attagatcaa gcgaagcaaa cagcgaaaca gcagttaaat 10860 aatatgacgc atttaacaac tgcacaaaaa acgaatttaa caaatcaaat taatagtggt 10920 actactgttg ctggtgttca tacggttcaa tcaaatgcca acacattaga tcaagcgatg 10980 aatacgttaa gacaaagtat tgctaacaat gatgcgacta aagcaagtga agattacgta 11040 gatgctaata atgataagca aacagcatat aacaacgcgg tagctgctgc tgaaacgatt 11100 attaatgcga atagtaatcc agaaatgaat ccaagtacga ttacacaaaa agcagagcaa 11160 gtgaatagtt ctaaaacggc acttaacggt gatgaaaact tagctacggc aaaacaaaat 11220 gcgaaaacgt acttaaacac attaacgagt attacagatg ctcaaaagaa caatttgatt 11280 agtcaaatta gtagtgcgac aagagtgagt ggtgttgata ctgtaaaaca aaatgcacaa 11340 catttagatc aagctatggc taacttacaa aatggtatta acaacgaatc tcaagtgaaa 11400 tcatctgaga aatatcgtga tgctgataca aataaacaac aagagtatga taatgctatt 11460 actgcagcga aagcgatttt aaataaatcg acaggtccaa acactgcgca aaatgcagtt 11520 gaagcagcat tgcaacgtgt taatactgcg aaagatgcat tgaatggtga tgcaaaatta 11580 attgcagctc aaaacgcagc gaaacaacat ttaggtactt taacgcatat cactacagca 11640 caacgcaatg atttaacaaa tcaaatttca 11670 46 20139 DNA S. aureus 46 atgggtaact tacaaacggc tatcaacgat aagtcaggaa cattagcgag ccaaaacttc 60 ttggatgctg atgagcaaaa acgtaatgct tacaatcaag ctatatcagc tgccgaaacc 120 attttaaata aacaaactgg accgaataca gcgaaaacag cggttgaaca agcacttaat 180 aatgttaata gtgcgaaaca tgcattaaat ggtacgcaaa acttaaataa tgcgaaacaa 240 gcagcgatta cagcaattaa tggcgcatct gatttaaatc aaaaacaaaa agatgcatta 300 aaagcacaag ctaatggtgc tcaacgcgta tctaatgcaa atgatgtaca acgtaatgcg 360 actgaactga acacggcaat gggtcaatta caacatgcca tcgcagataa gacgaatacg 420 ttagcaagca gtaaatatgt caacgccgat agcactaaac aaaatgctta cacaactaaa 480 gttaccaatg ctgaacatat tattagcggt acgccaacgg ttgttacaac accttcagaa 540 gtaacagctg cagctaatca agtaaacagc gcgaaacaag aattaaatgg tgacgaaaga 600 ttacgtgttg caaaacaaaa cgccaatact gctattgatg cattaacgca attaaatact 660 cctcaaaaag ctaaattaaa agaacaagtg ggacaagcca atagattaga agacgtacaa 720 tctgttcaaa caaatggaca atcattgaac aatgcaatga aaggcttaag agatagtatt 780 gctaacgaaa caacagtcaa agcaagtcaa aactatacag acgcaagtcc gaataaccaa 840 tcaacatata atagcgctgt gtcaaatgcg aaaggtatca ttaatcaaac taacaatcca 900 actatggata ctagtgcgat tacccaagct acaacacaag tgaataatgc taaaaatggt 960 ttaaacggtg ctgaaaactt aagaaatgca caaaacactg ctaagcaaaa cttaaatacg 1020 ttatcacact taacaaataa ccaaaaatct gcaatctcat cacaaattga tcgtgcaggt 1080 catgtgagtg aggtaacagc tgctaaaaat gcagcaactg agttaaacgc gcaaatgggc 1140 aacttggaac aagctatcca tgatcaaaac acagttaaac aaggtgttaa cttcactgat 1200 gcagataaag ctaaacgtga tgcttataca aatgcggtaa gcagagcaga aacaattctg 1260 aataaaacgc aaggtgcaaa tacgtctaaa caagatgttg aagcggctat tcaaaatgtt 1320 acaagtgcta aaaatgcatt gaatggtgat caaaacgtta caaatgcgaa gaatgcagct 1380 aaaaatgcat taaataactt aacgtcaatt aataatgcac aaaaacgtga cttaacaact 1440 aaaattgatc aagcaacaac agtagctggt gttgaagcgg tatctaatac aggtacacaa 1500 ttgaatacag cgatggctaa cttgcaaaat ggtattaatg ataaagcgaa tactttagcg 1560 agcgaaaact atcatgatgc tgattcagat aagaaaactg cttatactca agccgttacg 1620 aacgcagaaa atattttaaa taaaaatagt ggatcaaatt tagataaagc tgccgttgaa 1680 aacgcgttgt cacaagtgac aaatgcgaaa ggtgccctaa atggtaacca taatttagag 1740 caagctaaat caaatgcaaa cactactata aacggccttc aacatttaac aacagcacaa 1800 aaagataaat tgaaacaaca agtgcaacaa gcacaaaatg ttgcaggtgt agatactgtt 1860 aaatcaagtg ccaacacatt aaatggtgct atgggtacgt taagaaatag catacaagat 1920 aacacagcta cgaaaaatgg ccaaaactat cttgatgcta cagaacgtaa caaaacaaac 1980 tataacaatg ctgttgatag tgctaatggt gtcattaatg caacaagcaa tccaaatatg 2040 gatgctaatg caattaacca aatcgctaca caagtgacat caacgaaaaa tgcattagat 2100 ggtacacata atttaacgca agcgaaacaa acagcaacaa atgccatcga tggtgctact 2160 aacttaaata aagcgcaaaa agatgcgtta aaagcacaag ttacaagtgc gcaacgtgtt 2220 gcaaatgtaa caagtatcca acaaactgca aatgaactta atacagctat gggtcaatta 2280 caacatggta ttgatgatga aaatgcaaca aaacaaactc aaaaatatcg tgacgctgaa 2340 caaagtaaga aaactgctta tgatcaagct gtagctgctg cgaaagcaat tttaaataaa 2400 caaacaggtt ccaattcaga taaagcagca gttgaccgtg cattacaaca agtaacaagt 2460 acgaaagatg cattgaatgg ggatgctaaa ctggcagaag cgaaagcggc agctagacaa 2520 aacttaggta ctttaaacca tattacgaat gcacaacgta ctgcgttaga aggtcaaatc 2580 aatcaagcga cgactgttga tggcgttaat actgtaaaaa

caaatgccaa tacattagac 2640 ggcgctatga atagcttaca aggtgcaatc aatgataaag atgcgacatt aagaaatcaa 2700 aattatcttg atgcagatga atcaaaacga aatgcatata cgcaagctgt cacagcggct 2760 gaaggcattt taaataaaca aacaggtggt aacacatcta aagcagacgt tgataatgca 2820 ttaaatgcag ttacaagagc gaaagcggct ttaaatggtg ctgaaaactt aagaaatgcg 2880 aaaacttcag caacaaatac gattaatggt ttacctaact taacacaatt acaaaaagac 2940 aacttgaagc atcaagttga acaagcgcaa aatgtagttg gtgtaaatgg tgttaaagat 3000 aaaggtaata cattaaatac tgccatgggt gcattacgta caagtatcca aaatgataat 3060 acgacgaaaa caagtcaaaa ttatcttgat gcatctgata gcaacaaaaa taattacaat 3120 actgctgtaa ataatgcaaa tggtgttatt aatgcaacga acaatccaaa tatggatgct 3180 aatgcgatta atgacatggc aaatcaagtc aatacaacaa aagcagcgtt aaatggtgca 3240 caaaacttag ctcaagctaa aacaaatgcg acgaacacaa ttaacaacgc gcaagactta 3300 aaccaaaaac aaaaagatgc attaaaaaca caagttaaca atgcacaacg tgtatctgat 3360 gcaaataacg ttcaacatac agctactgaa ttgaacggtg cgatgacagc acttaaagca 3420 gctattgcgg ataaagaaag aacaaaagca agcggtaatt atgtcaatgc tgatcaagaa 3480 aaacgtcaag cgtatgattc aaaagtgact aacgctgaaa atatcattaa tggtacacca 3540 aatgcgacat taacagtcaa tgacgtaaat agtgcggcat cacaagtcaa tgcggctaaa 3600 acagcattaa atggtgataa caacttacgt gtagcgaaag agcatgctaa caatacaatt 3660 gacggcttag cacaattgaa taatgtacaa aaagcaaaat taaaagaaca agttcaaagt 3720 gcaactacat tagatggtgt tcaaactgtt aaaaatagtt ctcaaacgtt gaatacagcg 3780 atgaaaggct taagagatag tattgcgaat gaagcaacga ttaaagcagg tcaaaactac 3840 actgacgcaa gtccaaataa tcgtaacgag tacgacagcg cagttactgc agcaaaagca 3900 atcattaatc aaacatcgaa cccaacgatg gaaccaaata ctattacgca agcaacatca 3960 caagtgacaa ctaaagaaca tgcattaaat ggtgcgcaaa acttagctca agctaagaca 4020 acagcgaaaa acaacttgaa taacttaaca tcaattaaca atgcacaaaa agatgcgtta 4080 acgcgtaaca ttgatggtgc aactacagta gctggtgtaa atcaagaaac tgcaaaagca 4140 acagaattaa ataacgcaat gcacagttta caaaatggta tcaatgatga gacacaaaca 4200 aaacaaactc agaaatacct agatgctgag ccaagtaaga aatcagctta tgatcaagca 4260 gtaaatgcag caaaagcaat tttaacaaaa gctagtggtc aaaatgtaga caaagcagca 4320 gttgaacaag cattacaaaa tgtgaacagt acgaagacgg cgttgaacgg tgatgcgaaa 4380 ttaaatgaag ctaaagctgc tgcgaaacaa acgttaggta cattaacaca cattaataat 4440 gcacaacgta atgcgttaga taatgaaatt acacaagcaa caaatgttga aggtgttaat 4500 acagttaaag ccaaagcgca acaattagat ggtgctatgg gtcaattaga aacatcaatt 4560 cgtgataaag acacgacgtt acaaagtcaa aattatcaag atgctgatga tgctaaacga 4620 acggcttatt ctcaagcagt aaatgcagca gcaactattt taaataaaac agctggagga 4680 aatacaccta aagcagatgt cgaaagagca atgcaagctg ttacacaagc caatactgca 4740 ttaaacggta ttcaaaactt agaacgtgcg aaacaggctg cgaacacagc gattacaaat 4800 gcttcggact taaatacaaa acaaaaagaa gcattgaaag cacaagtaac aagtgcagga 4860 cgcgtatctg cagcaaatgg tgttgaacat actgcgactg aattaaatac tgcgatgaca 4920 gctttaaaac gtgccattgc tgataaagct gacacaaaag ctagtggtaa ttatgtcaat 4980 gctgatgcga ataaacgcca agcatatgat gaaaaagtga cagctgcaga acatatcgtt 5040 agtggtacac caacaccaac gttaacacca tcagatgtta caaatgcagc aacgcaagta 5100 acgaatgcga agacgcagtt aaacggtaat cataatttag aagtagcgaa acaaaatgct 5160 aacacagcaa ttgatggttt aacttcttta aatggtccgc aaaaagcaaa acttaaagaa 5220 caagtgggtc aagcgacgac gttgccaaat gttcaaactg ttcgtgataa tgcacaaaca 5280 ttaaacactg caatgaaagg tctacgagat agcattgcga atgaagcaac gattaaagca 5340 ggtcaaaact acacagatgc aagtcaaaac aaacaaaatg actacaacaa tgcagtcact 5400 gcagcaaaag caatcattgg tcaaacaact agtccatcaa tgattgcgca agaaattaat 5460 caagcgaaag accaagtgac agctaaacaa caagcgttaa acggtcaaga aaacttaaga 5520 actgcgcaaa caaatgcgaa gcaacatttg aatggcttaa gtgacttaac taatgcacaa 5580 aaagatgcag cgaaacgcca aatcgaaggt gcaacgcatg ttaatgaagt aacacaagcg 5640 caaaataatg cggacgcatt aaatacagct atgacgaact tgaaaaatgg tattcaagat 5700 caaaatacga ttaagcaagg tgttaacttc actgatgcag atgaagcgaa acgtaatgca 5760 tatacaaatg cagtgacgca agctgaacaa attttaaata aagcacaagg tccaaatact 5820 gcaaaagacg gtgtcgaaac tgcgttacaa aatgtacaac gtgctaaaaa cgaattgaac 5880 ggtaatcaaa atgttgcgaa cgctaagaca actgcgaaaa atgcattgaa taaccttaca 5940 tcaattaata atgcacaaaa agcagcattg aaatcacaaa ttgaaggtgc gacaacagtt 6000 gcaggtgtaa atcaagtgtc tacaatggca tctgaattaa atactgcaat gagcaactta 6060 caacgtggta ttaatgacga agcagctaca aaagcagctc agaaatatac tgaagcagat 6120 agagataaac aaactgcata caatgatgct gtaacagcag ctaaaacgtt attagataaa 6180 acagctggtt caaatgacaa taaagtagcc gttgaacaag cattacaacg tgtgaatact 6240 gctaaaacag cattaaatgg tgacgcgcga ttaaatgaag cgaagaacac agctaaacaa 6300 caattagcga caatgtcaca tttaactaat gctcaaaaag caaacttaac agaacaaatt 6360 gaacgtggta caactgttgc tggtgttcaa ggcatccaag caaatgctgg tactttaaat 6420 caagcaatga atcaattaag acaaagtatt gcttctaaag atgcgactaa atcaagcgaa 6480 gattatcaag acgcgaatgc agatttacaa aatgcataca atgatgcggt aactaatgct 6540 gaaggtatta ttagtgcaac gaataaccct gaaatgaatc ctgatacaat taaccaaaaa 6600 gcgagccaag tgaacagtgc gaagtctgca ttgaacggtg atgaaaaatt agcagcagta 6660 aaacaaactg cgaaatcaga tatcggtcgt ttgacagact tgaacaatgc acaacgaact 6720 gcggcaaatg ctgaagtgga tcaagcacca aatcttgcag ctgtcacagc ggctaaaaat 6780 aaagcaacat cgttaaacac agcgatgggt aatttgaaac atgcacttgc tgaaaaggat 6840 aatacgaaac gtagtgtcaa ttacacagat gcggatcaac caaaacaaca agcgtatgat 6900 actgcagtta cacaagcaga agcaattact aatgcaaatg gcagtaacgc gaatgaaaca 6960 caagttcaag cagcgcttaa ccaattgaat caagctaaaa acgacttgaa tggtgataat 7020 aaagttgctc aagcgaaaga aacagcaaaa cgtgcattag cttcatatag taacttgaat 7080 aacgcgcaat caactgcagc aactagtcaa attgacaatg caacgacagt agcagacgta 7140 actgctgcac aaaatactgc taatgaatta aatacagcaa tgggtcaact tcaaaatggt 7200 attaatgacc aaaacactgt taaacaacaa gtgaacttta cagatgctga ccaaggtaag 7260 aaagatgctt acacaaatgc tgttacgaat gctcaaggta ttttagataa agcaaacggt 7320 caaaatatga caaaagcaca agttgaagct gcattaaatc aagtaacgac tgctaagaat 7380 gctttaaacg gtgatgcaaa tgtaagacaa gcaaaatcag atgcgaaagc aaacttaggt 7440 acattaacac acttaaataa tgcacaaaaa caagatttaa catcacaaat cgaaggtgca 7500 acaacagtca acggtgtaaa tagtgttaaa acgaaagcac aagacttaga tggtgcaatg 7560 caacgattag agtcagcaat cgcaaataaa gatcaaacta aagcgagcga aaactacatt 7620 gacgcagatc caactaagaa aacagcattt gataatgcca tcacacaagc tgaatcttac 7680 ttaaataaag atcatggtac gaataaagat aagcaagctg ttgaacaagc aattcaaagt 7740 gtaacgtcta ctgaaaatgc tttgaacggt gacgcgaact tacaatgcgc taaaactgaa 7800 gctacacaag ctatcgataa cttgacacaa ttgaatacac cgcaaaaaac agcattgaaa 7860 caacaagtga atgctgcaca acgcgtatca ggtgtaactg atctgaaaaa tagtgctaca 7920 tcacttaata atgcgatgga tcaattaaaa caagcaattg gtgatcatga cacaattgta 7980 gctggtggta attacactaa cgcaagtcct gataaacaag gtgcttacac tgatgcatat 8040 aatgctgcga agaatatcgt aaatggttca cctaatgtga ttacaaatgc agcagatgtt 8100 actgcggcaa cacaacgtgt caataatgct gaaacaagtt taaatggtga tacaaactta 8160 gcaactgcga agcaacaagc taaagatgca ttacgtcaaa tgacacattt atctgatgca 8220 caaaaacaaa gtattactgg tcaaattgat agcgcgacac aagtaactgg tgtacaaagt 8280 gtgaaagaca atgcaacaaa tcttgacaat gcaatgaatc aacttcgaaa tagtattgcg 8340 aataaagatg aagtaaaagc gagtcaacca tatgttgatg cagatacaga taaacaaaat 8400 gcatacaata cagcagttac aagtgctgaa aatatcatta atgcaacgag tcagccaaca 8460 cttgatccat ctgcagtaac acaagcagct aatcaagtga acactaacaa aactgcgctt 8520 aatggtgcgc aaaacttagc aaataaaaag caagaaacaa ctgctaacat caaccgatta 8580 agtcatttaa acaatgctca aaagcaagat ttaaatacac aagtgacaaa tgcaccaaat 8640 attagcacag taaatcaagt gaaaactaaa gctgaacaat tagatcaagc aatggaacgt 8700 ttaatcaacg gaatccaaga caaagatcaa gtgaaacaaa gtgttaactt tacagatgca 8760 gatccagaaa aacaaacagc atacaacaat gcggtaactg ctgctgaaaa tattattaat 8820 caagcaaatg gtacaaatgc gaaccaatca caagttgaag cagcactttc aactgtaaca 8880 actactaaac aagcgttgaa tggtgataga aaagtaacag atgctaaaaa caatgcaaac 8940 caaacattat ctacgttaga taacttaaac aatgcacaaa aaggtgctgt tactggaaac 9000 atcaatcaag cgcacactgt agctgaagta acgcaagcca ttcaaaccgc tcaggaactg 9060 aatacagcga tgggtaactt gaaaaatagc ttgaatgata aagacactac acttggcagt 9120 caaaactttg cagatgcaga tccagagaag aaaaatgcat acaatgaagc ggttcgtaat 9180 gctgaaaata ttttaaataa atctacaggt acgaacgtgc ctaaagatca agttgaagca 9240 gctatgaatc aagtgaatac tacaaaagca gcgcttaatg gtactcaaaa ccttgaaaaa 9300 gcgaaacaac acgcaaatac agcaattgac ggtttaagcc atttaacaaa tgcacaaaaa 9360 gaggcattaa aacaattggt acaacaatcg actactgttg cagaagcaca aggtaatgaa 9420 caaaaagcaa acaatgttga tgcagcaatg gacaaattac gtcaaagtat tgcagataat 9480 gcgacaacaa aacaaaacca aaattatact gatgcaagtc cgaataaaaa ggatgcgtac 9540 aataatgctg tcacaactgc acaaggtatt attgatcaaa ctacaaaccc ttcattagat 9600 ccgactgtta tcaatcaagc tgctggacaa gtaagcacgt ctaaaaatgc tttaaatggt 9660 aatgaaaact tagaggcagc gaagcaacaa gcaacgcaat ctttaggttc attagacaac 9720 ttaaataatg cgcaaaaaca agctgttact aatcaaatta atggcgcgca tactgttgat 9780 gaagcaaatc aaattaagca aaatgcgcaa aacttaaata ctgcgatggg taacttgaaa 9840 caagcgatag ctgataaaga tgctacgaaa gcaacagtta acttcactga tgcagatcaa 9900 gcaaaacaac aagcatataa cactgcagtt acaaatgctg aaaatatcat ttcaaaagct 9960 aatggtggta atgcaacaca aactgaagtt gaacaagcaa tccaacaagt aaatgcagca 10020 aaacaagcat taaatggtaa tgccaacgtt caacatgcaa aagacgaagc aacagcatta 10080 attaataact ctaatgatct taaccaagca cagaaagatg cattaaaaca acaagtacaa 10140 aatgcaacta ctgtagctgg tgtaaacaat gttaaacaaa cggcgcaaga gttaaacaat 10200 gcgatgacac aattaaaaca aggcattgca gataaagaac aaacaaaagc tgatggtaac 10260 tttgtcaatg cagattctga caagcaaaat gcatataatc aagcagtagc gaaagctgaa 10320 gcattaatta gtggtacgcc tgatgttgtc gttacaccta gcgaaattac tgcagcgtta 10380 aataaagtta cgcaagctaa aaatgattta aatggtaata caaacttagc aacggcgaaa 10440 caaaatgttc aacatgctat tgatcaattg ccaaacttaa accaagcgca acgtgatgaa 10500 tacagcaaac aaatcacgca agcaacactt gtaccaaacg tcaatgctat tcaacaagcg 10560 gcaacaacgc ttaatgacgc gatgacacaa ttgaaacaag gtattgcgaa taaagcacaa 10620 attaaaggta gcgagaacta tcacgatgct gatactgaca agcaaacagc atatgataat 10680 gcagtaacaa aagcagaaga attgttaaaa caaacaacaa atccaacaat ggatccaaat 10740 acaattcaac aagcattaac taaagtgaat gacacaaatc aagcacttaa cggtaatcaa 10800 aaattagctg atgccaaaca agatgctaag acaacacttg gtacactaga tcatttaaat 10860 gatgctcaaa aacaagcgct aacaactcaa gttgaacaag caccagatat tgcaacagtt 10920 aataatgtta agcaaaatgc tcaaaatctg aataatgcta tgactaactt aaacaatgca 10980 ttacaagata aaactgagac attaaatagc attaacttta ctgatgcaga tcaagctaag 11040 aaagatgatt atactaatgc ggtttcacat gcagaaggta ttttatctaa agcaaatggc 11100 agcaatgcaa gtcaaactga agtggaacaa gcgatgcaac gtgtgaacga agcgaaacaa 11160 gcattgaatg gtaatgacaa tgtacaacgt gcaaaagatg cagcgaaaca agtaattaca 11220 aatgcaaatg atttaaatca agcgcaaaaa gatgcattaa aacaacaagt cgatgctgcg 11280 caaactgttg caaatgtaaa cacgattaag caaacagcac aagatttaaa tcaagcaatg 11340 acacaattga aacaaggtat tgcagataaa gaccaaacta aagcaaatgg taactttgtc 11400 aatgctgata ctgataagca aaatgcatat aacaatgcgg tagcgcatgc tgaacaaatc 11460 attagtggta caccaaatgc aaacgtggat ccacaacaag tggctcaagc gttacaacaa 11520 gtgaatcaag ctaagggtga tttaaacggt aaccacaact tacaagttgc taaagacaat 11580 gcaaatacag ccattgatca gttaccaaac ttaaatcaac cacaaaaaac agcattaaaa 11640 gaccaagtgt cgcatgcaga acttgttaca ggtgttaatg ctattaagca aaatgctgat 11700 gcgttaaata atgcaatggg tacgttgaaa caacaaattc aagcgaatag tcaagtacca 11760 caatcagttg actttacaca agcggatcaa gacaaacaac aagcttataa caatgcagct 11820 aaccaagcgc aacaaatcgc aaatggcaca ccaacacctg tattggcgcc tgatacagta 11880 acaaaagcag ttacaactat gaatcaagcg aaagatgcat taaacggtga tgaaaaatta 11940 gcgcaagcga aacaagatgc tttagcaaat cttgatacgt tacgtgactt aaatcaacca 12000 caacgtgatg cattacgaaa ccaaatcaat caagcacaag ctttagctac agttgaacaa 12060 actaaacaaa atgcacaaaa tgtgaataca gcaatgggta acttgaaaca aggtattgca 12120 aataaagata ctgtgaaagc aagtgagaac taccacgatg ctgatgtcga taagcaaaca 12180 gcatatacaa atgcagtgtc tcaagcggaa ggtattatca atcaaacgac aaatccaacg 12240 cttaacccag atgacattac tcgtgcatta actcaagtga ctgatgctaa aaatagctta 12300 aacggtgaag ctaaattagc cactgaaaag caaaatgcta aagatgccgt aagtggaatg 12360 acgcatttaa acgatgctca aaaacaagca ttaaaaggtc aaatcgatca atcgcctgaa 12420 attgctacag tgaaccaagt taaacaaaca gcaacgagcc tagatcaagc aatggatcaa 12480 ttatcacaag ctattaatga taaagatcaa atattagcgg acggtaatta cttaaatgca 12540 gatcctgaca aacaaaatgc gtataaacag gcagtagcaa aagctgaagc attattgaat 12600 aaacaaagtg gtactaatga agtacaagca caagttgaaa gcatcactaa tgaagtgaac 12660 gcagcgaaac aagcattaaa tggtaatgac aatttggcaa atgcaaaaca acaagcaaaa 12720 caacaattgg cgaacttaac acacttaaat gatgcacaaa aacaatcatt tgaaagtcaa 12780 attacacaag cgccacttgt tacagatgtc actacgatta atcaaaaagc acaaacgtta 12840 gatcatgcga tggaattatt aagaaatagt gttgcggata atcaaacgac attagcgtct 12900 gaagattatc atgatgcaac tgcgcaaaga caaaatgact ataacaaagc tgtaacagct 12960 gctaataata tcattaatca aactacatcg cctacgatga atccagatga tgttaatggt 13020 gcaacgacac aagtgaataa tacgaaagtt gcattagatg gtgatgaaaa ccttgcagca 13080 gctaaacaac aagcaaacaa cagacttgat caattagatc atttgaataa tgcgcaaaag 13140 caacagttac aatcacaaat tacgcaatca tctgatattg ctgcagttaa tggtcacaaa 13200 caaacagcag aatctttaaa tactgcgatg ggtaacttaa ttaatgcgat tgcagatcat 13260 caagccgttg aacaacgtgg taacttcatc aatgctgata ctgataaaca aactgcttat 13320 aatacagcgg taaatgaagc agcagcaatg attaacaaac aaactggtca aaatgcgaac 13380 caaacagaag tagaacaagc tattactaaa gttcaaacaa cacttcaagc gttaaatgga 13440 gatcataatt tacaagttgc taaaacaaat gcgacgcaag caattgatgt tttaacaagc 13500 ttaaatgatc ctcaaaaaac agcattaaaa gaccaagtta cagctgcaac tttagtaact 13560 gcagttcatc aaattgaaca aaatgcgaat acgcttaacc aagcaatgca tggtttaaga 13620 cagagcattc aagataacgc agcaactaaa gcaaatagca aatatatcaa cgaagatcaa 13680 ccagagcaac aaaactatga tcaagctgtt caagccgcaa ataatattat caatgaacaa 13740 actgcaacat tagataataa tgcgattaat caagtagcgg caactgtgaa tacaacgaaa 13800 gcagcattac atggtgatgt gaaattacaa aatgataaag atcatgctaa acaaacggtt 13860 agccaattag cacatctaaa caatgcacaa aaacatatgg aagatacgtt aattgatagt 13920 gaaacaacta gaacagcagt taagcaagat ttgactgaag tacaagcatt agatcaactt 13980 atggatgcat tacaacaaag tattgctgac aaagatgcaa cacgtgcgag cagtgcatat 14040 gtcaatgcag aaccgaataa aaaacaagcc tatgatgaag cagttcaaaa tgctgagtct 14100 atcattgcag gattaaataa tccaactatc aataaaggta atgtatcaag tgcgactcaa 14160 gcagtaatat catctaaaaa tgcattagat ggtgttgaac gattagctca agataagcaa 14220 actgctggaa attctctaaa tcatttagat caattaacac cagctcaaca acaagcgcta 14280 gaaaatcaaa ttaataatgc aacaacttgt gataaagtgg ctgaaatcat tgcacaagcg 14340 caagcattaa atgaagcgat gaaagcatta aaagaaagta ttaaggatca accacaaact 14400 gaagcaagta gtaaatttat taacgaggat caagcgcaaa aagatgcata tacgcaagca 14460 gtacaacacg cgaaagattt gattaacaaa acaactgatc ctacattagc taaatcaatc 14520 attgatcaag cgacacaggc agtgactgat gctaaaaaca atttacatgg tgatcaaaaa 14580 ctagctcaag ataagcaacg tgcaacagaa acgttaaata acttgtctaa cttgaataca 14640 ccacaacgtc aagcacttga aaatcaaatc aataatgcag caactcgtgg tgaagtagca 14700 caaaaattaa ctgaagcaca agcacttaac caagcaatgg aagctttacg taatagcatt 14760 caagatcaac aacaaacaga atctggtagc aagtttatta atgaagataa accgcaaaaa 14820 gatgcttacc aagcagcagt tcaaaatgca aaagatttaa ttaaccaaac aggtaatcca 14880 acgcttgata aagcacaagt tgaacaattg acacatgctt ttaaacaagc taaagataac 14940 ctacacggtg atcaaaaact tgcagacgat aaacaacatg cggttactga tttaaatcaa 15000 ttaaatggtt tgaataatcc gcaacgtcaa gcacttgaaa gccaaataaa caacgcagca 15060 actcgtggcg aagtagcgca aaaattagct gaagcaaaag cgcttgatca agcaatgcaa 15120 gcattacgaa atagtattca agatcaacaa caaacggaag cgggtagcaa gtttatcaat 15180 gaagataaac cgcaaaaaga tgcttaccaa gcagcagttc aaaatgcaaa agatttaatt 15240 aaccaaacag gtaatccaac actcgacaaa tcacaagtag aacaattaac acaagcagta 15300 acaactgcaa aagataatct acatggtgat caaaaacttg ctcgtgatca acaacaagca 15360 gtaacaactg taaatgcatt gccaaactta aatcatgcac aacaacaaac attaactgat 15420 gctataaatg cagcgcctac aagaacagag gttgcacaac atgttcaaac tgctactgaa 15480 cttgatcacg cgatggaaac attgaaaaat aaagttgatc aagtgaatac agataaggct 15540 caaccaaatt acactgaagc gtcaactgat aaaaaagaag cagtagatca agcgttacaa 15600 gctgcacaaa gcattacaga tccaactaat ggttcaaatg cgaataaaga cgctgtagaa 15660 caagcattaa ctaagcttca agaaaaagtg aatgagttaa atggtaatga gagagtcgct 15720 gaagctaaaa cacaagcgaa acaaactatt gaccaattaa cacatttaaa tgctgatcaa 15780 attgcaactg ctaaacaaaa tattgatcaa gcgacgaaac ttcaaccaat cgctgaatta 15840 gtagatcaag caacgcaatt gaaccaatca atggatcaat tacaacaagc agttaatgaa 15900 catgctaacg ttgagcaaac tatagattac acacaagcag attcagataa gcaaaaggct 15960 tataaacaag cgattgctga tgctgaaaat gtattgaaac aaaatgcgaa taagcaacaa 16020 gtggatcaag cacttcaaaa tattttaaat gcaaaacaag cattaaatgg tgatgaacgt 16080 gtagcacttg ctaaaacaaa tggtaaacat gacatcgacc aattgaatgc attaaacaat 16140 gctcaacaag atggatttaa aggtcgcatc gatcaatcaa acgatttaaa tcaaatccaa 16200 caaattgtag atgaggctaa ggcacttaat cgtgcaatgg atcaattgtc acaagaaatc 16260 actggcaatg aaggacgcac gaaaggtagc acgaactatg tcaatgcaga tacacaagtc 16320 aaacaagtat atgatgaagc ggttgataaa gcgaaacaag cacttgataa atcgtctggg 16380 caaaacttaa ctgcagaaca agttatcaaa ttaaatgatg cagtcactgc agctaagaaa 16440 gcattaaatg gtgaagaaag acttaataat cgtaaagctg aagcattaca aagattggat 16500 caattaacac atctaaacaa tgctcaaaga caattagcaa tccaacaaat taataatgct 16560 gaaacgctaa ataaagcatc tcgagcaatt aatagagcaa ctaaattaga taatgcaatg 16620 ggtgcagtac aacaatatat tgacgaacag caccttggtg ttatcagcag cacaaattac 16680 atcaatgcag atgacaattt gaaagcaaat tatgataatg caattgcgaa tgcagcacat 16740 gagttagata aagtgcaagg taatgcaatt gcaaaagctg aagcagagca attgaaacaa 16800 aatattatcg atgctcaaaa tgcattaaat ggagaccaaa accttgcaaa tgccaaagat 16860 aaagcaaatg cgtttgttaa ttcgttaaat ggattaaatc aacagcaaca agatcttgca 16920 cataaagcaa ttaacaatgc cgatactgta tcagatgtaa cagatattgt taataatcaa 16980 attgacttaa atgatgcaat ggaaacattg aaacatttag ttgacaatga aattccaaat 17040 gcagagcaaa ctgtcaatta ccaaaacgct gacgataatg ctaaaacaaa cttcgatgat 17100 gccaaacgtc tagcaaatac attgctaaat agtgataaca caaatgtgaa tgatatcaat 17160 ggcgcaatcc aagcagtcaa tgatgcaatc cataatctta atggtgatca acgactacaa 17220 gatgctaaag acaaggcaat tcaatcaatt aatcaagctt tagctaataa gctaaaagaa 17280 atcgaagctt caaatgcgac ggatcaagac aagcttattg cgaaaaataa agcagaagaa 17340 ttggcaaaca gcatcatcaa caacattaat aaagcaacaa gtaatcaggc tgtatctcaa 17400 gttcaaacag caggcaacca cgcgattgaa caagtgcatg ctaatgaaat accaaaagca 17460 aaaattgatg ccaataaaga cgttgataag caagttcaag cattaattga cgaaattgat 17520 cgaaatccaa atctaacaga taaggaaaaa caagcactta aagatcgtat taatcaaata 17580 cttcaacaag gtcataacga cattaacaat gcgctgacta aagaagaaat tgaacaagct 17640 aaagcacaac ttgcgcaagc attacaagac atcaaagatt

tagtgaaagc taaagaagat 17700 gcgaaacaag atgttgataa acaagttcaa gcattaattg acgaaatcga tcaaaatcca 17760 aatctaacag ataaggaaaa acaagcactt aaagatcgta ttaatcaaat acttcaacaa 17820 ggtcataacg gcattaacaa tgcgatgact aaagaagaaa ttgaacaagc caaagcacaa 17880 cttgcacaag cattaaaaga aattaaagat ttagtgaaag ctaaagaaaa tgcgaaacaa 17940 gatgttgata aacaagttca agcattaatt gacgaaatcg atcaaaatcc aaatctaaca 18000 gataaggaaa aacaagcgct taaagatcga atcaatcaaa tactgcaaca aggtcataac 18060 gacattaaca atgcgatgac taaagaagaa attgaacaag ccaaagcaca acttgcacaa 18120 gcattacaag acatcaaaga tttagtgaaa gctaaagaag atgcgaaaaa tgcaataaaa 18180 gccttagcta atgcgaagcg tgatcaaatc aattcaaatc cagatttaac acctgagcaa 18240 aaagcaaaag cgctcaaaga aattgacgaa gctgaaaaac gagcactaca aaacgttgag 18300 aatgctcaaa ctatagatca attaaatcga ggattaaact taggtttaga tgacattaga 18360 aatacacatg tatgggaggt tgatgaacaa cctgctgtaa atgaaatttt tgaagcaaca 18420 cctgagcaaa tcctagttaa tggtgaactc attgtacatc gtgatgacat cattacagaa 18480 caagatattc ttgcacacat aaacttaatt gatcagcttt cagcagaagt tattgataca 18540 ccatcaactg caacgatttc tgatagctta acagcaaaag ttgaagttac attgcttgat 18600 ggatcaaaag tgattgttaa tgttcctgta aaagttgtag aaaaagaatt gtcagtagtc 18660 aaacaacagg caattgaatc aatcgaaaat gcggcacaac aaaagattga tgaaatcaat 18720 aatagtgtga cattaacact ggaacaaaaa gaagctgcaa ttgcagaagt taataagctt 18780 aaacaacaag caattgatca tgttaacaat gcacctgatg ttcattcagt tgaagaaatt 18840 caacaacaag aacaagcgta tattgaacaa tttaatccag aacaatttac gattgaacaa 18900 gcaaaatcaa atgcaattaa atcgattgaa gatgcaattc aacatatgat tgatgaaatc 18960 aaagctcgta ctgatctaac agataaagag aagcaagaag ctattgctaa gttaaatcaa 19020 ttaaaagaac aagcaattca agcgattcaa cgtgcgcaaa gcatcagtga aataactgag 19080 caattggaac aatttaaagc tcaaatgaaa gcagctaatc caacagcaaa agaactagct 19140 aaacgcaagc aagaagctat tagtagaatt aaagactttt caaatgaaaa aataaatagt 19200 attcgaaata gtgaaattgg cacagctgat gaaaaacaag cagcaatgaa tcaaattaac 19260 gaaattgtgc ttgaaacaat tagagatatt aataatgcgc atacattaca gcaagttgag 19320 gctgcattga acaatggtat tgctcgaatt tcagcagtac aaattgtaat atctgatcgt 19380 gctaaacaat cgtcaagtac tggaaatgaa tctaatagcc atttaacaat tggttatgga 19440 actgcaaatc atccatttaa cagttcgact attggacata aaaagaaact tgatgaagat 19500 gatgacattg atccacttca tatgcgtcac tttagtaata atttcggtaa tgttattaaa 19560 aacgctattg gtgtggtggg tatctctggc ttactagcta gtttctggtt cttcattgcc 19620 aaacgtcgtc gtaaagaaga tgaagaggaa gaattagaaa taagagataa taataaagat 19680 tcaataaaag agactttaga cgatacaaaa catttaccac ttttatttgc gaaacgtcgc 19740 agaaaagaag atgaagaaga tgttactgtt gaagaaaaag attcgctaaa taatggcgag 19800 tcactcgata aagttaaaca tacgccgttc ttcttaccaa aacgtcgtcg taaagaagat 19860 gaagaagatg tggaagttac aaatgaaaac acagatgaaa aagtgttgaa agataacgaa 19920 cattcaccac tcttattcgc aaaacgacgc aaagataaag aggaagatgt tgaaacaaca 19980 actagtattg aatctaaaga tgaggacgtt cctttattat tggctaaaaa gaaaaatcaa 20040 aaagataacc aatccaaaga caaaaagtca gcatcaaaaa atacttctaa aaaggtagca 20100 gctaaaaaga agaaaaagaa atctaagaaa aataaaaaa 20139 47 2103 DNA S. epidermidis 47 ttgaataatc gtgataaatt acaaaaattt agtattcgaa aatacgcaat tggaacattt 60 tctactgtga ttgcaacact tgtgttcatg ggtatcaata caaaccatgc aagtgccgac 120 gagttgaatc aaaatcaaaa gttaattaaa caattaaatc aaacagatga tgatgattcg 180 aatacgcata gtcaagaaat cgaaaataac aaacaaaatt ctagtgggca gactgaatca 240 ttacgttcat caactagtca aaatcaagca aatgcacgac tgtcggatca attcaaagac 300 actaatgaaa catcgcaaca attacctaca aatgtttcgg atgatagtat caatcaatcg 360 catagtgaag caaatatgaa taacgaacca ttgaaagttg ataatagtac tatgcaagca 420 catagtaaaa tagtaagcga tagcgatggg aatgcttctg aaaataaaca tcataaacta 480 acagaaaatg tacttgcaga aagccgagca agtaaaaatg acaaagagaa agagaatcta 540 caagagaaag ataaatcgca gcaagtacat ccaccattag ataaaaatgc attacaagct 600 ttttttgacg catcatatca caattacaga atgattgata gagatcgtgc ggatgcaaca 660 gaatatcaaa aagtcaaatc tacttttgac tacgtcaatg acttactagg taataatcaa 720 aatattcctt cagaacagct tgtttcggca tatcaacaat tagagaaagc attagaactt 780 gcacgtacgt taccacaaca atctactaca gaaaaacgtg gtagaagaag tacgagaagt 840 gttgttgaga atcgttcatc aagaagcgat tacttagatg ctagaactga atattatgtt 900 tcaaaagacg atgatgattc tggtttccct cctggtactt tcttccatgc ttcaaataga 960 agatggcctt ataatttacc aagatctagg aacatcttac gtgcttctga tgtacaaggt 1020 aatgcttata tcactacaaa acgacttaaa gatggatatc aatgggatat tttatttaat 1080 agtaatcata aagggcatga atatatgtac tattggtttg gacttccaag tgatcaaaca 1140 ccaactggtc cagtaacttt cactattatc aaccgtgatg gttcaagtac atctactggt 1200 ggcgttggat ttggatcagg tgcaccacta cctcaatttt ggagatcagc aggtgctatt 1260 aattctagcg tagcgaatga ttttaaacat ggctccgcta caaattatgc attttatgat 1320 ggtgttaata atttttctga ctttgctaga gggggagaat tatacttcga cagagaaggc 1380 gctacacaaa ctaataaata ttatggcgat gaaaacttcg cattgctaaa tagtgagaaa 1440 ccagatcaaa taagaggatt agatacaata tatagtttta aaggtagtgg tgatgtaagt 1500 tatcgtattt catttaaaac tcaaggagct ccaactgcaa gattgtatta tgctgctggc 1560 gcgcgttctg gtgaatataa acaagcaacg aactataacc aactctatgt cgaaccttat 1620 aagaattatc gaaatcgagt acagtcaaat gtccaagtta aaaatcgtac acttcattta 1680 aaaagaacaa tcagacaatt cgatcctaca ttacagagaa ctactgatgt tcctattttg 1740 gatagtgacg gttccggaag tattgattcg gtatacgacc cattaagtta tgtaaagaat 1800 gtgactggta cagtcctagg tatttatcca tcttatcttc cttataatca ggaaagatgg 1860 cagggagcta atgcaatgaa tgcctatcaa attgaagaac ttttttcaca agaaaatctt 1920 caaaatgcag cacgttcagg ccgtccaatt caatttcttg taggttttga tgttgaagat 1980 agccatcata accctgaaac tcttttacca gtaaatttat atgtaaaacc tgagttaaaa 2040 catacaattg agttatatca cgataatgaa aaacaagata gaaaggaatt ttcagtatcg 2100 aa 2103 48 28317 DNA S. epidermidis 48 atgagtggaa cgcttcataa cactgtagga tcaggaatat taccttatca acaagagata 60 cgtatcaaac ttactagtaa tgaaccaatt aaagatagtg aatggtctat tacaggatat 120 cctaacacgc ttacattaca aaacgctgtg ggtagaacaa ataatgctac tgaaaaaaac 180 ttagctcttg ttggtcatat tgatccagga aattatttca tcactgttaa gtttggtgat 240 aaagtagaac aatttgaaat tagatcaaaa ccaactccac caagaatcat tacaactgct 300 aatgaattac gtggaaatcc taaccataag cctgaaataa gagtaacaga tataccaaat 360 gatactactg ctaaaatcaa acttgtgatg ggcggaaccg atggcgatca tgatccagaa 420 ataaatccat atactgtccc tgaaaactac acagtagttg cagaagcata ccatgataat 480 gatccaagta aaaatggggt cttaacattc cgttcatcag actaccttaa agatctacca 540 ttaagcggtg aattaaaggc aattgtttat tacaatcaat atgtacaatc aaactttagt 600 aaaagcgttc cgtttagtag cgatacaaca ccacctacaa ttaatgaacc ggcaggacta 660 gttcataagt attacagggg agatcatgta gaaattactc ttccagtcac tgataatact 720 ggcggttcag gtttaagaga tgtaaacgtc aatttacctc aaggttggac aaaaaccttt 780 acaatcaatc ctaataataa tactgagggt acgcttaagt taattggtaa tatacctagt 840 aatgaagcat ataatacgac atatcatttc aatattactg caaccgataa ttctggaaat 900 acaacaaatc cagctaaaac ctttatttta aatgttggta agttggctga tgatttaaat 960 ccagtcggat tatctagaga tcaactacaa ttagtgacag acccttcttc attatctaat 1020 tccgaacgag aagaggtaaa aagaaaaata agtgaagcaa atgctaatat aagatcatat 1080 ttattacaaa ataacccaat actcgctgga gtaaacggcg atgttacatt ttattataga 1140 gatggttctg tagatgttat tgatgctgaa aatgtaatca catatgagcc cgaaagaaaa 1200 tccattttca gtgaaaatgg taatacaaat aaaaaagaag cagtaatcac tattgctaga 1260 ggacaaaact ataccattgg tccaaactta agaaaatatt tctcattaag taatggttcg 1320 gatttaccta atagagattt cacctctata tcagctattg gatctttacc ttcatcgagt 1380 gaaattagtc gactcaatgt tggaaattat aactatagag ttaatgctaa aaatgcttat 1440 cataagactc aacaagaact taatttaaaa cttaaaatag tagaggttaa tgcacctact 1500 ggtaataatc gtgtatatag agttagtact tataatttaa ctaatgatga aatcaataaa 1560 atcaaacaag catttaaagc agctaattct ggacttaatt taaacgataa cgatatcact 1620 gtttcgaata actttgacca tagaaatgtt agtagtgtga cagtaactat acgtaagggc 1680 gatttgataa aagagttttc atcaaatctc aataatatga atttcttacg ttgggttaat 1740 ataagggatg attataccat ttcgtggact tctagtaaga ttcaaggtag aaatacagat 1800 ggtggattag aatggtcacc agatcataaa tcacttattt ataaatatga tgcaacatta 1860 ggtagacaaa taaatactaa tgacgtgtta actttacttc aagcaacagc taaaaactca 1920 aatttacgtt caaatatcaa tagtaatgaa aaacagttag cagaacgagg gtctaatggg 1980 tattctaaat ctataattag agatgatggc gagaaatctt atttacttaa ctcaaatcct 2040 attcaagtat tagacttagt agaaccagat aatggttacg gtggacgtca agtcagtcat 2100 tctaacgtta tatataatga aaaaaattct tctatcgtaa atggtcaagt tccagaagct 2160 aatggggcat ccgcttttaa tattgataaa gttgttaaag ctaatgcggc aaataatggt 2220 attatgggtg ttatctataa ggcacaatta tacttagcac catacagtcc aaaaggttac 2280 attgaaaaat taggccaaaa tttaagcaat accaataacg tgattaatgt ttattttgtg 2340 ccttctgata aagtaaatcc tagtataact gtaggtaatt acgaccatca tacggtatat 2400 tctggtgaaa catttaaaaa tactatcaat gtaaatgata attatggatt aaatacagta 2460 gcttctacaa gtgatagtgc aattactatg accagaaaca acaacgagtt agtaggtcag 2520 gctcctaatg ttactaatag cataaataaa attgtaaaag ttaaagccac agataaaagt 2580 ggaaatgaaa gtattgtttc tttcacagta aatataaaac cattaaacga gaaatataga 2640 ataacaactt catcaagtaa tcaaacacca gtgagaatta gtaatattca aaacaatgct 2700 aacctttcaa ttgaagatca aaatagagta aaatcttcac tcagcatgac taaaatttta 2760 ggtacaagaa attatgtcaa tgagtcaaat aatgacgttc gtagtcaagt tgtaagtaaa 2820 gtaaatagaa gtgggaacaa tgctacagtt aatgttacaa ctacattttc tgatggtaca 2880 actaatacaa taaccgttcc agttaaacat gtgttattag aagttgtacc tactactaga 2940 acaacagtaa gaggacaaca atttccaacc ggcaaaggaa cttccccaaa tgatttcttt 3000 agtttaagaa cgggaggtcc agttgatgcg agaatagttt gggttaataa tcagggaccc 3060 gatataaata gtaatcaaat tggtagagat ttaacattac acgctgaaat attctttgat 3120 ggtgaaacaa caccaattag aaaagatact acttacaaac ttagtcaatc tattccaaag 3180 caaatatatg aaacaactat caatggtcga tttaattcat caggtgatgc atatccagga 3240 aattttgttc aagcagtaaa tcaatattgg ccagaacata tggacttcag atgggcccaa 3300 ggatcaggca caccaagttc tcgtaatgca ggttcattta ctaaaacagt tacggtagtt 3360 tatcaaaacg gccaaactga aaacgttaat gtactattca aagtcaaacc aaataaacct 3420 gttattgata gtaatagtgt gatttcaaaa ggacaattaa atggtcaaca aattttagtt 3480 cgaaatgttc cacaaaatgc acaagtcact ctatatcaat caaatggaac tgttattcct 3540 aatacaaata caactataga ttctaatggt atagctactg taacaattca aggcactcta 3600 ccaaccggaa atattactgc taaaacctca atgacaaata atgtaacgta cactaaacaa 3660 aatagtagtg gaattgcttc aaatacaact gaagatataa gtgttttttc agaaaacagt 3720 gatcaagtaa atgttaccgc tggcatgcaa gctaaaaatg atggtattaa aataattaaa 3780 ggtacaaact ataattttaa tgacttcaat agtttcataa gtaatatacc agcccattct 3840 actcttacat ggaacgagga gcctaatagt tggaaaaaca acatcggtac tacaacaaaa 3900 actgttacag ttactctacc taatcatcaa ggtacgagaa ctgtagatat tccaataaca 3960 atctatccaa cagttacagc taagaatcca gtaagagatc aaaaaggacg aaacttaacc 4020 aatggtactg acgtttataa ttatattatt tttgaaaata ataaccgtct tggaggaaca 4080 gcttcttgga aagacaatcg tcaacctgat aaaaacatag ccggtgtaca aaatttaatt 4140 gcacttgtta attatcctgg catatctaca ccattagaag ttcctgttaa agtgtgggta 4200 tataattttg atttcactca acctatctac aaaattcaag taggagatac attccctaaa 4260 ggaacatggg caggctatta caaacatctt gaaaatggag agggattacc aatagatggt 4320 tggaaatttt attggaacca gcaaagtaca ggaactacta gtgatcaatg gcaatcatta 4380 gcatatacta gaactccttt tgttaaaact ggtacttatg atgtcgttaa tcctagcaac 4440 tggggtgttt ggcaaacatc acaatcagct aaatttatag ttacaaatgc taaacctaat 4500 caaccaacca taactcagtc taaaactggt gatgtaacag taacacctgg tgctgtgcgt 4560 aatatactaa taagtgggac aaatgattat atccaagcat ctgcagataa gattgttatt 4620 aataaaaatg gaaataaatt aactacattt gttaaaaata atgatggtcg ttggactgtt 4680 gaaactgggt cacctgacat aaatggtatc ggaccaacaa ataacggaac tgctatatct 4740 ttaagtcgat tagcagttag acctggggat tcaatagaag caatagcgac tgaaggttcc 4800 ggagaaacta taagtacttc agcaactagt gaaatttata ttgtcaaagc tccacaacct 4860 gaacaagtag caactcatac ttatgataat ggaacattcg atatattacc tgacaattca 4920 cgtaattctt taaatccaac tgaacgtgtc gaaattaatt acactgaaaa attaaatggc 4980 aatgaaacac aaaaatcatt cactattact aaaaataaca acggcaaatg gacgataaat 5040 aataaaccaa attatgtcga gttcaatcag gataatggta aagttgtatt ttcggccaat 5100 acaattaaac ctaattctca aattacaata actcctaaag caggtcaggg taacactgaa 5160 aacacaaatc ctactgtaat tcaagcacct gcgcaacata ctttaacaat caatgaaatt 5220 gttaaagaac agggtcaaaa tgtgactaat gatgatatta ataatgcggt tcaagtgcca 5280 aataaaaata gagttgcgat taaacaagga aacgctcttc caacaaattt agctggtggt 5340 agtacatcac atattccagt agttatttat tacagtgatg gaagttctga agaagctact 5400 gagactgtta gaactaaagt taataaaacc gaattaatca atgctcgtcg tcgactagat 5460 gaagaaatta gtaaagagaa caaaacacca tcaagtatca gaaactttga tcaagctatg 5520 aatcgtgctc aatcacaaat taatacagct aaaagtgatg ctgaccaagt tataggcaca 5580 gaatttgcaa cacctcaaca agtaaattca gctttatcta aagttcaagc ggcacaaaat 5640 aaaataaatg aagctaaagc attattacaa aacaaggctg ataatagtca acttgtgaga 5700 gcaaaagaac aattacaaca atcgattcaa ccagccgctt caactgatgg tatgactcaa 5760 gatagcacaa ggaactacaa caataaacgc caagcagctg aacaagcaat acaacatgca 5820 aatagcgtta taaataatgg agatgcaaca tcccaacaaa ttaatgatgc taaaaacaca 5880 gttgaacagg cacagagaga ttatgttgaa gctaaaagca acttacgtgc tgataagtca 5940 cagttacaaa gcgcttatga tacgttaaat agagatgttt taacaaatga taaaaagcca 6000 gcatctgtaa gacgctataa tgaagccatt tcaaatatta gaaaagaatt agatacagct 6060 aaagcggatg caagtagtac tttgcgaaac accaatcctt ccgttgaaca agttagagac 6120 gctttaaata aaataaatac tgttcaacct aaagtgaatc aagcaattgc tttacttcaa 6180 ccaaaagaaa ataattcaga acttgtacaa gctaaaaaac gtttacaaga cgctgtaaat 6240 gacatacctc aaacacaagg tatgacacaa caaacaatta ataattataa tgacaaacaa 6300 cgtgaagctg aaagagcact tacatctgca caaagagtga ttgataatgg ggatgctaca 6360 actcaagaaa ttacttctga aaaatctaaa gtagagcaag caatgcaagc tttaactaat 6420 gctaaaagta atctgagagc tgataagaat gagttacaga ctgcatataa caaattaatt 6480 gagaacgtat ctaccaatgg taaaaaaccg gcgagtatac gtcaatacga aacagccaaa 6540 gccagaatac aaaatcaaat taatgatgct aaaaatgaag cggagcgaat tttaggtaat 6600 gataatccac aagtatcaca agtaactcaa gcattgaaca aaatcaaagc tattcaacca 6660 aaattaacag aagctatcaa catgcttcaa aacaaagaaa ataatacaga attagtcaat 6720 gctaaaaaca gacttgaaaa tgcagtaaat gatacagatc caacacacgg tatgactcaa 6780 gaaacaatta ataattacaa cgctaaaaag cgagaagctc aaaatgaaat acaaaaagcg 6840 aacatgatta ttaataatgg agatgctact gctcaagata tttcttctga aaaatctaaa 6900 gtagagcaag tattacaagc attacaaaat gctaagaatg acttaagagc tgataaaaga 6960 gaattacaga ctgcatacaa taaacttata caaaatgtta ataccaatgg taaaaaacca 7020 tctagtattc aaaactataa gtctgcaaga cgaaatatcg aaaaccaata taataccgct 7080 aaaaatgaag cacataatgt tcttgaaaat acaaacccta ctgtaaatgc agtagaagat 7140 gctttacgta agataaatgc aattcaacca gaggttacaa aagctattaa tatacttcaa 7200 gataaagaag ataatagcga acttgttaga gcaaaagaaa aattagatca agcgattaat 7260 agtcaaccat cactaaatgg tatgactcaa gaatctatta ataattacac aacaaaacgt 7320 agagaagcac aaaatatagc aagttctgct gacactatta ttaataatgg ggatgcatct 7380 attgaacaaa taacagaaaa taaaattcga gttgaagagg caactaatgc acttaacgaa 7440 gcaaaacaac atttaacggc agatacaact tctttaaaaa ctgaagtacg gaaattaagt 7500 aggagaggcg acacaaacaa caaaaagcct agcagtgtta gtgcttataa caatactatt 7560 cattcgctac aatctgaaat tacacagact gaaaatagag caaatactat catcaataag 7620 cctattcgtt ctgttgaaga agtaaataat gcattgcatg aagtaaacca attgaaccaa 7680 cgcttaacag atacaattaa cttattacaa cctttagcga ataaagaaag cttaaaagaa 7740 gctcgtaatc gacttgaaag taaaattaat gaaaccgttc aaacagacgg tatgactcaa 7800 caatctgttg agaattataa gcaagctaaa ataaaagctc aaaatgaatc tagtattgca 7860 caaactctta ttaataatgg tgatgcatct gatcaagaag tttctacaga aatagaaaaa 7920 ttaaatcaaa agctgtctga attaacaaat tcaatcaatc acttaacagt taataaagaa 7980 cctttagaaa ctgccaaaaa tcagttacaa gcaaatattg accaaaaacc tagcactgat 8040 ggtatgacgc aacaatctgt acaaagctat gaacgtaaac tacaagaagc caaagataaa 8100 ataaactcaa ttaataatgt cttagctaac aatccagatg ttaatgctat cagaacaaac 8160 aaagttgaga cggaacaaat caataatgaa ttaacacagg cgaaacaagg tcttactgtt 8220 gataaacaac cattgattaa tgcaaaaact gctttgcaac aaagtctaga taatcaacca 8280 agtactactg gtatgactga agcaacaatt caaaattata acgctaaacg tcaaaaagca 8340 gagcaagtta tacaaaatgc aaataaaatt attgaaaacg ctcaacctag tgtacaacaa 8400 gtgtctgatg agaaatctaa ggtagagcaa gcactcagtg aattgaacaa cgccaaatca 8460 gcgcttagag ctgataaaca agaattacag caagcatata atcagttgat tcaaccaacg 8520 gatttaaata ataagaaacc agcttctatc actgcgtaca atcaaagata tcaacaattt 8580 agtaacgaat tgaacagcac taaaacaaat acagatcgca ttttaaaaga gcaaaatcca 8640 agtgtagctg atgtcaacaa tgcactaaat aaagtaagag aagtacaaca aaaattaaac 8700 gaagccagag cacttttaca aaataaagaa gataatagtg cactagttcg agccaaagaa 8760 caacttcaac aggcagttga ccaagtccct tcaacagaag gtatgacgca acaaactaaa 8820 gatgattaca attcaaaaca acaagctgct caacaagaaa tatcaaaagc acaacaagtt 8880 atcgataatg gcgatgcgac tacacaacaa atttctaacg ccaaaacaaa tgttgaacgc 8940 gctttagaag cattaaataa tgcaaaaact ggtttaagag cagataaaga ggaacttcaa 9000 aatgcatata atcaattaac tcaaaatatt gatacgagcg gtaaaacgcc tgcaagtatc 9060 aggaaataca atgaagctaa gtcacgtatt caaactcaaa ttgattcagc taaaaatgaa 9120 gcaaacagta ttttaacaaa tgacaatcct caagtatcac aagtgactgc tgcgttaaac 9180 aaaataaaag ctgttcaacc tgaattagat aaagcgatag caatgcttaa aaataaagag 9240 aataataatg cattggttca agcgaaacaa caacttcaac aaattgttaa tgaagtagat 9300 ccaacacaag gcatgacaac agatactgct aataactata aatcaaaaaa acgtgaagct 9360 gaagatgaaa tacaaaaagc tcaacaaatc attaacaatg gcgatgccac tgagcaacaa 9420 attactaacg aaacaaatag agtaaatcaa gcgattaatg caataaacaa agccaaaaac 9480 gatttacgtg ctgataagtc tcaattggaa aatgcttata accaattaat acaaaatgtt 9540 gatacaaatg gtaaaaaacc tgctagtatt caacaatacc aagctgctcg acaagctatt 9600 gagacgcaat acaataacgc taaatcagaa gcacatcaaa ttcttgaaaa tagtaaccct 9660 tcagttaatg aagtagcaca agcattacaa aaagttgaag ctgtacaact taaagttaat 9720 gacgcgattc atatacttca aaataaagag aataatagtg cacttgtcac agctaaaaat 9780 caacttcagc aatcagttaa tgatcaacca ttaacaacag gtatgactca agattctatt 9840 aataactatg aagctaagag aaatgaggct caaagtgcta tcagaaatgc agaagctgtc 9900 atcaacaatg gcgatgcaac tgcaaaacaa atttcagacg agaaatctaa agttgaacaa 9960 gcactagcac atttgaatga tgctaaacag caattaactg cagatactac tgaattacaa 10020 acagcagttc aacaattaaa cagaagaggc gatacaaata ataaaaagcc aagaagtatc 10080 aatgcatata ataaagcaat tcaatcatta gaaacacaaa ttacttctgc taaagataat 10140 gccaacgctg tgatacaaaa acctatacgt actgttcaag aggtaaataa tgcattacaa 10200 caagtaaatc agttgaatca acaattaact gaagcaatta atcaacttca accgctatca 10260 aataatgatg cattaaaagc tgcaagatta aatttagaaa ataaaattaa tcaaactgta 10320 caaactgatg gtatgacaca acaatctata gaggcttatc aaaacgctaa

acgcgtagcc 10380 caaaatgaat ctaacactgc tttagcatta attaataacg gcgatgccga tgaacaacaa 10440 attacaactg aaacagaccg agtcaatcag caaactacaa acttaactca agcaattaac 10500 gggttaacag ttaataaaga accattagaa accgctaaaa cagcgttaca aaataacatc 10560 gaccaggtac ctagtacaga tggtatgact cagcaatctg ttgcaaatta taatcaaaaa 10620 ctacaaatag ctaaaaacga aattaacaca attaataacg ttttagcgaa caatccagat 10680 gttaatgcaa tcaaaacgaa taaagcagaa gcggaacgaa tcagtaacga tttaacacaa 10740 gctaagaata acttacaagt tgatactcaa cctttagaaa aaataaaaag acaacttcaa 10800 gatgaaattg atcaaggtac taacacagat ggaatgactc aagattcagt ggataattac 10860 aatgatagct taagtgcagc aattatagaa aaaggcaaag taaataaatt acttaaacgt 10920 aatccgacag tagaacaagt taaagagagc gttgctaatg cacaacaagt catacaagat 10980 ttacaaaatg ctcgaacttc acttgttcca gacaaaactc aacttcaaga agctaaaaat 11040 agattagaaa acagtattaa ccaacaaaca gatactgacg gcatgactca agattcgctt 11100 aacaattata atgataaatt agcaaaagct agacaaaacc ttgaaaaaat atctaaagtt 11160 ttaggtggtc aacctactgt agctgaaatt agacaaaata cagatgaagc aaatgcacat 11220 aaacaagcat tagacactgc acgttctcaa cttacattaa atagagagcc atatatcaat 11280 catattaata atgaaagtca tttaaataac gcgcaaaaag ataattttaa agctcaagtt 11340 aactcagcac ctaatcataa tactttagaa acgattaaaa ataaggctga tactttaaat 11400 caatctatga cagcattaag tgaaagtatt gcagattacg aaaatcaaaa acaacaagaa 11460 aattatttag atgcatctaa caataaacgt caagactatg acaatgcagt caatgcggct 11520 aaaggtattt taaaccaaac tcaaagtccg acaatgagtg ctgatgtgat tgatcaaaaa 11580 gctgaagatg ttaaacgtac gaaaactgcg ttagatggaa atcaaagatt agaagttgct 11640 aaacaacaag cacttaatca tttaaatacc ttaaatgatt taaacgatgc tcagcgacaa 11700 actttaactg atactataaa tcactctcca aacatcaatt cagtgaatca agctaaagaa 11760 aaagctaata ctgttaacac agcaatgact caactgaaac aaactattgc taactatgac 11820 gatgaattgc atgacggcaa ttacattaat gcagataaag acaaaaaaga tgcttataat 11880 aacgctgtta acaatgctaa acaactgatt aatcaatctg atgctaatca agcacaactt 11940 gatccagctg aaattaataa agttacacaa agagtcaata cgactaaaaa tgatctaaat 12000 ggtaatgaca aattggctga agctaaaaga gatgctaata caaccattga tggtttaact 12060 tatctaaatg aagctcaacg taacaaagct aaagaaaatg taggcaaagc ttctacaaaa 12120 acaaatatta cgagtcagtt acaagattac aatcaattga atattgctat gcaagcatta 12180 cgtaacagtg tgaacgacgt taacaatgtt aaagcaaata gcaattatat aaatgaagat 12240 aatggtccaa aagaagctta caatcaagcc gttactcatg ctcaaacatt gataaatgca 12300 caatctaacc ctgaaatgag ccgtgacgta gtaaatcaaa aaacacaagc agtaaatact 12360 gcccatcaga atttacatgg acaacaaaag ttagaacaag cacaaagtag tgctaataca 12420 gaaatcggta acttaccaaa cttaactaat actcaaaaag ctaaagaaaa ggaactggta 12480 aatagtaaac aaactcgtac ggaagtacaa gaacaactta accaagctaa gtcactagat 12540 agttctatgg gcacgttaaa atcattagtt gctaaacaac ctacagtaca aaaaacaagt 12600 gtttatatta acgaagatca acctgagcaa tctgcctaca atgattccat tacaatggga 12660 caaactataa ttaataaaac agctgatcca gtacttgata aaactttagt tgataacgca 12720 atcagtaaca tttcaactaa agagaatgca ctgcatggtg aacaaaaatt aacaactgct 12780 aaaacggaag caattaatgc acttaataca ttagctgatt taaacacacc tcagaaagag 12840 gctattaaaa cagctattaa cactgctcat acaagaactg atgtaactgc agagcaaagt 12900 aaggctaatc aaataaatag tgcaatgcac acgttgagac aaaacatttc tgacaacgaa 12960 tcagtaacaa acgaaagtaa ttatattaac gctgaacccg aaaaacaaca tgcctttact 13020 gaggctctaa ataatgctaa agaaatagtt aatgaacaac aagccactct tgatgccaat 13080 tcaattaacc aaaaagcaca agcgattctt actactaaaa atgctttaga tggtgaagaa 13140 caattacgtc gtgctaaaga aaatgccgat caagaaatca atacgttaaa tcaattgact 13200 gatgcgcaaa gaaatagtga aaaaggttta gtcaacagtt ctcaaactag aacagaagtt 13260 gcttctcaat tagcaaaagc taaagaacta aataaggtga tggaacaact gaatcacctt 13320 atcaatggta aaaaccaaat gataaatagc agtaaattta tcaatgaaga tgcgaaccaa 13380 caacaagcat attcaaatgc gattgcaagt gcagaagcgc ttaaaaacaa atcacaaaac 13440 cctgaattag ataaagtaac aattgaacaa gcaattaata atattaattc tgcaattaac 13500 aatctaaacg gtgaagctaa actgactaaa gctaaagaag atgctgttgc ttcaataaac 13560 aacctaagcg gattaacaaa cgagcaaaaa acaaaagaaa atcaagccgt taatggcgct 13620 caaactagag accaagttgc taataaatta cgtgatgctg aagcattaga tcaatcaatg 13680 caaacattac gtgacttagt taacaatcaa aatgcaatac attcaacaag taattatttt 13740 aacgaggatt caactcaaaa gaatacttat gataatgcaa ttgataatgg ctcgacatat 13800 ataactggtc aacacaatcc agaattaaat aaatctacta ttgatcaaac gattagccga 13860 attaacacag ctaaaaatga tttacatggt gtagaaaagt tacaaagaga taagggaact 13920 gctaatcaag aaattggaca attaggttat ttaaatgacc ctcaaaaatc tggtgaggaa 13980 tccttagtca acggttcaaa tacacgttct gaagtagaag agcatcttaa tgaagctaaa 14040 tcattaaata atgcaatgaa acaattaaga gataaagtag ctgaaaagac taatgtcaaa 14100 caaagtagcg attacattaa tgattcaact gaacatcaac gtgggtatga tcaagcactt 14160 caagaagcag aaaatattat taatgaaatc ggtaatccaa cattaaataa atcggaaatt 14220 gaacaaaagt tacaacaatt gactgacgct caaaatgcgt tacaaggttc acatctatta 14280 gaagaagcta aaaataatgc gattactgga atcaataaac ttacagcatt aaatgatgca 14340 caacgtcaaa aagcaattga aaatgttcaa gcacagcaga caatcccagc agttaatcaa 14400 caattaactt tggatagaga aataaatact gcaatgcaag ctttacgaga taaagtaggc 14460 caacaaaata acgttcacca acaaagtaat tatttcaatg aagatgaaca accaaaacat 14520 aactatgata attctgtaca agccggtcaa actattattg ataaacttca agatccaatc 14580 atgaacaaaa atgaaattga gcaggctatt aatcaaatca atacgactca aacagcgtta 14640 agtggagaaa ataaattaca cactgaccaa gaaagcacaa atagacaaat agaaggttta 14700 tctagtttga acacagctca aatcaacgcc gaaaaagatt tagtcaatca agctaaaaca 14760 agaacagatg ttgctcaaaa gttagctgca gctaaagaaa taaattctgc tatgagtaat 14820 ttaagagatg gcattcaaaa taaagaggac atcaaacgta gcagtgcata tatcaacgca 14880 gatccgacta aagttacagc ttacgatcaa gcactacaga acgcagaaaa tatcatcaat 14940 gccacaccaa acgtagagct taataaagct acaattgaac aagcgctatc acgcgttcaa 15000 caagcacaac aagatcttga tggtgttcaa caattagcta atgctaaaca acaagctaca 15060 caaactgtca atgggttaaa tagcttaaat gacggtcaaa agcgtgaatt aaatctatta 15120 attaattcag ctaatacccg tacaaaagta caagaagaat taaacaaagc aactgaattg 15180 aaccatgcga tggaagcttt aagaaacagt gttcaaaacg ttgatcaagt aaaacaaagt 15240 agcaattatg tcaatgaaga tcaacctgaa cagcacaatt atgataatgc tgtcaatgaa 15300 gctcaagcta caatcaacaa caatgctcaa cctgttctag acaaattagc tatagaacgt 15360 ttaactcaaa ctgttaacac tacaaaagat gcattacatg gtgctcaaaa actgacacaa 15420 gaccaacaag ctgctgaaac tggaatacgt ggtttaacga gtctcaatga acctcagaaa 15480 aatgctgaag tagctaaagt aactgcagca acaacacgtg atgaagtgag aaatattcgt 15540 caagaagcaa caacattaga tactgcaatg cttggtttac gtaaaagcat taaagataaa 15600 aacgatacta aaaatagtag taaatatatt aatgaggatc atgaccaaca acaagcttat 15660 gacaatgctg taaataatgc tcaacaagtt atcgatgaaa ctcaagcaac gttaagctca 15720 gatacaatca atcaattggc aaatgccgta actcaagcta aatctaatct tcatggagat 15780 actaaactac aacacgataa agatagtgct aaacaaacga ttgctcaatt acagaatttg 15840 aattcagctc aaaaacatat ggaagattct ttaattgata atgaatctac acgtacgcaa 15900 gtccaacacg atttaacaga agctcaagct ttagatggtt taatgggtgc cttaaaagaa 15960 agtattaaag attatactaa tattgtttca aacggtaatt acatcaatgc ggaaccatct 16020 aagaaacaag catatgatgc agctgtacaa aatgctcaaa atataataaa tggaacgaat 16080 caaccaacaa ttaataaagg taatgtcact acagcaacac aaaccgtgaa aaatactaaa 16140 gatgccttag acggtgatca tagattagag gaagctaaaa ataatgccaa tcaaacaatc 16200 agaaatctat ctaatttgaa caatgcccaa aaagatgcag agaaaaatct agttaatagc 16260 gcatcaacat tagaacaagt tcaacaaaac ttacaaaccg ctcaacaatt agataatgct 16320 atgggtgagt tacgacaaag tattgctaaa aaagatcaag tgaaagcaga tagtaaatat 16380 ctaaatgaag atcctcaaat taagcaaaac tatgatgatg cagttcaacg tgttgaaact 16440 attattaacg aaactcaaaa ccctgaatta cttaaagcaa acattgacca agcaactcaa 16500 tccgttcaaa atgcagaaca agctttacat ggtgctgaaa aattaaatca agacaaacaa 16560 acgtcttcga cagaactaga tggattaaca gatttaacag atgcacaacg tgaaaaactc 16620 agagaacaaa ttaacacttc taatagtaga gatgatatta agcaaaaaat tgagcaagca 16680 aaagcactaa atgacgcaat gaaaaaactt aaagaacaag ttgcgcaaaa agatggtgtt 16740 catgctaaca gtgattatac aaatgaagat tctgcacaaa aagatgcgta taataatgca 16800 cttaaacaag cggaagacat tattaataac agctcaaatc ctaacttaaa tgcacaagac 16860 attactaatg ctttaaataa tattaaacaa gcacaagata accttcatgg agctcaaaaa 16920 ttacagcaag acaaaaatac aactaatcaa gccattggta acttaaatca tcttaatcaa 16980 cctcaaaaag atgcgcttat acaagctatt aatggagcta catctaggga ccaagttgca 17040 gaaaaactta aagaggccga agcgcttgat gaagctatga aacaacttga agatcaagtg 17100 aatcaagatg atcaaatttc aaatagcagc ccattcataa atgaagactc agacaaacaa 17160 aaaacttata atgataaaat ccaagctgca aaagaaataa ttaatcaaac atctaatcca 17220 accttagata aacaaaaaat tgctgataca cttcaaaata ttaaagatgc agtgaataat 17280 ttacatggtg atcaaaaatt agctcaatct aaacaagatg ctaataatca attaaatcat 17340 ttagatgact taaccgaaga acaaaaaaac cattttaaac cgttaattaa taatgctgat 17400 actcgagatg aggtaaataa acaactagag attgctaaac aattaaatgg tgatatgagt 17460 acacttcata aagtcataaa tgataaagat caaattcaac atttaagcaa ttacattaat 17520 gctgataatg ataaaaaaca aaattatgat aatgctatta aagaagctga ggatttaatt 17580 cataatcatc cagatacatt agatcataaa gcattacaag atttattaaa caagatagac 17640 caagcgcata acgaattaaa tggagaatcc agatttaaac aggctttaga caatgcttta 17700 aacgacatag atagcttaaa cagtctcaat gttccacaac gccaaactgt taaggataac 17760 atcaaccatg tgacaactct agaaagttta gctcaagaat tgcagaaagc aaaagagctt 17820 aatgatgcta tgaaagcaat gagagatagc attatgaatc aagagcaaat tcgtaaaaat 17880 agcaattata ctaatgaaga cttagctcaa caaaatgcct ataatcatgc agtagataaa 17940 ataaataaca ttattggtga agacaatgcg acgatggatc ctcaaataat caaacaagca 18000 actcaagata taaatacagc tataaatgga ttaaatggag atcaaaaact tcaagatgca 18060 aagacagatg ctaaacaaca aattactaac tttactggtt taactgaacc acaaaaacaa 18120 gcattggaaa acatcattaa ccaacaaaca agcagagcaa atgttgctaa acagttaagt 18180 catgctaaat tcttaaatgg aaaaatggaa gaattaaaag ttgcagtagc caaagcgtca 18240 ttagtaagac aaaatagtaa ctatattaat gaagatgtct ctgaaaaaga agcatatgaa 18300 caagctatcg caaaaggtca ggaaataatt aattcagaaa ataatccaac aataagtagt 18360 actgatatca atcgtaccat tcaagaaatt aatgatgctg aacaaaatct tcatggtgat 18420 aataaattaa gacaagcaca ggaaattgca aagaatgaaa tacaaaatct agacggatta 18480 aattcagctc aaataacaaa attaatccaa gatataggca gaacaacaac taaacctgca 18540 gtaactcaga aactagaaga agcaaaagca ataaaccaag ctatgcaaca acttaaacaa 18600 agtatagccg ataaggatgc tactctaaat tctagtaact atctcaatga agattctgag 18660 aaaaagttag cgtacgataa tgctgtaagc caagctgaac aactcataaa tcaacttaac 18720 gacccaacta tggatataag taatattcaa gctattactc aaaaggtcat tcaagcaaaa 18780 gattcattgc acggtgcgaa taaacttgca caaaatcaag cagattcaaa tttaataata 18840 aatcaatcaa caaatttaaa tgataaacaa aagcaagcat taaatgactt aattaatcat 18900 gctcaaacta aacagcaagt ggcagaaata attgcacaag ctaataagtt aaataacgaa 18960 atgggcacac taaaaacact cgtagaagaa cagtcaaacg ttcatcaaca aagtaaatat 19020 attaatgaag atccgcaagt tcaaaatatt tataatgact ccattcaaaa aggtcgagaa 19080 atattaaacg gcactacaga tgatgtttta aacaacaata aaatagcaga tgccattcaa 19140 aacattcatt taactaaaaa cgatttacat ggtgatcaaa aattacaaaa agcacaacaa 19200 gatgcaacca atgaattaaa ctatttaaca aatctaaaca attctcaaag acaaagcgag 19260 catgatgaga ttaactctgc tccttcaaga actgaagttt ctaatgattt aaatcatgct 19320 aaagcactta atgaagctat gcgtcaactt gagaatgaag ttgctcttga aaacagtgtt 19380 aaaaaattaa gcgactttat caatgaagat gaagcggcac aaaatgaata tagtaatgca 19440 cttcaaaaag ctaaagacat tatcaacggc gttccaagta gcactttaga taaagctaca 19500 attgaagatg ctttattaga attgcaaaat gctagagaaa gtttacatgg tgagcaaaaa 19560 cttcaagagg ctaaaaatca agctgttgct gaaattgata atttacaagc attaaatcct 19620 ggacaggttc ttgctgaaaa aacattagtt aaccaagcat caaccaaacc agaagttcaa 19680 gaagccttac aaaaagcaaa agaacttaat gaagctatga aagcactgaa aactgaaata 19740 aataaaaaag aacaaatcaa ggctgatagt agatatgtaa atgctgacag tggtcttcaa 19800 gcaaattaca attctgcgtt aaattatggt tctcaaatta ttgcaactac ccaaccacca 19860 gagcttaata aagatgtaat aaatagagca actcaaacga ttaaaactgc tgaaaataat 19920 ttaaatgggc aatctaaatt agcagaggct aagtcagacg gaaatcaaag catcgaacat 19980 ttgcaaggat taacacaatc acaaaaagat aaacaacatg atttaattaa tcaagctcaa 20040 actaaacaac aggtagatga tatcgtaaat aactctaaac aattagataa ctctatgaat 20100 caactacaac aaattgttaa caatgacaat acagtaaaac aaaatagtga tttcattaat 20160 gaagattcca gccaacagga tgcttataat catgcaattc aagcagcaaa agatttgata 20220 actgctcatc caactatcat ggataaaaat caaatagatc aagctattga aaatatcaaa 20280 caagcactta atgatttaca cggtagtaat aaactatcag aagataaaaa agaagcttca 20340 gaacaactac aaaaccttaa tagcttgacg aacgggcaaa aagatacgat tttaaatcat 20400 attttcagtg caccaacaag aagccaagta ggagaaaaaa ttgcaagtgc taaacaatta 20460 aataatacaa tgaaagcact tagagattct attgctgata ataatgaaat tttacaaagt 20520 agtaagtact tcaatgaaga ttctgaacaa caaaatgctt ataatcaagc cgtaaataaa 20580 gctaaaaata taattaatga tcaaccaaca ccagtaatgg caaatgatga gattcaaagt 20640 gtcctaaatg aagttaaaca aactaaagat aatttacatg gtgatcaaaa acttgctaac 20700 gacaagacag atgctcaagc aacattaaat gcgttaaatt acttaaatca agcgcaaaga 20760 ggtaatcttg aaactaaagt tcaaaactct aattctagac cagaagtaca aaaagtagtt 20820 caattagcaa atcaacttaa tgatgcgatg aaaaaattag atgatgcttt aactggtaat 20880 gacgcaataa aacaaacgag taattatatt aatgaagata cttctcaaca agttaacttt 20940 gatgagtata cagatagagg taaaaacata gttgctgaac aaacaaatcc aaatatgtct 21000 ccaactaata ttaacactat tgctgataaa attactgaag ctaaaaacga tttacatggc 21060 gtacaaaaac taaaacaagc tcaacaacag tccatcaata ctattaatca aatgactggt 21120 ctaaaccaag ctcaaaaaga acaattaaat caagaaattc aacaaactca aacccgttct 21180 gaagtacatc aagtaattaa taaagcacaa gctttaaatg attcaatgaa tactttacgt 21240 caaagtatta ctgatgaaca tgaagttaaa caaacaagta actacatcaa tgaaactgtt 21300 ggtaatcaaa ctgcatataa caatgccgtt gatcgtgtaa aacaaataat caatcaaaca 21360 tctaatccaa ctatgaatcc tttagaggtg gaacgtgcaa catcaaatgt aaaaatttct 21420 aaagatgcac ttcatggtga acgtgaattg aatgacaata aaaattcaaa aacttttgca 21480 gtcaatcact tagataacct caatcaagct caaaaagaag cattaactca tgaaattgaa 21540 caagcaacta tagtttcaca agtaaataat atctataaca aagcgaaagc tttaaataat 21600 gatatgaaaa aacttaaaga tatcgttgct caacaagata atgtgagaca atcaaacaat 21660 tatataaacg aggatagtac acctcaaaat atgtacaacg atacaattaa tcatgcacaa 21720 tcaatcattg atcaagtagc aaaccctacg atgtctcatg acgaaataga gaatgcaatc 21780 aataacataa agcatgccat caatgcactc gatggagaac ataaattaca acaagcaaaa 21840 gaaaatgcaa acttattgat taatagttta aacgatttaa atgcaccaca aagagatgcc 21900 ataaatagat tggttaatga agctcaaaca agagaaaaag tagctgaaca acttcaaagt 21960 gctcaagctt taaatgacgc tatgaagcat ttaagaaaca gcattcaaaa tcaatcatcc 22020 gtaagacaag agagcaaata tattaatgca agtgatgcta aaaaagagca atataatcac 22080 gcagttagag aagtcgaaaa tattatcaat gaacaacatc caacattgga taaagaaata 22140 attaagcaac taacggatgg tgtaaatcaa gcgaataatg acttaaatgg cgttgaatta 22200 ttagatgctg ataagcaaaa cgcacatcaa tcgataccta cattgatgca cttaaatcaa 22260 gcacaacaaa acgcattaaa tgaaaaaatt aataacgcag ttaccagaac tgaagttgcg 22320 gctattattg gccaagcaaa actactcgat catgctatgg agaatttaga agaaagtatc 22380 aaagataaag agcaagtcaa acagtcaagt aactatatta atgaagattc tgatgttcaa 22440 gaaacatacg ataacgccgt tgatcatgtg acagaaatac ttaatcaaac agtaaatcca 22500 actttatcta ttgaagatat agagcatgct atcaacgaag ttaatcaagc gaaaaaacaa 22560 ctcagaggta aacaaaaact ttatcaaact atcgatttag ctgataaaga attaagtaaa 22620 ttggatgatt taacatcaca acaaagcagt tcaatatcta atcaaatata tactgctaaa 22680 acgagaacag aagttgccca agcaattgaa aaagcaaaat cattaaatca tgcaatgaaa 22740 gcacttaaca aagtatataa aaatgcagat aaagtgttag atagtagtcg attcattaac 22800 gaagatcaac ctgaaaaaaa ggcgtatcaa caagctataa atcatgttga ttcaatcatt 22860 catagacaaa caaatcctga aatggatcca acagtaatca atagcataac tcatgaactc 22920 gaaacagctc aaaataactt acatggtgat cagaaacttg ctcatgcaca acaagatgcc 22980 gctaatgtaa ttaatggtct aattcatctt aatgttgctc aacgtgaggt aatgataaat 23040 acgaatacaa atgctacaac acgcgaaaaa gttgcaaaga acttagataa tgctcaagct 23100 cttgataaag ctatggaaac actacaacaa gtagttgctc ataaaaataa tatattgaac 23160 gatagtaaat atttaaatga agattcaaaa tatcaacaac aatacgatcg agttattgct 23220 gatgccgaac aactacttaa tcagacaaca aatccaacat tagaacctta taaagtcgat 23280 attgttaagg ataatgtcct agctaacgaa aaaatactat ttggcgcaga aaaactatca 23340 tatgacaaat caaatgcaaa tgatgaaatt aaacatatga attatcttaa taatgcacaa 23400 aagcaatcta taaaagatat gatttctcac gcagcattaa gaactgaagt taaacaactt 23460 ctgcaacaag ctaaaatcct tgatgaagcc atgaaatcac ttgaagataa aactcaagta 23520 gtgattacag atactacttt gcctaattac actgaagctt cagaggataa aaaggaaaaa 23580 gtagaccaaa ctgtatcaca tgctcaagcg attattgata aaataaatgg ctcaaatgta 23640 agtttagatc aagtacgaca agcactagaa caattaactc aagcatcaga aaacctcgat 23700 ggtgatcagc gagttgaaga agctaaagtt catgctaatc aaacaattga tcaattaaca 23760 catcttaatt cattacaaca acaaactgcg aaagaaagtg ttaaaaacgc aacaaaacta 23820 gaagaaatcg ctactgttag taacaatgct caggcattaa acaaagtaat gggtaaatta 23880 gaacaattca ttaatcatgc tgattctgtt gaaaatagtg ataattatag acaagccgac 23940 gacgacaaaa tcatcgctta tgatgaagca cttgaacatg gacaagatat acaaaaaact 24000 aacgcaaccc aaaatgaaac aaaacaagcg ttacaacaat taatatatgc agaaacatcg 24060 ttaaatggtt tcgaaagatt aaatcatgct agaccacgag ctttagaata tatcaaatca 24120 ctagaaaaaa taaacaatgc tcaaaagtct gctttagagg ataaagtaac gcaatcgcat 24180 gatttattag aattagaaca tattgtcaac gagggcacaa acctcaatga cattatgggt 24240 gaattagcta acgcaatcgt taataactat gctccaacca aagcaagtat aaattatatt 24300 aacgccgata acctacgcaa agataacttt actcaagcta tcaacaatgc acgtgatgca 24360 ctcaacaaaa ctcaaggtca gaacttagat ttcaatgcaa ttgatacatt taaagatgat 24420 atattcaaaa ctaaagatgc acttaacggt attgaacgtt taacagctgc aaaatcaaaa 24480 gcagaaaaac taattgatag tttaaaattt attaataaag ctcaattcac acatgcaaat 24540 gatgaaatta tgaatactaa ttctattgca caattgtcta gaatcgtgaa tcaagcattt 24600 gatttaaatg atgcaatgaa atctttaaga gatgaactta ataatcaagc ttttcctgtc 24660 caagcaagct caaattatat aaattcagat gaagatttaa aacaacaatt tgaccatgct 24720 ttaagtaatg ctcgaaaagt tcttgcaaaa gaaaatggta aaaatttaga tgaaaaacaa 24780 attcagggac tcaaacaagt gattgaggat actaaagatg ctttaaatgg tatccaacgt 24840 ttatcaaaag ctaaagctaa agcaattcaa tacgtacaat ctttatctta tatcaatgat 24900 gcacagcgtc atattgctga aaataatatt cacaactctg atgatttatc atctttagca 24960 aatacattat ctaaagctag tgatttagat aatgcaatga aagacttacg agatactata 25020 gaaagtaatt caacttctgt tccaaatagt gtgaattata ttaatgctga taagaattta 25080 caaattgaat ttgatgaggc gctacaacaa gcaagtgcaa caagttctaa aacttcagaa 25140 aatccagcaa cgattgaaga agtattaggt cttagtcaag ccatttacga tacaaaaaat 25200 gcattaaatg gtgaacaacg acttgcaact gagaagagca aagatctaaa attaataaaa 25260 ggattaaaag atttaaataa agcacaactt gaagatgtca caaacaaggt aaattcagca 25320 aatactttaa cagagttatc tcagctcact caatcaacgt tagaattaaa cgataaaatg 25380 aaattattga gagataagct taaaacttta gtaaatcctg ttaaagcaag

tttaaattat 25440 agaaacgctg attataattt aaaacgtcaa tttaacaaag ctttaaaaga agctaaaggc 25500 gtattaaata aaaatagcgg tacaaatgtc aatatcaatg acattcaaca tcttttaaca 25560 caaatagata atgctaaaga ccaattaaat ggtgaacgac gtctaaaaga acatcaacaa 25620 aaatctgaag tatttattat taaagaatta gatatactta ataatgctca aaaagctgca 25680 ataattaatc agattagagc gtctaaagac attaaaataa ttaatcaaat cgttgataat 25740 gcaatagaat taaatgatgc tatgcaaggt ttaaaagaac atgtagctca attaacagca 25800 actacaaaag acaacattga atatttaaat gctgatgaag accataaatt acaatatgat 25860 tacgctatca acttagcgaa taatgttctt gacaaagaaa acggtacaaa taaagacgct 25920 aatatcataa ttggaatgat tcaaaacatg gatgatgcta gagcacttct aaatggaatt 25980 gaaagactta aagatgctca aacaaaagca cataatgaca ttaaagatac gctcaaacgt 26040 caacttgatg aaattgaaca cgctaatgca acatcaaatt ctaaagctca agctaaacaa 26100 atggtaaatg aggaagctag aaaagcgctt tctaatatta atgacgcaac atcaaatgat 26160 ttagttaatc aagcaaaaga tgaagggcaa tctgcaattg aacacataca tgcagatgaa 26220 ttacctaaag caaaactaga tgctaatcaa atgattgacc aaaaagttga agatataaat 26280 cacttaatta gtcaaaatcc aaacttatca aatgaagaaa aaaataaact aatatctcaa 26340 attaataagt tagtaaatgg aattaagaat gaaattcaac aagctataaa caaacaacaa 26400 atagaaaatg ctacaacaaa actagatgaa gtcattgaaa ctactaaaaa attaattatc 26460 gccaaagcag aagctaaaca aatgataaaa gagttatcac aaaagaaacg agatgcaata 26520 aataacaaca ctgatttaac accttctcaa aaggcacatg ctttagcaga tattgataaa 26580 acagaaaaag atgcacttca acatatcgaa aattctaatt caattgatga tatcaataac 26640 aataaagagc atgcatttaa tactttagct catatcatta tttgggatac tgatcagcaa 26700 ccattagttt ttgaactacc tgaattgagc cttcaaaatg ctctagtaac aagtgaggtg 26760 gttgttcaca gagatgaaac tatttcatta gaatctataa ttggagctat gactttaact 26820 gatgaactta aagtcaatat tgtttcatta ccgaacactg ataaagtagc tgatcaccta 26880 accgctaaag ttaaggttat tttagctgat ggctcatatg tcactgtaaa tgttccagtc 26940 aaagttgtag aaaaagaatt acaaatagct aaaaaggatg ctataaaaac aattgatgtt 27000 ctggtaaaac aaaaaatcaa agatatagat tctaataacg aattaacgtc tactcaacgt 27060 gaagatgcaa aagctgaaat tgaaagattg aaaaagcaag ccatcgataa agtgaatcat 27120 tcaaaatcga ttaaagatat tgaaacagta aaacgaactg attttgaaga aatagatcag 27180 tttgatccta aacgctttac gctaaataaa gctaaaaagg atatcattac tgatgttaat 27240 actcaaatcc aaaatggttt caaagaaatt gaaacaataa aaggtttaac ttctaatgaa 27300 aaaactcagt ttgataaaca attaactgca ctacaaaaag aatttttaga aaaagtcgag 27360 catgctcata atttagtaga attaaatcaa ttacaacaag agtttaataa tagatataaa 27420 catattttaa accaagcaca tttactaggt gaaaaacata tagcagaaca taaattagga 27480 tatgttgtag taaacaaaac tcagcaaata ctaaataatc aatctgcttc ttactttata 27540 aaacaatggg cacttgatag aattaaacaa attcaactag aaacgatgaa ttcaattcgt 27600 ggtgcgcata ccgtacaaga tgtacacaaa gcattattac aaggtataga gcaaatcttg 27660 aaagtaaatg taagtattat aaatcaatct ttcaacgatt ccttgcataa ctttaattat 27720 cttcattcaa aatttgatgc tagattaaga gaaaaggatg ttgcaaacca tatcgtacaa 27780 actgaaacat tcaaagaagt tctaaaagga acgggtgttg aaccaggtaa aatcaacaaa 27840 gaaacacagc aaccaaaact tcataagaat gataatgata gcctattcaa acatttagtt 27900 gataatttcg gcaaaactgt aggtgttatt acattaactg gtttactttc tagtttctgg 27960 ttagttttgg ctaaaagacg taaaaaagaa gaagaagaaa aacaatcgat aaaaaatcat 28020 cacaaagata ttcgtctttc agatactgat aaaatagatc caattgtaat aactaagcgt 28080 aaaatagata aagaagaaca aattcaaaac gatgacaaac attcaattcc agttgctaaa 28140 cataagaaat ctaaagaaaa gcaattgagt gaagaggata ttcattcaat ccccgtcgtt 28200 aagcgtaaac aaaacagtga taacaaagat acaaaacaga agaaagttac ttctaaaaag 28260 aagaaaacgc ctcagtcaac taaaaaagtt gtaaaaacca aaaagcgttc taaaaag 28317 49 3348 DNA S. aureus 49 atgagagata agaaaggacc ggtaaataaa agagtagatt ttctatcaaa taaattgaat 60 aaatattcaa taagaaaatt tacagttgga acagcatcta ttttaattgg ctcactaatg 120 tatttgggaa ctcaacaaga agcagaagca gctgaaaaca atattgagaa tccaactaca 180 ttaaaagata atgtccaatc aaaagaagtg aagattgaag aagtaacaaa caaagacact 240 gcaccacaag gtgtagaagc taaatctgaa gtaacttcaa acaaagacac aatcgaacat 300 gaagcatcag taaaagctga agatatatca aaaaaggagg atacaccaaa agaagtagct 360 aatgttgctg aagttcagcc gaaatcgtca gtcactcata acgcagaggc acctaaggtt 420 agaaaagctc gttctgttga tgaaggctct tttgatatta caagagattc taaaaatgta 480 gttgaatcta ccccaattac aattcaaggt aaagaacatt ttgaaggtta cggaagtgtt 540 gatatacaaa aaaacccaac agatttaggg gtatcagagg taaccaggtt taatgttggt 600 aatgaaagta atggtttgat aggagcttta caattaaaaa ataaaataga ttttagtaag 660 gatttcaatt ttaaagttag agtggcaaat aaccatcaat caaataccac aggtgctgat 720 ggttgggggt tcttatttag taaaggaaat gcagaagaat atttaactaa tggtggaatc 780 cttggggata aaggtctggt aaattcaggc ggatttaaaa ttgatactgg atacatttat 840 acaagttcca tggacaaaac tgaaaagcaa gctggacaag gttatagagg atacggagct 900 tttgtgaaaa atgacagttc tggtaattca caaatggttg gagaaaatat tgataaatca 960 aaaactaatt ttttaaacta tgcggacaat tcaactaata catcagatgg aaagtttcat 1020 gggcaacgtt taaatgatgt catcttaact tatgttgctt caactggtaa aatgagagca 1080 gaatatgctg gtaaaacttg ggagacttca ataacagatt taggtttatc taaaaatcag 1140 gcatataatt tcttaattac atctagtcaa agatggggcc ttaatcaagg gataaatgca 1200 aatggctgga tgagaactga cttgaaaggt tcagagttta cttttacacc agaagcgcca 1260 aaaacaataa cagaattaga aaaaaaagtt gaagagattc cattcaagaa agaacgtaaa 1320 tttaatccgg atttagcacc agggacagaa aaagtaacaa gagaaggaca aaaaggtgag 1380 aagacaataa caacaccaac actaaaaaat ccattaactg gagaaattat tagtaaaggt 1440 gaatcgaaag aagagatcac aaaagatccg attaatgaat taacagaata cggaccagaa 1500 acgatagcac caggtcatcg agacgaattt gatccgaagt taccaacagg agagaaagaa 1560 gaagttccag gtaaaccagg aattaagaat ccagaaacag gagacgtagt tagaccaccg 1620 gtcgatagtg taacaaaata tggacctgta aaaggagact cgattgtaga aaaagaagaa 1680 attccattcg agaaagaacg taaatttaat cctgatttag caccaggaac agaaaaagta 1740 acaagagaag gacaaaaagg tgagaagaca ataacgacac caacactaaa aaatccatta 1800 actggagaaa ttattagtaa aggtgaatcg aaagaagaga tcacaaaaga tccgattaat 1860 gaattaacag aatacggacc tgaaacaata gcgccaggtc atcgagacga atttgatccg 1920 aagttaccaa caggagagaa agaagaagtt ccaggtaaac caggaattaa gaatccagaa 1980 acaggagacg tagttagacc gccggtcgat agcgtaacaa aatatggacc tgtaaaagga 2040 gactcgattg tagaaaaaga agaaattcca ttcaagaaag aacgtaaatt taatcctgat 2100 ttagcaccag ggacagaaaa agtaacaaga gaaggacaaa aaggtgagaa gacaataacg 2160 acgccaacac taaaaaatcc attaactgga gaaattatta gtaaaggtga atcgaaagaa 2220 gaaatcacaa aagatccgat taatgaatta acagaatacg gaccagaaac gataacacca 2280 ggtcatcgag acgaatttga tccgaagtta ccaacaggag agaaagagga agttccaggt 2340 aaaccaggaa ttaagaatcc agaaacagga gatgtagtta gaccaccggt cgatagcgta 2400 acaaaatatg gacctgtaaa aggagactcg attgtagaaa aagaagaaat tccattcgag 2460 aaagaacgta aatttaatcc tgatttagca ccagggacag aaaaagtaac aagagaagga 2520 caaaaaggtg agaagacaat aacgacgcca acactaaaaa atccattaac tggagaaatt 2580 attagtaaag gtgaatcgaa agaagaaatc acaaaagatc cagttaatga attaacagaa 2640 ttcggtggcg agaaaatacc gcaaggtcat aaagatatct ttgatccaaa cttaccaaca 2700 gatcaaacgg aaaaagtacc aggtaaacca ggaatcaaga atccagacac aggaaaagtg 2760 atcgaagagc cagtggatga tgtgattaaa cacggaccaa aaacgggtac accagaaaca 2820 aaaacagtag agataccgtt tgaaacaaaa cgtgagttta atccaaaatt acaacctggt 2880 gaagagcgag tgaaacaaga aggacaacca ggaagtaaga caatcacaac accaatcaca 2940 gtgaacccat taacaggtga aaaagttggc gagggtcaac caacagaaga gatcacaaaa 3000 caaccagtag ataagattgt agagttcggt ggagagaaac caaaagatcc aaaaggacct 3060 gaaaacccag agaagccgag cagaccaact catccaagtg gcccagtaaa tcctaacaat 3120 ccaggattat cgaaagacag agcaaaacca aatggcccag ttcattcaat ggataaaaat 3180 gataaagtta aaaaatctaa aattgctaaa gaatcagtag ctaatcaaga gaaaaaacga 3240 gcagaattac caaaaacagg tttagaaagc acgcaaaaag gtttgatctt tagtagtata 3300 attggaattg ctggattaat gttattggct cgtagaagaa agaattaa 3348 50 4410 DNA S. epidermidis 50 atgggcaaac gtagacaagg tcctattaat aaaaaagtgg attttttacc taacaaatta 60 aacaagtatt ctataagaaa attcactgtt ggtacggcct caatattact tggttcgaca 120 cttatttttg gaagtagtag ccatgaagcg aaagctgcag aagaaaaaca agttgatcca 180 attacacaag ctaatcaaaa tgatagtagt gaaagatcac ttgaaaacac aaatcaacct 240 actgtaaaca atgaagcacc acagatgtct tctacattgc aagcagaaga aggaagcaat 300 gcagaagcac cgaatgttcc aactatcaaa gctaattcag ataatgatac acaaacacaa 360 ttttcagaag cccctacaag aaatgaccta gctagaaaag aagatatccc tgctgtttct 420 aaaaacgagg aattacaatc atcacaacca aacactgaca gtaaaataga acctacaact 480 tcagaacctg tgaatttaaa ttatagttct ccgtttatgt ccttattaag catgcctgct 540 gatagttcat ccaataacac taaaaataca atagatatac cgccaactac ggttaaaggt 600 agagataatt acgattttta cggtagagta gatatccaaa gtaatcctac agatttaaat 660 gcgacaaatt taacgagata taattatgga cagccacctg gtacaacaac agctggtgca 720 gttcaattta aaaatcaagt tagttttgat aaagatttcg actttaacat tagagtagca 780 aacaatcgtc aaagtaatac aactggtgca gatggttggg gctttatgtt cagcaagaaa 840 gatggggatg atttcctaaa aaacggtggt atcttacgtg aaaaaggtac acctagtgca 900 gctggtttca gaattgatac aggatattat aataacgatc cattagataa aatacagaaa 960 caagctggtc aaggctatag agggtatggg acatttgtta aaaatgactc ccaaggtaat 1020 acttctaaag taggatcagg tactccatca acagattttc ttaactacgc agataatact 1080 actaatgatt tagatggtaa attccatggt caaaaattaa ataatgttaa tttgaaatat 1140 aatgcttcaa atcaaacttt tacagctact tatgctggta aaacttggac ggctacgtta 1200 tctgaattag gattgagtcc aactgatagt tacaattttt tagttacatc aagtcaatat 1260 ggaaatggta atagtggtac atacgcagat ggcgttatga gagctgattt agatggtgca 1320 acattgacat atactcctaa agcagtcgat ggagacccaa ttacatcaac taaggaaata 1380 ccatttaata aaaaacgcga atttgatcca aacttagcgc caggtacaga aaaagtcgtt 1440 caaaaaggtg aaccaggaat tgaaacaaca acaacaccaa cttatgtcaa tcctaatact 1500 ggagaaaaag taggtgaagg cacacctaca acaaagatca ctaaacaacc agtggatgaa 1560 atcgttcatt atggtggcga agaaatcaag ccaggacata aagatgaatt tgatccaaat 1620 gcaccgaaag gtagtcaaac aacgcaacca ggtaagccag gagttaaaaa tcctgataca 1680 ggcgaagtag tcacaccacc agtggatgat gtgacaaaat atggtccagt tgatggagat 1740 ccgattacgt caacggaaga aattccattc gacaagaaac gtgaattcaa tcctgattta 1800 aaaccaggtg aagagcgtgt taaacaaaaa ggtgaaccag gaacaaaaac aattacaaca 1860 ccaacaacta agaacccatt aacaggggaa aaagttggcg aaggtgaacc aacagaaaaa 1920 ataacaaaac aaccagtaga tgaaatcaca gaatatggtg gcgaagaaat caagccaggc 1980 cataaggatg aatttgatcc gaacgcaccg aaaggtagcc aagaggacgt tccaggtaaa 2040 ccaggagtta aaaatcctga tacaggcgaa gtagtcacac caccagtgga tgatgtgaca 2100 aaatatggtc cagttgatgg agatccgatt acgtcaacgg aagaaattcc gtttgataaa 2160 aaacgcgaat ttgatccaaa cttagcgcca ggtacagaga aagtcgttca aaaaggtgaa 2220 ccaggaacaa aaacaattac aacaccaaca actaagaacc cattaacagg agaaaaagtt 2280 ggcgaaggtg aaccaacaga aaaaataaca aaacaaccag tggatgaaat cgttcattat 2340 ggtggcgaag aaatcaagcc aggccataag gatgaatttg atccgaacgc accgaaaggt 2400 agccaagagg acgttccagg taagccagga gttaaaaatc ctgatacagg cgaagtagtc 2460 acaccaccag tggatgatgt gacaaaatat ggtccagttg atggagatcc gattacgtca 2520 acggaagaaa ttccattcga caagaaacgt gaattcaatc ctgatttaaa accaggtgaa 2580 gagcgtgtta aacaaaaagg tgaaccagga acaaaaacaa ttacaacacc aacaactaag 2640 aacccattaa caggggaaaa agttggcgaa ggtgaaccaa cagaaaaagt aacaaaacaa 2700 ccagtggatg aaatcgttca ttatggtggc gaagaaatca agccaggcca taaggatgaa 2760 tttgatccaa atgcaccgaa aggtagccaa gaagacgttc caggtaaacc aggagttaaa 2820 aaccctgata caggcgaagt agttactcca ccagtggatg atgtgacaaa atatggtcca 2880 gttgatggag atccgattac gtcaacggaa gaaattccgt ttgataaaaa acgcgaattt 2940 gatccaaact tagcgccagg tacagagaaa gtcgttcaaa aaggtgaacc aggaacaaaa 3000 acaattacaa caccaacaac taagaaccca ttaacaggag aaaaagttgg cgaaggtgaa 3060 ccaacagaaa aaataacaaa acaaccagtg gatgagatcg ttcattatgg tggcgaagaa 3120 atcaagccag gccataagga tgaatttgat ccgaacgcac cgaaaggtag tcaaacaacg 3180 caaccaggta agccaggagt taaaaatcct gatacaggcg aagtagtcac accaccagtg 3240 gatgatgtga caaaatatgg tccagttgat ggagatccga ttacgtcaac ggaagaaatt 3300 ccgtttgata aaaaacgcga atttgatcca aacttagcgc caggtacaga gaaagtcgtt 3360 caaaaaggtg aaccaggaac aaaaacaatt acaacgccaa caactaagaa cccattaaca 3420 ggagaaaaag ttggcgaagg tgaaccaaca gaaaaaataa caaaacaacc agtggatgag 3480 attgttcatt atggtggtga acaaatacca caaggtcata aagatgaatt tgatccaaat 3540 gcacctgtag atagtaaaac tgaagttcca ggtaaaccag gagttaaaaa tcctgataca 3600 ggtgaagttg ttaccccacc agtggatgat gtgacaaaat atggtccgaa agttggtaat 3660 ccaatcacat caacggaaga gattccattt gataagaaac gtgtatttaa tcctgattta 3720 aaaccaggtg aagagcgcgt taaacaaaaa ggtgaaccag gaacaaaaac aattacaaca 3780 ccaatattag ttaatcctat tacaggagaa aaagttggcg aaggtaaatc aacagaaaaa 3840 gtcactaaac aacctgttga cgaaattgtt gagtatggtc caacaaaagc agaaccaggt 3900 aaaccagcgg aaccaggtaa accagcggaa ccaggtaaac cagcggaacc aggtaaacca 3960 gcggaaccag gtacgccagc agaaccaggt aaaccagcgg aaccaggtaa accagcggaa 4020 ccaggtaaac cagcggaacc aggtaaacca gcggaaccag gtaaaccagc ggaaccaggt 4080 acgccagcag aaccaggtaa accagcggaa ccaggtaaac cagcggaacc aggtaaacca 4140 gcggaaccag gtacgccagc agaaccaggt aaaccagcgg aaccaggtac gccagcagaa 4200 ccaggtaaac cagcggaacc aggtacgcca acacaatcag gtgcaccaga acaaccaaat 4260 agatcaatgc attcaacaga taataaaaat caattacctg atacaggtga aaatcgtcaa 4320 gctaatgagg gaactttagt cggatctcta ttagcaattg tcggatcatt gttcatattt 4380 ggtcgtcgta aaaaaggtaa tgaaaaataa 4410 51 504 DNA S. aureus 51 atgaagaaac tatatacatc ttatggcact tatggatttt tacatcaaat aaaaatcaat 60 aacccgaccc atcaactatt ccaattttca gcatcagata cttcagttat ttttgaagaa 120 actgatggtg agactgtttt aaaatcacct tcaatatatg aagttattaa agaaattggt 180 gaattcagtg aacatcattt ctattgtgca atcttcattc cttcaacaga agatcatgca 240 tatcaacttg aaaagaaact gattagtgta gacgataatt tcagaaactt tggtggcttt 300 aaaagctatc gtttgttaag acctgctaaa ggtacaacat ataaaattta tttcggattt 360 gctgatcgac atgcatacga agactttaag caatctgatg cctttaatga ccatttttca 420 aaagacgcat taagtcatta ctttggttca agcggacaac attcaagtta ttttgaaaga 480 tatctatacc caataaaaga atag 504 52 504 DNA S. epidermidis 52 atgtatttat atacatctta tgggacttac caatttttaa atcaaattaa acttaatcat 60 caagaacgta gtttatttca attttccact aatgattcct caataatctt agaagagtct 120 gagggaaaat caatcttaaa acatcctagt gcatatcaag tgattgatag cacaggtgaa 180 tttaacgaac atcattttta tagtgctatt tttgtcccta catctgaaga tcatcgtcaa 240 cagctagaga aaaaattatt actcgtagac gtacctttaa gaaattttgg tggttttaaa 300 agctatcgtt tattaaaacc cactgagggg tctacctaca aaatttactt tggttttgca 360 aatcgaacag catatgaaga tttcaaagct tctgatatat ttaatgaaaa cttttcaaaa 420 gatgcattga gccaatactt tggtgctagt ggtcaacatt ctagctactt tgaaagatat 480 ttatatccaa tagaagatca ttaa 504 53 3426 DNA S. aureus 53 atgattaaca gggataataa aaaggcaata acaaaaaagg gtatgatttc aaatcgctta 60 aacaaatttt cgattagaaa gtatactgta ggaactgcat cgattttagt aggtacgaca 120 ttgatttttg gtctagggaa ccaagaagct aaagctgctg aaaacactag tacagaaaat 180 gcgaaacaag atgatgcaac gactagtgat aataaagaag tagtgtcgga aactgaaaat 240 aattcgacaa cagaaaatga ttcaacaaat ccaattaaga aagaaacaaa tactgattca 300 caaccagaag ctaaagaaga atcaactaca tcaagtactc aacaacagca aaataacgtt 360 acagctacaa ctgaaactaa gcctcaaaac attgaaaaag aaaatgttaa accttcaact 420 gataaaactg cgacagaaga tacatctgtt attttagaag agaagaaagc accaaattat 480 acaaataacg atgtaactac aaaaccatct acaagtgaaa ttcaaacaaa accaactaca 540 cctcaagaat ctacaaatat tgaaaattca caaccgcaac caacgccttc aaaagtagac 600 aatcaagtta cagatgcaac taatccaaaa gaaccagtaa atgtgtcaaa agaagaactt 660 aaaaataatc ctgagaaatt aaaagaatta gttagaaatg ataacaatac agatcgttca 720 actaaaccag ttgctacagc tccaacaagt gttgcaccaa aacgattaaa tgcgaaaatg 780 cgttttgcag ttgcacaacc agcagcagtt gcttcaaata atgtaaatga cttaattaca 840 gttacgaaac agacgatcaa agttggcgat ggtaaagata atgtggcagc agcgcatgac 900 ggtaaagata ttgaatatga tacagagttt acaattgaca ataaagtcaa aaaaggcgat 960 acaatgacga ttaattatga taagaatgta attccttcgg atttaacaga taaaaatgat 1020 cctatcgata ttactgatcc atcaggagag gtcattgcca aaggaacatt tgataaagcg 1080 actaagcaaa tcacatatac atttacagat tatgtagata aatatgaaga tataaaagca 1140 cgtttaactt tatactcata tattgataag caagcagtac ctaatgaaac tagtttgaat 1200 ttaacgtttg caacagcagg taaagaaact agccaaaacg tttctgttga ttatcaagac 1260 ccaatggttc atggtgattc aaacattcaa tctatcttta caaagttaga tgaaaacaaa 1320 caaactattg aacaacaaat ttatgttaat cctttgaaaa aaacagcaac taacactaaa 1380 gttgatatag ctggtagtca agtagatgat tatggaaata ttaaactagg aaatggtagt 1440 accattattg accaaaatac agaaataaaa gtttataaag ttaaccctaa tcaacaattg 1500 cctcaaagta atagaatcta tgattttagt caatacgaag atgtaacaag tcaatttgat 1560 aataaaaaat catttagtaa taatgtagca acattggatt ttggtgatat taattcagcc 1620 tatattatca aagttgttag taaatataca cctacatcag atggcgaact agatattgct 1680 caaggtacta gtatgagaac aactgataaa tatggttatt ataattatgc aggatattca 1740 aacttcatcg taacttctaa tgacactggc ggtggcgacg gtactgttaa acctgaagaa 1800 aagttataca aaattggtga ctatgtatgg gaagacgttg ataaagacgg tgtccaaggt 1860 acagattcga aagaaaagcc aatggcaaac gttttagtta cattaactta cccggacggt 1920 actacaaaat cagtaagaac agatgctaac ggtcattatg aattcggtgg tttgaaagac 1980 ggagaaactt atacagttaa attcgaaacg ccagctggat atcttccaac aaaagtaaat 2040 ggaacaactg atggtgaaaa agactcaaat ggtagttcta taactgttaa aattaatggt 2100 aaagatgata tgtctttaga cactggtttt tataaagaac ctaaatataa tcttggtgac 2160 tatgtatggg aagatacaaa taaagatggt atccaagatg ctaatgaacc tggtatcaaa 2220 gatgttaagg ttacattaaa agatagtact ggaaaagtta ttggtacaac tactactgat 2280 gcctcgggta aatataaatt tacagattta gataatggta actatacagt agaatttgaa 2340 acaccagcag gttacacgcc aacggttaaa aatactacag ctgaagataa agattctaat 2400 ggtttaacaa caacaggtgt cattaaagat gcagataata tgacattaga cagtggtttc 2460 tataaaacac caaaatacag tttaggtgat tatgtttggt acgacagtaa taaagacggt 2520 aaacaagatt caactgaaaa aggtatcaaa gatgttaaag ttactttatt aaatgaaaaa 2580 ggcgaagtaa ttggaacaac taaaacagat gaaaatggta aatatcgttt cgataattta 2640 gatagcggta aatacaaagt tatttttgaa aagcctgctg gcttaacaca aacagttaca 2700 aatacaactg aagatgataa agatgccgat ggtggcgaag ttgacgtaac aattacggat 2760 catgatgatt tcatacttga taacggatac ttcgaagaag atacatcaga cagtgattca 2820 gactcagaca gtgattcaga ctcagacagc gactcagatt cagacagtga ttcagactca 2880 gatagcgatt cagattcaga cagcgactca gactcagata gcgactcaga ctcagacagc 2940 gactcagact cagatagcga ctcagattcg gacagcgatt cagactcaga tagcgactca 3000 gattcagaca gcgattcaga ctcagatagc gactcagatt cagacagtga ctcagactca 3060 gatagcgact cagactcaga cagtgactca gactcagaca gcgattcaga ttcagatagc 3120 gactcagatt cggacagtga

ttcagactca gatagcgact cagattcaga cagcgactca 3180 gactcagata gcgactcaga ctcagacagt gattcagact cagatagcga ttcggactcg 3240 gatgcaggaa aacatacacc tgttaaacca atgagtacta ctaaagacca tcacaataaa 3300 gcaaaagcat taccagaaac aggtagtgaa aataacggct caaataacgc aacgttattt 3360 ggtggattat ttgcagcatt aggttcatta ttgttattcg gtcgtcgcaa aaaacaaaac 3420 aaataa 3426 54 3171 DNA S. epidermidis 54 atgattaata aaaaaaataa tttactaact aaaaagaaac ctatagcaaa taaatccaat 60 aaatatgcaa ttagaaaatt cacagtaggt acagcgtcta ttgtaatagg tgcaacatta 120 ttgtttggtt taggtcataa tgaggccaaa gccgaggaga attcagtaca agacgttaaa 180 gattcgaata cggatgatga attatcagac agcaatgatc agtctagtga tgaagaaaag 240 aatgatgtga tcaataataa tcagtcaata aacaccgacg ataataacca aataattaaa 300 aaagaagaaa cgaataacta cgatggcata gaaaaacgct cagaagatag aacagagtca 360 acaacaaatg tagatgaaaa cgaagcaaca tttttacaaa agacccctca agataatact 420 catcttacag aagaagaggt aaaagaatcc tcatcagtcg aatcctcaaa ttcatcaatt 480 gatactgccc aacaaccatc tcacacaaca ataaatagag aagaatctgt tcaaacaagt 540 gataatgtag aagattcaca cgtatcagat tttgctaact ctaaaataaa agagagtaac 600 actgaatctg gtaaagaaga gaatactata gagcaaccta ataaagtaaa agaagattca 660 acaacaagtc agccgtctgg ctatacaaat atagatgaaa aaatttcaaa tcaagatgag 720 ttattaaatt taccaataaa tgaatatgaa aataaggcta gaccattatc tacaacatct 780 gcccaaccat cgattaaacg tgtaaccgta aatcaattag cggcggaaca aggttcgaat 840 gttaatcatt taattaaagt tactgatcaa agtattactg aaggatatga tgatagtgaa 900 ggtgttatta aagcacatga tgctgaaaac ttaatctatg atgtaacttt tgaagtagat 960 gataaggtga aatctggtga tacgatgaca gtggatatag ataagaatac agttccatca 1020 gatttaaccg atagctttac aataccaaaa ataaaagata attctggaga aatcatcgct 1080 acaggtactt atgataacaa aaataaacaa atcacctata cttttacaga ttatgtagat 1140 aagtatgaaa atattaaagc acaccttaaa ttaacgtcat acattgataa atcaaaggtt 1200 ccaaataata ataccaagtt agatgtagaa tataaaacgg ccctttcatc agtaaataaa 1260 acaattacgg ttgaatatca aagacctaac gaaaatcgga ctgctaacct tcaaagtatg 1320 tttacaaaca tagatacgaa aaatcataca gttgagcaaa cgatttatat taaccctctt 1380 cgttattcag ccaaggaaac aaatgtaaat atttcaggga atggtgatga aggttcaaca 1440 attatagacg atagcacaat aattaaagtt tataaggttg gagataatca aaatttacca 1500 gatagtaaca gaatttatga ttacagtgaa tatgaagatg tcacaaatga tgattatgcc 1560 caattaggaa ataataatga tgtgaatatt aattttggta atatagattc accatatatt 1620 attaaagtta ttagtaaata tgaccctaat aaggatgatt acacgactat acagcaaact 1680 gtgacaatgc agacgactat aaatgagtat actggtgagt ttagaacagc atcctatgat 1740 aatacaattg ctttctctac aagttcaggt caaggacaag gtgacttgcc tcctgaaaaa 1800 acttataaaa tcggagatta cgtatgggaa gatgtagata aagatggtat tcaaaataca 1860 aatgataatg aaaaaccgct tagtaatgta ttggtaactt tgacgtatcc tgatggaact 1920 tcaaaatcag tcagaacaga tgaagatggg aaatatcaat ttgatggatt gaaaaacgga 1980 ttgacttata aaattacatt cgaaacacct gaaggatata cgccgacgct taaacattca 2040 ggaacaaatc ctgcactaga ctcagaaggt aattctgtat gggtaactat taatggacaa 2100 gacgatatga cgattgatag tggattttat caaacaccta aatacagctt agggaactat 2160 gtatggtatg acactaataa agatggtatt caaggtgatg atgaaaaagg aatctctgga 2220 gttaaagtga cgttaaaaga tgaaaacgga aatatcatta gtacaactac aaccgatgaa 2280 aatggaaagt atcaatttga taatttaaat agtggtaatt atattgttca ttttgataaa 2340 ccttcaggta tgactcaaac aacaacagat tctggtgatg atgacgaaca ggatgctgat 2400 ggggaagaag ttcatgtaac aattactgat catgatgact ttagtataga taacggatac 2460 tatgatgacg aatcggattc cgatagtgac tcagacagcg actcagattc cgatagtgat 2520 tcagactccg atagcgactc ggattcagac agcgactcag attcagacag cgactcggat 2580 tctgatagcg actcggattc agacagcgac tcagactcag acagtgattc agattcagac 2640 agcgactcag attccgatag tgattcagac tcagacagcg actcagattc tgatagtgat 2700 tcagactcag acagtgattc agattcagac agcgactcag attccgatag tgattcagac 2760 tcagacagcg actcagattc cgatagtgat tcagactcag acagcgactc agattctgat 2820 agtgattcag actcagacag tgattcagat tccgatagtg attcagactc cgatagcgac 2880 tcagactcgg atagtgactc agattctgat agtgattcag actcagacag tgattcggat 2940 tccgatagtg attcagactc agacagcgac tcagattctg atagtgattc agactcagac 3000 aacgactcag atttaggcaa tagctcagat aagagtacaa aagataaatt acctgataca 3060 ggagctaatg aagattatgg ctctaaaggc acgttacttg gaactctgtt tgcaggttta 3120 ggagcgttat tattagggaa acgtcgcaaa aatagaaaaa ataaaaatta a 3171 55 1461 DNA S. aureus 55 atgtctaata attttaaaga tgactttgaa aaaaatcgtc aatcgataga cacaaattca 60 catcaagacc atacggaaga tgttgaaaaa gaccaatcag aattagaaca tcaggataca 120 atagagaata cggagcaaca gtttccgcca agaaatgccc aaagaagaaa aagacgccgt 180 gatttagcaa cgaatcataa taaacaagtt cacaatgaat cacaaacatc tgaagacaat 240 gttcaaaatg aggctggcac aatagatgat cgtcaagtcg aatcatcaca cagtactgaa 300 agtcaagaac ctagccatca agacagtaca cctcaacatg aagaggaata ttataataag 360 aatgcttttg caatggataa atcacatcca gaaccaatcg aagacaatga taaacacgag 420 actattaaag atgcagaaaa taacactgag cattcaacag tttctgataa gagtatagct 480 gaacaatctc agcaacctaa accatatttt gcaacaggtg ctaaccaagc aaatacatca 540 aaagataaac atgatgatgt aactgttaag caagacaaag atgaatctaa agatcatcat 600 agtggtaaaa aaggcgcagc aattggtgct ggaacagcgg gtgttgcagg tgcagctggt 660 gcaatgggtg tttctaaagc taagaaacat tcaaatgacg ctcaaaacaa aagtaattct 720 gacaagtcga ataactcgac tgaggataaa gcgtctcaag ataagtctaa agatcatcat 780 aatggcaaaa aaggtgcagc gatcggtgct ggaacagcag gtttggctgg aggcgcagca 840 agtaaaagtg cttctgccgc ttcaaaacca catgcctcta ataatgcaag ccaaaaccat 900 gatgaacatg acaatcatga cagagataaa gaacgtaaaa aaggtggcat ggccaaagta 960 ttgttaccat taattgcagc tgtactaatt atcggtgcat tagcgatatt tggaggcatg 1020 gcattaaaca atcataataa tggtacaaaa gaaaataaaa tcgcgaatac aaataaaaat 1080 aatgctgatg aaagtaaaga caaagacaca tctaaagacg cttctaaaga taaatcaaaa 1140 tctacagaca gtgataaatc aaaagaggat caagacaaag cgactaaaga tgaatctgat 1200 aatgatcaaa acaacgctaa tcaagcgaac aatcaagcac aaaataatca aaatcaacaa 1260 caagctaatc aaaatcaaca acagcaacaa caacgtcaag gtggtggcca aagacataca 1320 gtgaatggtc aagaaaactt ataccgtatc gcaattcaat actacggttc aggttcaccg 1380 gaaaatgttg aaaaaattag acgtgccaat ggtttaagtg gtaacaatat tagaaacggt 1440 caacaaatcg ttattccata a 1461 56 1419 DNA S. epidermidis 56 gtgattgaat taattaaaat ggaagggatg atagttgtgt ctaataataa ttttaaagat 60 gatttcgaaa agaatcgtca atctattaat ccagacgaac agcaaacaga attaaaagaa 120 gatgataaaa caaatgaaaa taaaaaagaa gctgactctc aaaacagttt atctaataac 180 tcaaatcaac aatttcctcc gagaaatgcc caacgacgaa aaagacgtag agagacagca 240 actaatcaaa gcaaacaaca agacgacaaa catcaaaaaa atagtgacgc taaaactaca 300 gaaggttcat tagatgaccg ttatgacgaa gcacagttac agcaacaaca tgataaatcg 360 caacaacaaa ataaaactga aaaacaatca caagataata gaatgaaaga tggaaaagat 420 gcagctattg taaatggaac atctgagtca ccagaacata aatcaaaatc aacacaaaat 480 agacccggcc ctaaagctca acaacaaaag cgtaaatcag aaagtacgca atcaaaaccg 540 tcaacaaaca aagataaaaa agcagctaca ggtgctggaa tagctggtgc agctggtgtt 600 gctggtgcag cagaaacatc caaacgtcat cataataaaa aagataaaca agattctaaa 660 cactcaaacc atgagaatga cgaaaaatct gttaaaaatg atgaccaaaa gcaatctaaa 720 aaaggcaaaa aagcagcagt cggtgctggc gcagctgcag gagttggtgc ggctggtgtt 780 gcgcatcata ataatcaaaa taaacatcat aatgaggaaa aaaattctaa tcaaaacaat 840 cagtacaatg accaatcaga aggtaagaaa aaaggtggtt tcatgaaaat cttgttacca 900 cttatagcag ccattcttat tctaggtgca atagcaatat tcggtggtat ggctctaaat 960 aatcacaacg atagtaaaag tgatgaccaa aaaatagcga atcaaagtaa gaaagactca 1020 gataaaaaag atggtgcgca atccgaagat aacaaagaca aaaaatctga tagtaacaaa 1080 gacaaaaaat ctgattctga taagaacgca gatgatgact ctgataatag ttcctcaaat 1140 cctaacgcta cttcaactaa taataacgat aatgtagcca ataataactc aaattataca 1200 aaccaaaatc aacaagataa tgcaaaccaa aatagcaata atcaacaggc aactcaaggt 1260 caacaatcac atacagtata cggtcaagaa aacttatatc gtatcgccat acaatattat 1320 ggagaaggaa ctcaagctaa cgtagataaa attaaacgtg cgaatggatt aagcagtaat 1380 aatattcata atggtcaaac attagttatt cctcaataa 1419 57 498 DNA S. aureus 57 atgaaaaata aattgatagc aaaatcttta ttaacaatag cggcaattgg tattactaca 60 actacaattg cgtcaacagc agatgcgagc gaaggatacg gtccaagaga aaagaaacca 120 gtgagtatta atcacaatat cgtagagtac aatgatggta cttttaaata tcaatctaga 180 ccaaaattta actcaacacc taaatatatt aaattcaaac atgactataa tattttagaa 240 tttaacgatg gtacattcga atatggtgca cgtccacaat ttaataaacc agcagcgaaa 300 actgatgcaa ctattaaaaa agaacaaaaa ttgattcaag ctcaaaatct tgtgagagaa 360 tttgaaaaaa cacatactgt cagtgcacac agaaaagcac aaaaggcagt caacttagtt 420 tcgtttgaat acaaagtgaa gaaaatggtc ttacaagagc gaattgataa tgtattaaaa 480 caaggattag tgagataa 498 58 960 DNA S. aureus 58 atgaaaacac gtatagtcag ctcagtaaca acaacactat tgctaggttc catattaatg 60 aatcctgtcg ctaatgccgc agattctgat attaatatta aaaccggtac tacagatatt 120 ggaagcaata ctacagtaaa aacaggtgat ttagtcactt atgataaaga aaatggcatg 180 cacaaaaaag tattttatag ttttatcgat gataaaaatc acaataaaaa actgctagtt 240 attagaacga aaggtaccat tgctggtcaa tatagagttt atagcgaaga aggtgctaac 300 aaaagtggtt tagcctggcc ttcagccttt aaggtacagt tgcaactacc tgataatgaa 360 gtagctcaaa tatctgatta ctatccaaga aattcgattg atacaaaaga gtatatgagt 420 actttaactt atggattcaa cggtaatgtt actggtgatg atacaggaaa aattggcggc 480 cttattggtg caaatgtttc gattggtcat acactgaaat atgttcaacc tgatttcaaa 540 acaattttag agagcccaac tgataaaaaa gtaggctgga aagtgatatt taacaatatg 600 gtgaatcaaa attggggacc atatgataga gattcttgga acccggtata tggcaatcaa 660 cttttcatga aaactagaaa tggttctatg aaagcagcag agaacttcct tgatcctaac 720 aaagcaagtt ctctattatc ttcagggttt tcaccagact tcgctacagt tattactatg 780 gatagaaaag catccaaaca acaaacaaat atagatgtaa tatacgaacg agttcgtgat 840 gactaccaat tgcattggac ttcaacaaat tggaaaggta ccaatactaa agataaatgg 900 acagatcgtt cttcagaaag atataaaatc gattgggaaa aagaagaaat gacaaattaa 960 59 1287 DNA S. aureus 59 atacacatga aaaataaata tatctcgaag ttgctagttg gggcagcaac aattacttta 60 gctacaatga tttcaaatgg ggaagcaaaa gcgagtgaaa acacgcaaca aacttcaact 120 aagcaccaaa caactcaaaa caactacgta acagatcaac aaaaagcttt ttatcaagta 180 ttacatctaa aaggtatcac agaagaacaa cgtaaccaat acatcaaaac attacgcgaa 240 cacccagaac gtgcacaaga agtattctct gaatcactta aagacagcaa gaacccagac 300 cgacgtgttg cacaacaaaa cgctttttac aatgttctta aaaatgataa cttaactgaa 360 caagaaaaaa ataattacat tgcacaaatt aaagaaaacc ctgatagaag ccaacaagtt 420 tgggtagaat cagtacaatc ttctaaagct aaagaacgtc aaaatattga aaatgcggat 480 aaagcaatta aagatttcca agataacaaa gcaccacacg ataaatcagc agcatatgaa 540 gctaactcaa aattacctaa agatttacgc gataaaaata accgctttgt agaaaaagtt 600 tcaattgaaa aagcaatcgt tcgtcatgat gagcgtgtga aatcagcaaa tgatgcaatc 660 tcaaaattaa atgaaaaaga ttcaattgaa aacagacgtt tagcacaacg tgaagttaac 720 aaagcaccta tggatgtaaa agagcattta cagaaacaat tagacgcatt agtagctcaa 780 aaagatgctg aaaagaaagt ggcgccaaaa gttgaggctc ctcaaattca atcaccacaa 840 attgaaaaac ctaaagcaga atcaccaaaa gttgaagtcc ctcaatctaa attattaggt 900 tactaccaat cattaaaaga ttcatttaac tatggttaca agtatttaac agatacttat 960 aaaagctata aagaaaaata tgatacagca aagtactact ataatacgta ctataaatac 1020 aaaggtgcga ttgatcaaac agtattaaca gtactaggta gtggttctaa atcttacatc 1080 caaccattga aagttgatga taaaaacggc tacttagcta aatcatatgc acaagtaaga 1140 aactatgtaa ctgagtcaat caatactggt aaagtattat atactttcta ccaaaaccca 1200 acattagtaa aaacagctat taaagctcaa gaaactgcat catcaatcaa aaatacatta 1260 agtaatttat tatcattctg gaaataa 1287 60 1053 DNA S. aureus 60 atgacaaaac attatttaaa cagtaagtat caatcagaac aacgttcatc agctatgaaa 60 aagattacaa tgggtacagc atctatcatt ttaggttccc ttgtatacat aggcgcagac 120 agccaacaag tcaatgcggc aacagaagct acgaacgcaa ctaataatca aagcacacaa 180 gtttctcaag caacatcaca accaattaat ttccaagtgc aaaaagatgg ctcttcagag 240 aagtcacaca tggatgacta tatgcaacac cctggtaaag taattaaaca aaataataaa 300 tattatttcc aaaccgtgtt aaacaatgca tcattctgga aagaatacaa attttacaat 360 gcaaacaatc aagaattagc aacaactgtt gttaacgata ataaaaaagc ggatactaga 420 acaatcaatg ttgcagttga acctggatat aagagcttaa ctactaaagt acatattgtc 480 gtgccacaaa ttaattacaa tcatagatat actacgcatt tggaatttga aaaagcaatt 540 cctacattag ctgacgcagc aaaaccaaac aatgttaaac cggttcaacc aaaaccagct 600 caacctaaaa cacctactga gcaaactaaa ccagttcaac ctaaagttga aaaagttaaa 660 cctactgtaa ctacaacaag caaagttgaa gacaatcact ctactaaagt tgtaagtact 720 gacacaacaa aagatcaaac taaaacacaa actgctcata cagttaaaac agcacaaact 780 gctcaagaac aaaataaagt tcaaacacct gttaaagatg ttgcaacagc gaaatctgaa 840 agcaacaatc aagctgtaag tgataataaa tcacaacaaa ctaacaaagt tacaaaacat 900 aacgaaacgc ctaaacaagc atctaaagct aaagaattac caaaaactgg tttaacttca 960 gttgataact ttattagcac agttgccttc gcaacacttg cccttttagg ttcattatct 1020 ttattacttt tcaaaagaaa agaatctaaa taa 1053 61 1938 DNA S. aureus 61 atgaacaaac agcaaaaaga atttaaatca ttttattcaa ttagaaagtc atcactaggc 60 gttgcatctg tagcgattag tacactttta ttattaatgt caaatggcga agcacaagca 120 gcagctgaag aaacaggtgg tacaaataca gaagcacaac caaaaactga agcagttgca 180 agtccaacaa caacatctga aaaagctcca gaaactaaac cagtagctaa tgctgtctca 240 gtatctaata aagaagttga ggcccctact tctgaaacaa aagaagctaa agaagttaaa 300 gaagttaaag cccctaagga aacaaaagca gttaaaccag cagcaaaagc cactaacaat 360 acatatccta ttttgaatca ggaacttaga gaagcgatta aaaaccctgc aataaaagat 420 aaagatcata gcgcaccaaa ctctcgtcca attgattttg aaatgaaaaa agaaaatggt 480 gagcaacaat tttatcatta tgccagctct gttaaacctg ctagagttat tttcactgat 540 tcaaaaccag aaattgaatt aggattacaa tcaggtcaat tttggagaaa atttgaagtt 600 tatgaaggtg acaaaaagtt gccaattaaa ttagtatcat acgatactgt taaagattac 660 gcttacattc gcttctctgt ttcaaatgga acaaaagccg ttaaaattgt aagttcaact 720 cacttcaata acaaagaaga aaaatacgat tacacattaa tggaattcgc acaaccaatt 780 tataacagtg cagataaatt caaaactgaa gaagattata aagctgaaaa attattagcg 840 ccatataaaa aagcgaaaac actagaaaga caagtttatg aattaaataa aattcaagat 900 aaacttcctg aaaaattaaa ggctgagtac aagaagaaat tagaggatac aaagaaagct 960 ttagatgagc aagtgaaatc agctattact gaattccaaa atgtacaacc aacaaatgaa 1020 aaaatgactg atttacaaga tacaaaatat gttgtttatg aaagtgttga gaataacgaa 1080 tctatgatgg atacttttgt taaacaccct attaaaacag gtatgcttaa cggcaaaaaa 1140 tatatggtca tggaaactac taatgacgat tactggaaag atttcatggt tgaaggtcaa 1200 cgtgttagaa ctataagcaa agatgctaaa aataatacta gaacaattat tttcccatat 1260 gttgaaggta aaactctata tgatgctatc gttaaagttc acgtaaaaac gattgattat 1320 gatggacaat accatgtcag aatcgttgat aaagaagcat ttacaaaagc caataccgat 1380 aaatctaaca aaaaagaaca acaagataac tcagctaaga aggaagctac tccagctacg 1440 cctagcaaac caacaccatc acctgttgaa aaagaatcac aaaaacaaga cagccaaaaa 1500 gatgacaata aacaattacc aagtgttgaa aaagaaaatg acgcatctag tgagtcaggt 1560 aaagacaaaa cgcctgctac aaaaccaact aaaggtgaag tagaatcaag tagtacaact 1620 ccaactaagg tagtatctac gactcaaaat gttgcaaaac caacaactgc ttcatcaaaa 1680 acaacaaaag atgttgttca aacttcagca ggttctagcg aagcaaaaga tagtgctcca 1740 ttacaaaaag caaacattaa aaacacaaat gatggacaca ctcaaagcca aaacaataaa 1800 aatacacaag aaaataaagc aaaatcatta ccacaaactg gtgaagaatc aaataaagat 1860 atgacattac cattaatggc attactagct ttaagtagca tcgttgcatt cgtattacct 1920 agaaaacgta aaaactaa 1938 62 2862 DNA S. aureus 62 atgaataata aaaagacagc aacaaataga aaaggcatga taccaaatcg attaaacaaa 60 ttttcgataa gaaagtattc tgtaggtact gcttcaattt tagtagggac aacattgatt 120 tttgggttaa gtggtcatga agctaaagcg gcagaacata cgaatggaga attaaatcaa 180 tcaaaaaatg aaacgacagc cccaagtgag aataaaacaa ctgaaaaagt tgatagtcgt 240 caactaaaag acaatacgca aactgcaact gcagatcagc ctaaagtgac aatgagtgat 300 agtgcaacag ttaaagaaac tagtagtaac atgcaatcac cacaaaacgc tacagctagt 360 caatctacta cacaaactag caatgtaaca acaaatgata aatcatcaac tacatatagt 420 aatgaaactg ataaaagtaa tttaacacaa gcaaaaaacg tttcaactac acctaaaaca 480 acgactatta aacaaagagc tttaaatcgc atggcagtga atactgttgc agctccacaa 540 caaggaacaa atgttaatga taaagtacat tttacgaaca ttgatattgc gattgataaa 600 ggacatgtta ataaaacaac aggaaatact gaattttggg caacttcaag tgatgtttta 660 aaattaaaag cgaattacac aatcgatgat tctgttaaag agggcgatac atttactttt 720 aaatatggtc aatatttccg tccaggttct gtaagattac cttcacaaac tcaaaattta 780 tataatgccc aaggtaatat tattgcaaaa ggtatttacg atagtaaaac aaatacaaca 840 acgtatactt ttacgaatta tgtagatcaa tacacaaatg ttagcggtag ctttgaacaa 900 gtcgcatttg cgaaacgtga aaatgcaaca actgataaaa ctgcttataa aatggaagta 960 actttaggta atgatacata tagtaaagat gtcattgtcg attatggtaa tcaaaaaggt 1020 caacaactta tttcgagtac aaattatatt aataatgaag atttgtcacg taatatgact 1080 gtttatgtaa atcaacctaa aaagacctat acaaaagaaa catttgtaac aaatttaact 1140 ggttataaat ttaatccaga tgctaaaaac ttcaaaattt acgaagtgac agatcaaaat 1200 caatttgtgg atagtttcac cccagatact tcaaaactta aagatgttac tggtcaattc 1260 gatgttattt atagtaatga taataagacg gcgacagtag atttattgaa tggtcaatct 1320 agtagtgata aacagtacat cattcaacaa gttgcttatc cagataatag ttcaacagat 1380 aatgggaaaa ttgattatac tttagaaaca caaaatggaa aaagtagttg gtcaaacagt 1440 tattcaaatg tgaatggctc atcaactgca aatggcgacc aaaagaaata taatctaggt 1500 gactatgtat gggaagatac aaataaagat ggtaaacaag atgccaatga aaaagggatt 1560 aaaggtgttt atgtcattct taaagatagt aacggtaaag aattagatcg tacgacaaca 1620 gatgaaaatg gtaaatatca gttcactggt ttaagcaatg gaacttatag tgtagagttt 1680 tcaacaccag ccggttatac accgacaact gcaaatgcag gtacagatga tgctgtagat 1740 tctgatggac taactacaac aggtgtcatt aaagacgctg acaacatgac attagatagt 1800 ggattctaca aaacaccaaa atatagttta ggtgattatg tttggtacga cagtaataaa 1860 gatggtaaac aagattcgac tgaaaaagga attaaaggtg ttaaagttac tttgcaaaac 1920 gaaaaaggcg aagtaattgg tacaactgaa acagatgaaa atggtaaata ccgctttgat 1980 aatttagata gtggtaaata caaagttatc tttgaaaagc ctgctggttt aactcaaaca 2040 ggtacaaata caactgaaga tgataaagat gccgatggtg gcgaagttga tgtaacaatt 2100 acggatcatg atgatttcac acttgataat ggctactacg aagaagaaac atcagatagt 2160 gactcagatt cggacagcga ttcagactca gatagcgact cagattcaga tagtgactca 2220 gactcagata gcgactcaga ctcagatagc gactcagaca gcgactcaga ctcagatagt 2280 gattcagatt cggacagcga ctcagattca gacagcgaat cagattcgga tagcgactca 2340 gactcagata gcgactcaga cagcgactca gattcagaca gtgactcaga ctcagacagc 2400 gactcagatt cagacagcga ttcagattcg gatagcgact cagattcaga tagcgattcg 2460 gactcagaca acgactcaga

ttctgacagc gattcagact cagatagcga ctcagattca 2520 gacagcgact cagattcaga cagcgattca gattcagata gcgattcaga ttcagacagc 2580 gactcagatt cagatagcga ctcagactca gacagcgatt cagactcaga tagcgactca 2640 gacagcgatt cagattcgga tagcgattca gattcagatg caggtaaaca tactccgact 2700 aaaccaatga gtacggttaa agatcagcat aaaacagcta aagcattacc agaaacaggt 2760 agtgaaaata ataattcaaa taatggcaca ttattcggtg gattattcgc ggcattagga 2820 tcattattgt tattcggtcg tcgtaaaaaa caaaataaat aa 2862 63 2808 DNA S. aureus 63 atgaatatga agaaaaaaga aaaacacgca attcggaaaa aatcgattgg cgtggcttca 60 gtgcttgtag gtacgttaat cggttttgga ctactcagca gtaaagaagc agatgcaagt 120 gaaaatagtg ttacgcaatc tgatagcgca agtaacgaaa gcaaaagtaa tgattcaagt 180 agcgttagtg ctgcacctaa aacagacgac acaaacgtga gtgatactaa aacatcgtca 240 aacactaata atggcgaaac gagtgtggcg caaaatccag cacaacagga aacgacacaa 300 tcatcatcaa caaatgcaac tacggaagaa acgccggtaa ctggtgaagc tactactacg 360 acaacgaatc aagctaatac accggcaaca actcaatcaa gcaatacaaa tgcggaggaa 420 ttagtgaatc aaacaagtaa tgaaacgact tctaatgata ctaatacagt atcatctgta 480 aattcacctc aaaattctac aaatgcggaa aatgtttcaa caacgcaaga tacttcaact 540 gaagcaacac cttcaaacaa tgaatcagct ccacagaata cagatgcaag taataaagat 600 gtagttagtc aagcggttaa tccaagtacg cctagaatga gagcatttag tttagcggca 660 gtagctgcag atgcaccggc agctggcaca gatattacga atcagttgac agatgtgaaa 720 gttactattg actctggtac gactgtgtat ccgcaccaag caggttatgt caaactgaat 780 tatggttttt cagtgcctaa ttctgctgtt aaaggtgaca cattcaaaat aactgtacct 840 aaagaattaa acttaaatgg tgtaacttca actgctaaag tgccaccaat tatggctgga 900 gatcaagtat tggcaaatgg tgtaatcgat agtgatggta atgttattta tacatttaca 960 gactatgttg ataataaaga aaatgtaaca gctaatatta ctatgccagc ttatattgac 1020 cctgaaaatg ttacaaagac aggtaatgtg acattgacaa ctggcatagg aaccaatact 1080 gctagtaaga cagtattaat cgactatgag aaatatggac aattccataa tttatcaatt 1140 aaaggtacga ttgatcaaat cgataaaaca aataatacgt atcgccaaac aatttatgtc 1200 aatccaagcg gagataacgt tgtgttacct gccttaacag gtaatttaat tcctaataca 1260 aagagtaatg cgttaataga tgcaaaaaac actgatatta aagtttatag agtcgataat 1320 gctaatgatt tatctgaaag ttattatgtg aatcctagcg attttgaaga tgtaactaat 1380 caagttagaa tttcatttcc aaatgctaat caatacaaag tagaatttcc tacggacgat 1440 gaccaaatta caacaccgta tattgtagtt gttaatggcc atattgatcc tgctagtaca 1500 ggtgatttag cactacgttc gacattttat ggttatgatt ctaattttat atggagatct 1560 atgtcatggg acaacgaagt agcatttaat aacggatcag gttctggtga cggtatcgat 1620 aaaccagttg ttcctgaaca acctgatgag cctggtgaaa ttgaaccaat tccagaggat 1680 tcagattctg acccaggttc agattctggc agcgattcta attcagatag cggttcagat 1740 tctggcagtg attctacatc agatagtggt tcagattcag cgagtgattc agattcagca 1800 agtgattcag actcagcgag tgattcagat tcagcaagtg attcagattc agcaagtgat 1860 tcagattcag caagtgattc agactcagca agtgattcag attcagcaag tgattcagat 1920 tcagcaagcg attcagattc agcgagcgat tcagattcag cgagcgattc agattcagcg 1980 agtgattccg actcagcgag cgattcagac tcagatagtg actcagattc cgatagcgat 2040 tccgactcag atagcgactc agattcagac agcgattctg actcagacag cgattctgac 2100 tcagacagtg actcagattc cgatagcgat tctgactcag acagtgactc agattccgat 2160 agcgattcag attcagacag tgattcagac tcagatagcg attcagattc cgacagtgac 2220 tcagactcag acagcgattc agattccgat agcgattcag attccgacag tgactcagat 2280 tccgatagtg actcggattc agcgagtgat tcagattcag atagcgattc agaatcagat 2340 agtgactcag actcagacag tgattcagat tcagatagtg actcagactc agacagcgat 2400 tcagaatcag atagtgactc cgattcagac agcgattcag aatcagatag tgactccgat 2460 tcagatagcg attcggattc agcgagtgat tcagactcag gtagtgactc cgattcatca 2520 agtgattcag attccgattc aacgagtgac acaggatcag acaacgactc agacagtgat 2580 tcaaatagcg attccgagtc aggttctaac aataatgtag ttccgcctaa ttcacctaaa 2640 aatggtacta atgcttctaa taaaaatgag gctaaagata gtaaagaacc attaccagat 2700 acaggttctg aagatgaagc gaatacgtca ctaatttggg gattattagc atcattaggt 2760 tcattactac ttttcagaag aaaaaaagaa aataaagata agaaataa 2808 64 3117 DNA S. aureus 64 gtgaaaaaca atcttaggta cggcattaga aaacataaat tgggagcagc atcagtattc 60 ttaggaacaa tgatcgttgt tgggatggga caagataaag aagctgcagc atcagaacaa 120 aagacaacta cagtagaaga aaatgggaat tcagctactg ataataaaac aagtgaaaca 180 caaacaactg ctactaacgt taatcatata gaagaaactc aatcatataa cgcaacagta 240 acagaacaac cgtcaaacgc aacacaagta acaactgaag aagcaccaaa agcagtacaa 300 gcaccacaaa ctgcacaacc agcaaatgta gaaacagtta aagaagaaga gaaacctcaa 360 gttaaggaaa cgacacaacc tcaagacaat agcggaaatc aaagacaagt agatttaaca 420 cctaaaaagg ttacacaaaa tcaagggaca gaaacacaag ttgaagtggc acagccaaga 480 acggcatcag aaagtaagcc acgtgtgaca agatcagcag atgtagcgga agctaaggaa 540 gctagtgacg tttcagaagt taaaggcaca gatgttacaa gtaaagttac agtagaaagt 600 ggttctattg aggcacctca aggaaataaa gtagagccac atgctggtca acgtgtcgta 660 ttgaaataca aattgaaatt cgcagatgga ttaaaaagag gagattattt tgattttaca 720 ttatcaaata atgtaaatac ttatggggtt tcaacagcta gaaaggtacc agagattaaa 780 aatggctcag ttgtaatggc tacaggtgag atcttaggga atggtaacat aagatataca 840 tttactaacg aaattgaaca caaggtagag gtaacagcta atttagaaat caacttattt 900 attgacccta aaactgtaca aagcaatgga gaacaaaaga ttacttctaa attaaatggt 960 gaagaaacag aaaaaacaat accagttgtt tataatccag gtgttagcaa tagttataca 1020 aatgtaaatg gatcaattga aacatttaat aaagaatcta ataaatttac acatatagct 1080 tatattaagc caatgaatgg aaaccagtca aacactgtat cagtaacagg gacgttgact 1140 gaaggtagta atttagctgg tggacaacct actgttaaag tatatgaata tctagggaaa 1200 aaagatgaat tgccacaaag tgtttatgca aatacatcag atactaacaa attcaaagat 1260 gtaacaaagg aaatgaatgg aaaattgagt gtgcaagaca atggtagtta ctcattgaat 1320 ttagataagt tggataaaac gtatgtcatt cattatacag gtgaatattt gcaagggtca 1380 gatcaggtta attttagaac tgaattatat gggtatccag aacgagcata taaatcttac 1440 tatgtttatg ggggatatcg tttaacttgg gataatggtt tagttttata tagcaataaa 1500 gctgacggca atggtaaaaa tggacaaatt attcaagata atgattttga atataaagaa 1560 gatactgcaa aaggaactat gagcgggcag tacgatgcca agcaaattat tgaaacagaa 1620 gaaaatcaag acaatacacc gcttgacatt gattaccaca cagctataga tggtgagggt 1680 ggttatgttg atgggtatat tgaaacaata gaagaaacgg attcatcagc tattgatatc 1740 gattaccata ctgctgtgga tagtgaagtg ggtcacgttg gaggatacac tgagtcctct 1800 gaggaatcaa atccaattga ctttgaagaa tcgacacatg aaaattcaaa acatcacgct 1860 gatgttgttg aatatgaaga ggatacaaat ccaggtggtg gccaagtaac aactgagtct 1920 aacttagttg aatttgacga agagtctaca aaaggtattg taactggcgc agtgagcgac 1980 catacaacaa ttgaagatac gaaagaatat acgactgaaa gtaatctgat tgaactagta 2040 gatgaactac ctgaagaaca tggtcaagca caaggaccaa tcgaggaaat tactgaaaac 2100 aatcatcata tttctcattc tggtttagga actgaaaatg gtcacggtaa ttatggcgtg 2160 attgaagaaa tcgaagaaaa tagccacgtt gatattaaga gtgaattagg ttacgaaggt 2220 ggccaaaata gcggtaacca gtcattcgag gaagacacag aagaagacaa acctaaatat 2280 gaacaaggtg gcaatatcgt agatatcgat ttcgacagtg tacctcaaat tcatggtcaa 2340 aataaaggtg accagtcatt cgaagaagat acagagaaag acaagcctaa atatgaacat 2400 ggcggtaata tcattgatat cgacttcgac agtgtgccac aaattcatgg attcaataag 2460 cataatgaaa ttattgaaga agatacaaac aaagataaac ctaattatca attcggtgga 2520 cacaatagtg ttgactttga agaagataca cttccaaaag taagcggcca aaatgaaggt 2580 caacaaacga ttgaagaaga tacaacgccg ccaacgccac cgacaccaga agtaccgagt 2640 gagccggaaa caccaatgcc accgacacca gaagtaccga gtgagccgga aacaccaacg 2700 ccaccaacac cagaggtacc aagtgagccg gaaacaccaa caccaccgac tccggaagta 2760 ccaagtgagc cggaaacacc aacaccaccg acaccagaag tgccgagtga gccagaaaca 2820 ccaacaccgc caacaccaga ggtaccagct gaacctggta aaccagtacc acccgcaaaa 2880 gaagaaccta aaaagccttc taaaccagtg gaacaaggta aagtagtaac acctgttatt 2940 gaaatcaatg aaaaggttaa agcagtggca ccaactaaaa aagcacaatc taagaaatct 3000 gaactacctg aaacaggtgg agaagaatca acaaacaaag gtatgttgtt cggcggatta 3060 ttcagcattc taggtttagc attattacgc agaaataaaa agaataacaa agcataa 3117 65 2634 DNA S. aureus 65 ttgaaaaaaa gaattgatta tttgtcgaat aagcagaata agtattcgat tagacgtttt 60 acagtaggta ccacatcagt aatagtaggg gcaactatac tatttgggat aggcaatcat 120 caagcacaag cttcagaaca atcgaacgat acaacgcaat cttcgaaaaa taatgcaagt 180 gcagattccg aaaaaaacaa tatgatagaa acacctcaat taaatacaac ggctaatgat 240 acatctgata ttagtgcaaa cacaaacagt gcgaatgtag atagcacaac aaaaccaatg 300 tctacacaaa cgagcaatac cactacaaca gagccagctt caacaaatga aacacctcaa 360 ccgacggcaa ttaaaaatca agcaactgct gcaaaaatgc aagatcaaac tgttcctcaa 420 gaagcaaatt ctcaagtaga taataaaaca acgaatgatg ctaatagcat agcaacaaac 480 agtgagctta aaaattctca aacattagat ttaccacaat catcaccaca aacgatttcc 540 aatgcgcaag gaactagtaa accaagtgtt agaacgagag ctgtacgtag tttagctgtt 600 gctgaaccgg tagtaaatgc tgctgatgct aaaggtacaa atgtaaatga taaagttacg 660 gcaagtaatt tcaagttaga aaagactaca tttgacccta atcaaagtgg taacacattt 720 atggcggcaa attttacagt gacagataaa gtgaaatcag gggattattt tacagcgaag 780 ttaccagata gtttaactgg taatggagac gtggattatt ctaattcaaa taatacgatg 840 ccaattgcag acattaaaag tacgaatggc gatgttgtag ctaaagcaac atatgatatc 900 ttgactaaga cgtatacatt tgtctttaca gattatgtaa ataataaaga aaatattaac 960 ggacaatttt cattaccttt atttacagac cgagcaaagg cacctaaatc aggaacatat 1020 gatgcgaata ttaatattgc ggatgaaatg tttaataata aaattactta taactatagt 1080 tcgccaattg caggaattga taaaccaaat ggcgcgaaca tttcttctca aattattggt 1140 gtagatacag cttcaggtca aaacacatac aagcaaacag tatttgttaa ccctaagcaa 1200 cgagttttag gtaatacgtg ggtgtatatt aaaggctacc aagataaaat cgaagaaagt 1260 agcggtaaag taagtgctac agatacaaaa ctgagaattt ttgaagtgaa tgatacatct 1320 aaattatcag atagctacta tgcagatcca aatgactcta accttaaaga agtaacagac 1380 caatttaaaa atagaatcta ttatgagcat ccaaatgtag ctagtattaa atttggtgat 1440 attactaaaa catatgtagt attagtagaa gggcattacg acaatacagg taagaactta 1500 aaaactcagg ttattcaaga aaatgttgat cctgtaacaa atagagacta cagtattttc 1560 ggttggaata atgagaatgt tgtacgttat ggtggtggaa gtgctgatgg tgattcagca 1620 gtaaatccga aagacccaac tccagggccg ccggttgacc cagaaccaag tccagaccca 1680 gaaccagaac caacgccaga tccagaacca agtccagacc cagaaccgga accaagccca 1740 gacccggatc cggattcgga ttcagacagt gactcaggct cagacagcga ctcaggttca 1800 gatagcgact cagaatcaga tagcgattcg gattcagaca gtgattcaga ttcagacagc 1860 gactcagaat cagatagcga ttcagaatca gatagcgact cagattcaga tagcgattca 1920 gattcagata gcgattcaga atcagatagc gattcggatt cagacagtga ttcagattca 1980 gacagcgact cagaatcaga tagcgactca gaatcagata gtgagtcaga ttcagacagt 2040 gactcggact cagacagtga ttcagactca gatagcgatt cagactcaga tagcgattca 2100 gactcagaca gcgattcaga ttcagacagc gactcagaat cagacagcga ctcagactca 2160 gatagcgact cagactcaga cagcgactca gattcagata gcgattcaga ctcagacagc 2220 gactcagact cagacagcga ctcagactca gatagcgatt cagactcaga cagcgactca 2280 gattcagata gcgattcgga ctcagacagc gattcagatt cagacagcga ctcagactcg 2340 gatagcgatt cagattcaga cagcgactca gactcggata gcgactcgga ttcagatagt 2400 gactccgatt caagagttac accaccaaat aatgaacaga aagcaccatc aaatcctaaa 2460 ggtgaagtaa accattctaa taaggtatca aaacaacaca aaactgatgc tttaccagaa 2520 acaggagata agagcgaaaa cacaaatgca actttatttg gtgcaatgat ggcattatta 2580 ggatcattac tattgtttag aaaacgcaag caagatcata aagaaaaagc gtaa 2634 66 1977 DNA S. aureus 66 atgaaaaagc aaataatttc gctaggcgca ttagcagttg catctagctt atttacatgg 60 gataacaaag cagatgcgat agtaacaaag gattatagta aagaatcaag agtgaatgag 120 aaaagtaaaa agggagctac tgtttcagat tattactatt ggaaaataat tgatagttta 180 gaggcacaat ttactggagc aatagactta ttggaagatt ataaatatgg agatcctatc 240 tataaagaag cgaaagatag attgatgaca agagtattag gagaagacca gtatttatta 300 aagaaaaaga ttgatgaata tgagctttat aaaaagtggt ataaaagttc aaataagaac 360 actaatatgc ttactttcca taaatataat ctttacaatt taacaatgaa tgaatataac 420 gatattttta actctttgaa agatgcagtt tatcaattta ataaagaagt taaagaaata 480 gagcataaaa atgttgactt gaagcagttt gataaagatg gagaagacaa ggcaactaaa 540 gaagtttatg accttgtttc tgaaattgat acattagttg taacttatta tgctgataag 600 gattatgggg agcatgcgaa agagttacga gcaaaactgg acttaatcct tggagataca 660 gacaatccac ataaaattac aaatgagcgt ataaaaaaag aaatgatcga tgacttaaat 720 tcaattatag atgatttctt tatggagact aaacaaaata gaccgaattc tataacaaaa 780 tatgatccaa caaaacacaa ttttaaagag aagagtgaaa ataaacctaa ttttgataaa 840 ttagttgaag aaacaaaaaa agcagttaaa gaagcagacg aatcttggaa aaataaaact 900 gtcaaaaaat acgaggaaac tgtaacaaaa tctcctgttg taaaagaaga gaagaaagtt 960 gaagaacctc aattacctaa agttggaaac cagcaagagg ttaaaactac ggctggtaaa 1020 gctgaagaaa caacacaacc agtggcacag ccattagtaa aaattccaca agaaacaatc 1080 tatggtgaaa ctgtaaaagg tccagaatat ccaacgatgg aaaataaaac gttacaaggt 1140 gaaatcgttc aaggtcccga ttttctaaca atggaacaaa acagaccatc tttaagcgat 1200 aattatactc aaccgacgac accgaaccct attttagaag gtcttgaagg tagctcatct 1260 aaacttgaaa taaaaccaca aggtactgaa tcaacgttga aaggtattca aggagaatca 1320 agtgatattg aagttaaacc tcaagcaact gaaacaacag aagcttctca atatggtccg 1380 agaccgcaat ttaacaaaac acctaagtat gtgaaatata gagatgctgg tacaggtatc 1440 cgtgaataca acgatggaac atttggatat gaagcgagac caagattcaa caagccaagt 1500 gaaacaaatg catacaacgt aacgacaaat caagatggca cagtatcata cggagctcgc 1560 ccaacacaaa acaagccaag tgaaacaaac gcatataacg taacaacaca tgcaaatggt 1620 caagtatcat acggtgctcg cccaacacaa aaaaagccaa gcaaaacaaa tgcatacaac 1680 gtaacaacac atgcaaatgg tcaagtatca tatggcgctc gcccgacaca aaaaaagcca 1740 agcaaaacaa atgcatataa cgtaacaaca catgcaaatg gtcaagtatc atacggagct 1800 cgcccgacat acaagaagcc aagcgaaaca aatgcataca acgtaacaac acatgcaaat 1860 ggtcaagtat catatggcgc tcgcccgaca caaaaaaagc caagcgaaac aaacgcatat 1920 aacgtaacaa cacatgcaga tggtactgcg acatatgggc ctagagtaac aaaataa 1977 67 961 PRT S. aureus 67 Met Lys Ser Asn Leu Arg Tyr Gly Ile Arg Lys His Lys Leu Gly Ala 1 5 10 15 Ala Ser Val Phe Leu Gly Thr Met Ile Val Val Gly Met Gly Gln Glu 20 25 30 Lys Glu Ala Ala Ala Ser Glu Gln Asn Asn Thr Thr Val Glu Glu Ser 35 40 45 Gly Ser Ser Ala Thr Glu Ser Lys Ala Ser Glu Thr Gln Thr Thr Thr 50 55 60 Asn Asn Val Asn Thr Ile Asp Glu Thr Gln Ser Tyr Ser Ala Thr Ser 65 70 75 80 Thr Glu Gln Pro Ser Lys Ser Thr Gln Val Thr Thr Glu Glu Ala Pro 85 90 95 Thr Thr Val Gln Ala Pro Lys Val Glu Thr Glu Met Lys Ser Gln Glu 100 105 110 Asp Leu Pro Ser Glu Lys Val Ala Asp Lys Glu Thr Thr Gly Thr Gln 115 120 125 Val Asp Ile Ala Gln Pro Ser Asn Val Ser Glu Ile Lys Pro Arg Met 130 135 140 Lys Arg Ser Ala Asp Val Thr Ala Val Ser Glu Lys Glu Val Ala Glu 145 150 155 160 Glu Ala Lys Ala Thr Gly Thr Asp Val Thr Asn Lys Val Glu Val Thr 165 170 175 Glu Ser Ser Leu Glu Gly His Asn Lys Asp Ser Asn Ile Val Asn Pro 180 185 190 His Asn Ala Gln Arg Val Thr Leu Lys Tyr Lys Trp Lys Phe Gly Glu 195 200 205 Gly Ile Lys Ala Gly Asp Tyr Phe Asp Phe Thr Leu Ser Asp Asn Val 210 215 220 Glu Thr His Gly Ile Ser Thr Leu Arg Lys Val Pro Glu Ile Lys Ser 225 230 235 240 Ser Thr Glu Asp Lys Val Met Ala Asn Gly Gln Val Ile Asn Glu Arg 245 250 255 Thr Ile Arg Tyr Thr Phe Thr Asp Tyr Ile Asn Asn Lys Lys Asp Leu 260 265 270 Thr Ala Glu Leu Asn Leu Asn Leu Phe Ile Asp Pro Thr Thr Val Thr 275 280 285 Lys Gln Gly Ser Gln Lys Val Glu Val Thr Leu Gly Gln Asn Lys Val 290 295 300 Ser Lys Glu Phe Asp Ile Lys Tyr Leu Asp Gly Val Lys Asp Arg Met 305 310 315 320 Gly Val Thr Val Asn Gly Arg Ile Asp Thr Leu Asn Lys Glu Glu Gly 325 330 335 Lys Phe Ser His Phe Ala Tyr Val Lys Pro Asn Asn Gln Ser Leu Thr 340 345 350 Ser Val Thr Val Thr Gly Gln Val Thr Ser Gly Tyr Lys Gln Ser Ala 355 360 365 Asn Asn Pro Thr Val Lys Val Tyr Lys His Ile Gly Ser Asp Glu Leu 370 375 380 Ala Glu Ser Val Tyr Ala Lys Leu Asp Asp Thr Ser Lys Phe Glu Asp 385 390 395 400 Val Thr Glu Lys Val Asn Leu Ser Tyr Thr Ser Asn Gly Gly Tyr Thr 405 410 415 Leu Asn Leu Gly Asp Leu Asp Asn Ser Lys Asp Tyr Val Ile Lys Tyr 420 425 430 Glu Gly Glu Tyr Asp Gln Asn Ala Lys Asp Leu Asn Phe Arg Thr His 435 440 445 Leu Ser Gly Tyr His Lys Tyr Tyr Pro Tyr Tyr Pro Tyr Tyr Pro Tyr 450 455 460 Tyr Pro Val Gln Leu Thr Trp Asn Asn Gly Val Ala Phe Tyr Ser Asn 465 470 475 480 Asn Ala Lys Gly Asp Gly Lys Asp Lys Pro Asn Asp Pro Ile Ile Glu 485 490 495 Lys Ser Glu Pro Ile Asp Leu Asp Ile Lys Ser Glu Pro Pro Val Glu 500 505 510 Lys His Glu Leu Thr Gly Thr Ile Glu Glu Ser Asn Asp Ser Lys Pro 515 520 525 Ile Asp Phe Glu Tyr His Thr Ala Val Glu Gly Ala Glu Gly His Ala 530 535 540 Glu Gly Ile Ile Glu Thr Glu Glu Asp Ser Ile His Val Asp Phe Glu 545 550 555 560 Glu Ser Thr His Glu Asn Ser Lys His His Ala Asp Val Val Glu Tyr 565 570 575 Glu Glu Asp Thr Asn Pro Gly Gly Gly Gln Val Thr Thr Glu Ser Asn 580 585 590 Leu Val Glu Phe Asp Glu Glu Ser Thr Lys Gly Ile Val Thr Gly Ala 595 600 605 Val Ser Asp His Thr Thr Val Glu Asp Thr Lys Glu Tyr Thr Thr Glu 610 615 620 Ser Asn Leu Ile Glu Leu Val Asp Glu Leu Pro Glu Glu His Gly Gln 625 630 635 640 Ala Gln Gly Pro Ile Glu Glu Ile Thr Glu Asn Asn His His

Ile Ser 645 650 655 His Ser Gly Leu Gly Thr Glu Asn Gly His Gly Asn Tyr Gly Val Ile 660 665 670 Asp Glu Ile Glu Glu Asn Ser His Val Asp Ile Lys Ser Glu Leu Gly 675 680 685 Tyr Glu Gly Gly Gln Asn Ser Gly Asn Gln Ser Phe Glu Glu Asp Thr 690 695 700 Glu Glu Asp Lys Pro Lys Tyr Glu Gln Gly Gly Asn Ile Val Asp Ile 705 710 715 720 Asp Phe Asp Ser Val Pro Gln Ile His Gly Gln Asn Asn Gly Asn Gln 725 730 735 Ser Phe Glu Glu Asp Thr Glu Glu Asp Lys Pro Lys Tyr Glu Gln Gly 740 745 750 Gly Asn Ile Ile Asp Ile Asp Phe Asp Ser Val Pro Gln Ile His Gly 755 760 765 Phe Asn Lys His Asn Glu Ile Ile Glu Glu Asp Thr Asn Lys Asp Lys 770 775 780 Pro Asn Tyr Gln Phe Gly Gly His Asn Ser Val Asp Phe Glu Glu Asp 785 790 795 800 Thr Leu Pro Lys Val Ser Gly Gln Asn Glu Gly Gln Gln Thr Ile Glu 805 810 815 Glu Asp Thr Thr Pro Pro Thr Pro Pro Thr Pro Glu Val Pro Ser Glu 820 825 830 Pro Glu Thr Pro Thr Pro Pro Thr Pro Glu Val Pro Ser Glu Pro Gly 835 840 845 Glu Pro Thr Pro Pro Lys Pro Glu Val Pro Ser Glu Pro Glu Thr Pro 850 855 860 Val Pro Pro Thr Pro Glu Val Pro Ser Glu Pro Gly Lys Pro Val Pro 865 870 875 880 Pro Ala Lys Glu Glu Pro Lys Lys Pro Ser Lys Pro Val Glu Gln Gly 885 890 895 Lys Val Val Thr Pro Val Ile Glu Ile Asn Glu Lys Val Lys Ala Val 900 905 910 Ala Pro Thr Lys Gln Lys Gln Ser Lys Lys Ser Glu Leu Pro Glu Thr 915 920 925 Gly Gly Glu Glu Ser Thr Asn Lys Gly Met Leu Phe Gly Gly Leu Phe 930 935 940 Ser Ile Leu Gly Leu Val Leu Leu Arg Arg Asn Lys Lys Asn Asn Lys 945 950 955 960 Ala 68 578 PRT S. aureus 68 Met Lys Phe Lys Ser Leu Ile Thr Thr Thr Leu Ala Leu Gly Val Ile 1 5 10 15 Ala Ser Thr Gly Ala Asn Phe Asn Thr Asn Glu Ala Ser Ala Ala Ala 20 25 30 Lys Pro Leu Asp Lys Ser Ser Ser Thr Leu His His Gly His Ser Asn 35 40 45 Ile Gln Ile Pro Tyr Thr Ile Thr Val Asn Gly Thr Ser Gln Asn Ile 50 55 60 Leu Ser Ser Leu Thr Phe Asn Lys Asn Gln Asn Ile Ser Tyr Lys Asp 65 70 75 80 Ile Glu Asn Lys Val Lys Ser Val Leu Tyr Phe Asn Arg Gly Ile Ser 85 90 95 Asp Ile Asp Leu Arg Leu Ser Lys Gln Ala Glu Tyr Thr Val His Phe 100 105 110 Lys Asn Gly Thr Lys Arg Val Ile Asp Leu Lys Ser Gly Ile Tyr Thr 115 120 125 Ala Asp Leu Ile Asn Thr Ser Asp Ile Lys Ala Ile Ser Val Asn Val 130 135 140 Asp Thr Lys Lys Gln Pro Lys Asp Lys Ala Lys Ala Asn Val Gln Val 145 150 155 160 Pro Tyr Thr Ile Thr Val Asn Gly Thr Ser Gln Asn Ile Leu Ser Asn 165 170 175 Leu Thr Phe Asn Lys Asn Gln Asn Ile Ser Tyr Lys Asp Leu Glu Gly 180 185 190 Lys Val Lys Ser Val Leu Glu Ser Asn Arg Gly Ile Thr Asp Val Asp 195 200 205 Leu Arg Leu Ser Lys Gln Ala Lys Tyr Thr Val Asn Phe Lys Asn Gly 210 215 220 Thr Lys Lys Val Ile Asp Leu Lys Ser Gly Ile Tyr Thr Ala Asn Leu 225 230 235 240 Ile Asn Ser Ser Asp Ile Lys Ser Ile Asn Ile Asn Val Asp Thr Lys 245 250 255 Lys His Ile Glu Asn Lys Ala Lys Arg Asn Tyr Gln Val Pro Tyr Ser 260 265 270 Ile Asn Leu Asn Gly Thr Ser Thr Asn Ile Leu Ser Asn Leu Ser Phe 275 280 285 Ser Asn Lys Pro Trp Thr Asn Tyr Lys Asn Leu Thr Ser Gln Ile Lys 290 295 300 Ser Val Leu Lys His Asp Arg Gly Ile Ser Glu Gln Asp Leu Lys Tyr 305 310 315 320 Ala Lys Lys Ala Tyr Tyr Thr Val Tyr Phe Lys Asn Gly Gly Lys Arg 325 330 335 Ile Leu Gln Leu Asn Ser Lys Asn Tyr Thr Ala Asn Leu Val His Ala 340 345 350 Lys Asp Val Lys Arg Ile Glu Ile Thr Val Lys Thr Gly Thr Lys Ala 355 360 365 Lys Ala Asp Arg Tyr Val Pro Tyr Thr Ile Ala Val Asn Gly Thr Ser 370 375 380 Thr Pro Ile Leu Ser Lys Leu Lys Ile Ser Asn Lys Gln Leu Ile Ser 385 390 395 400 Tyr Lys Tyr Leu Asn Asp Lys Val Lys Ser Val Leu Lys Ser Glu Arg 405 410 415 Gly Ile Ser Asp Leu Asp Leu Lys Phe Ala Lys Gln Ala Lys Tyr Thr 420 425 430 Val Tyr Phe Lys Asn Gly Lys Lys Gln Val Val Asn Leu Lys Ser Asp 435 440 445 Ile Phe Thr Pro Asn Leu Phe Ser Ala Lys Asp Ile Lys Lys Ile Asp 450 455 460 Ile Asp Val Lys Gln Tyr Thr Lys Ser Lys Lys Lys Ile Asn Lys Ser 465 470 475 480 Asn Asn Val Lys Phe Pro Val Thr Ile Asn Lys Phe Glu Asn Ile Val 485 490 495 Ser Asn Glu Phe Val Phe Tyr Asn Ala Ser Lys Ile Thr Ile Asn Asp 500 505 510 Leu Ser Ile Lys Leu Lys Ser Ala Met Ala Asn Asp Gln Gly Ile Thr 515 520 525 Lys His Asp Ile Gly Leu Ala Glu Arg Ala Val Tyr Lys Val Tyr Phe 530 535 540 Lys Asn Gly Ser Ser Lys Tyr Val Asp Leu Lys Thr Glu Tyr Lys Asp 545 550 555 560 Glu Arg Val Phe Lys Ala Thr Asp Ile Lys Lys Val Asp Ile Glu Leu 565 570 575 Lys Phe 69 995 PRT S. aureus 69 Met Asn Asn Lys Lys Thr Ala Thr Asn Arg Lys Gly Met Ile Pro Asn 1 5 10 15 Arg Leu Asn Lys Phe Ser Ile Arg Lys Tyr Ser Val Gly Thr Ala Ser 20 25 30 Ile Leu Val Gly Thr Thr Leu Ile Phe Gly Leu Ser Gly His Glu Ala 35 40 45 Lys Ala Ala Glu His Thr Asn Gly Glu Leu Asn Gln Ser Lys Asn Glu 50 55 60 Thr Thr Ala Pro Ser Glu Asn Lys Thr Thr Lys Lys Val Asp Ser Arg 65 70 75 80 Gln Leu Lys Asp Asn Thr Gln Thr Ala Thr Ala Asp Gln Pro Lys Val 85 90 95 Thr Met Ser Asp Ser Ala Thr Val Lys Glu Thr Ser Ser Asn Met Gln 100 105 110 Ser Pro Gln Asn Ala Thr Ala Asn Gln Ser Thr Thr Lys Thr Ser Asn 115 120 125 Val Thr Thr Asn Asp Lys Ser Ser Thr Thr Tyr Ser Asn Glu Thr Asp 130 135 140 Lys Ser Asn Leu Thr Gln Ala Lys Asp Val Ser Thr Thr Pro Lys Thr 145 150 155 160 Thr Thr Ile Lys Pro Arg Thr Leu Asn Arg Met Ala Val Asn Thr Val 165 170 175 Ala Ala Pro Gln Gln Gly Thr Asn Val Asn Asp Lys Val His Phe Ser 180 185 190 Asn Ile Asp Ile Ala Ile Asp Lys Gly His Val Asn Gln Thr Thr Gly 195 200 205 Lys Thr Glu Phe Trp Ala Thr Ser Ser Asp Val Leu Lys Leu Lys Ala 210 215 220 Asn Tyr Thr Ile Asp Asp Ser Val Lys Glu Gly Asp Thr Phe Thr Phe 225 230 235 240 Lys Tyr Gly Gln Tyr Phe Arg Pro Gly Ser Val Arg Leu Pro Ser Gln 245 250 255 Thr Gln Asn Leu Tyr Asn Ala Gln Gly Asn Ile Ile Ala Lys Gly Ile 260 265 270 Tyr Asp Ser Thr Thr Asn Thr Thr Thr Tyr Thr Phe Thr Asn Tyr Val 275 280 285 Asp Gln Tyr Thr Asn Val Arg Gly Ser Phe Glu Gln Val Ala Phe Ala 290 295 300 Lys Arg Lys Asn Ala Thr Thr Asp Lys Thr Ala Tyr Lys Met Glu Val 305 310 315 320 Thr Leu Gly Asn Asp Thr Tyr Ser Glu Glu Ile Ile Val Asp Tyr Gly 325 330 335 Asn Lys Lys Ala Gln Pro Leu Ile Ser Ser Thr Asn Tyr Ile Asn Asn 340 345 350 Glu Asp Leu Ser Arg Asn Met Thr Ala Tyr Val Asn Gln Pro Lys Asn 355 360 365 Thr Tyr Thr Lys Gln Thr Phe Val Thr Asn Leu Thr Gly Tyr Lys Phe 370 375 380 Asn Pro Asn Ala Lys Asn Phe Lys Ile Tyr Glu Val Thr Asp Gln Asn 385 390 395 400 Gln Phe Val Asp Ser Phe Thr Pro Asp Thr Ser Lys Leu Lys Asp Val 405 410 415 Thr Asp Gln Phe Asp Val Ile Tyr Ser Asn Asp Asn Lys Thr Ala Thr 420 425 430 Val Asp Leu Met Lys Gly Gln Thr Ser Ser Asn Lys Gln Tyr Ile Ile 435 440 445 Gln Gln Val Ala Tyr Pro Asp Asn Ser Ser Thr Asp Asn Gly Lys Ile 450 455 460 Asp Tyr Thr Leu Asp Thr Asp Lys Thr Lys Tyr Ser Trp Ser Asn Ser 465 470 475 480 Tyr Ser Asn Val Asn Gly Ser Ser Thr Ala Asn Gly Asp Gln Lys Lys 485 490 495 Tyr Asn Leu Gly Asp Tyr Val Trp Glu Asp Thr Asn Lys Asp Gly Lys 500 505 510 Gln Asp Ala Asn Glu Lys Gly Ile Lys Gly Val Tyr Val Ile Leu Lys 515 520 525 Asp Ser Asn Gly Lys Glu Leu Asp Arg Thr Thr Thr Asp Glu Asn Gly 530 535 540 Lys Tyr Gln Phe Thr Gly Leu Ser Asn Gly Thr Tyr Ser Val Glu Phe 545 550 555 560 Ser Thr Pro Ala Gly Tyr Thr Pro Thr Thr Ala Asn Val Gly Thr Asp 565 570 575 Asp Ala Val Asp Ser Asp Gly Leu Thr Thr Thr Gly Val Ile Lys Asp 580 585 590 Ala Asp Asn Met Thr Leu Asp Ser Gly Phe Tyr Lys Thr Pro Lys Tyr 595 600 605 Ser Leu Gly Asp Tyr Val Trp Tyr Asp Ser Asn Lys Asp Gly Lys Gln 610 615 620 Asp Ser Thr Glu Lys Gly Ile Lys Gly Val Lys Val Thr Leu Gln Asn 625 630 635 640 Glu Lys Gly Glu Val Ile Gly Thr Thr Glu Thr Asp Glu Asn Gly Lys 645 650 655 Tyr Arg Phe Asp Asn Leu Asp Ser Gly Lys Tyr Lys Val Ile Phe Glu 660 665 670 Lys Pro Ala Gly Leu Thr Gln Thr Gly Thr Asn Thr Thr Glu Asp Asp 675 680 685 Lys Asp Ala Asp Gly Gly Glu Val Asp Val Thr Ile Thr Asp His Asp 690 695 700 Asp Phe Thr Leu Asp Asn Gly Tyr Tyr Glu Glu Glu Thr Ser Asp Ser 705 710 715 720 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 725 730 735 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 740 745 750 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 755 760 765 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 770 775 780 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 785 790 795 800 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 805 810 815 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 820 825 830 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 835 840 845 Asp Ser Asp Ser Asp Ser Asp Ser Asp Asn Asp Ser Asp Ser Asp Ser 850 855 860 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 865 870 875 880 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 885 890 895 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 900 905 910 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Asn Asp Ser Asp Ser 915 920 925 Asp Ser Asp Ser Asp Ser Asp Ala Gly Lys His Thr Pro Ala Lys Pro 930 935 940 Met Ser Thr Val Lys Asp Gln His Lys Thr Ala Lys Ala Leu Pro Glu 945 950 955 960 Thr Gly Ser Glu Asn Asn Asn Ser Asn Asn Gly Thr Leu Phe Gly Gly 965 970 975 Leu Phe Ala Ala Leu Gly Ser Leu Leu Leu Phe Gly Arg Arg Lys Lys 980 985 990 Gln Asn Lys 995 70 773 PRT S. aureus 70 Glu Glu Asn Ser Val Gln Asp Val Lys Asp Ser Asn Thr Asp Asp Glu 1 5 10 15 Leu Ser Asp Ser Asn Asp Gln Ser Ser Asp Glu Glu Lys Asn Asp Val 20 25 30 Ile Asn Asn Asn Gln Ser Ile Asn Thr Asp Asp Asn Asn Gln Ile Ile 35 40 45 Lys Lys Glu Glu Thr Asn Asn Tyr Asp Gly Ile Glu Lys Arg Ser Glu 50 55 60 Asp Arg Thr Glu Ser Thr Thr Asn Val Asp Glu Asn Glu Ala Thr Phe 65 70 75 80 Leu Gln Lys Thr Pro Gln Asp Asn Thr His Leu Thr Glu Glu Glu Val 85 90 95 Lys Glu Ser Ser Ser Val Glu Ser Ser Asn Ser Ser Ile Asp Thr Ala 100 105 110 Gln Gln Pro Ser His Thr Thr Ile Asn Arg Glu Glu Ser Val Gln Thr 115 120 125 Ser Asp Asn Val Glu Asp Ser His Val Ser Asp Phe Ala Asn Ser Lys 130 135 140 Ile Lys Glu Ser Asn Thr Glu Ser Gly Lys Glu Glu Asn Thr Ile Glu 145 150 155 160 Gln Pro Asn Lys Val Lys Glu Asp Ser Thr Thr Ser Gln Pro Ser Gly 165 170 175 Tyr Thr Asn Ile Asp Glu Lys Ile Ser Asn Gln Asp Glu Leu Leu Asn 180 185 190 Leu Pro Ile Asn Glu Tyr Glu Asn Lys Ala Arg Pro Leu Ser Thr Thr 195 200 205 Ser Ala Gln Pro Ser Ile Lys Arg Val Thr Val Asn Gln Leu Ala Ala 210 215 220 Glu Gln Gly Ser Asn Val Asn His Leu Ile Lys Val Thr Asp Gln Ser 225 230 235 240 Ile Thr Glu Gly Tyr Asp Asp Ser Glu Gly Val Ile Lys Ala His Asp 245 250 255 Ala Glu Asn Leu Ile Tyr Asp Val Thr Phe Glu Val Asp Asp Lys Val 260 265 270 Lys Ser Gly Asp Thr Met Thr Val Asp Ile Asp Lys Asn Thr Val Pro 275 280 285 Ser Asp Leu Thr Asp Ser Phe Thr Ile Pro Lys Ile Lys Asp Asn Ser 290 295 300 Gly Glu Ile Ile Ala Thr Gly Thr Tyr Asp Asn Lys Asn Lys Gln Ile 305 310 315 320 Thr Tyr Thr Phe Thr Asp Tyr Val Asp Lys Tyr Glu Asn Ile Lys Ala 325 330 335 His Leu Lys Leu Thr Ser Tyr Ile Asp Lys Ser Lys Val Pro Asn Asn 340 345 350 Asn Thr Lys Leu Asp Val Glu Tyr Lys Thr Ala Leu Ser Ser Val Asn 355 360 365 Lys Thr Ile Thr Val Glu Tyr Gln Arg Pro Asn Glu Asn Arg Thr Ala 370 375 380 Asn Leu Gln Ser Met Phe Thr Asn Ile Asp Thr Lys Asn His Thr Val 385 390 395 400 Glu Gln Thr Ile Tyr Ile Asn Pro Leu Arg Tyr Ser Ala Lys Glu Thr 405 410 415 Asn Val Asn Ile Ser Gly Asn Gly Asp Glu Gly Ser Thr Ile Ile Asp 420 425 430 Asp Ser Thr Ile Ile Lys Val Tyr Lys Val Gly Asp Asn Gln Asn Leu 435 440 445 Pro Asp Ser Asn Arg Ile Tyr Asp Tyr Ser Glu Tyr Glu Asp Val Thr 450 455 460 Asn Asp Asp Tyr Ala Gln Leu Gly Asn Asn Asn Asp Val Asn Ile Asn 465 470 475 480 Phe Gly Asn Ile Asp Ser Pro Tyr Ile Ile Lys Val Ile Ser Lys Tyr 485 490 495 Asp Pro Asn Lys Asp Asp Tyr Thr Thr Ile Gln Gln Thr Val Thr Met 500 505 510 Gln Thr Thr Ile Asn Glu Tyr Thr Gly Glu Phe Arg Thr Ala Ser Tyr 515 520 525 Asp Asn Thr Ile Ala Phe Ser Thr Ser Ser Gly Gln Gly Gln Gly Asp 530 535 540 Leu Pro Pro Glu Lys Thr Tyr Lys Ile Gly Asp Tyr Val Trp Glu Asp 545

550 555 560 Val Asp Lys Asp Gly Ile Gln Asn Thr Asn Asp Asn Glu Lys Pro Leu 565 570 575 Ser Asn Val Leu Val Thr Leu Thr Tyr Pro Asp Gly Thr Ser Lys Ser 580 585 590 Val Arg Thr Asp Glu Asp Gly Lys Tyr Gln Phe Asp Gly Leu Lys Asn 595 600 605 Gly Leu Thr Tyr Lys Ile Thr Phe Glu Thr Pro Glu Gly Tyr Thr Pro 610 615 620 Thr Leu Lys His Ser Gly Thr Asn Pro Ala Leu Asp Ser Glu Gly Asn 625 630 635 640 Ser Val Trp Val Thr Ile Asn Gly Gln Asp Asp Met Thr Ile Asp Ser 645 650 655 Gly Phe Tyr Gln Thr Pro Lys Tyr Ser Leu Gly Asn Tyr Val Trp Tyr 660 665 670 Asp Thr Asn Lys Asp Gly Ile Gln Gly Asp Asp Glu Lys Gly Ile Ser 675 680 685 Gly Val Lys Val Thr Leu Lys Asp Glu Asn Gly Asn Ile Ile Ser Thr 690 695 700 Thr Thr Thr Asp Glu Asn Gly Lys Tyr Gln Phe Asp Asn Leu Asn Ser 705 710 715 720 Gly Asn Tyr Ile Val His Phe Asp Lys Pro Ser Gly Met Thr Gln Thr 725 730 735 Thr Thr Asp Ser Gly Asp Asp Asp Glu Gln Asp Ala Asp Gly Glu Glu 740 745 750 Val His Val Thr Ile Thr Asp His Asp Asp Phe Ser Ile Asp Asn Gly 755 760 765 Tyr Tyr Asp Asp Glu 770 71 2886 DNA S. aureus 71 gtgaaaagca atcttagata cggcataaga aaacacaaat tgggagcggc ctcagtattc 60 ttaggaacaa tgatcgttgt tggaatggga caagaaaaag aagctgcagc atcggaacaa 120 aacaatacta cagtagagga aagtgggagt tcagctactg aaagtaaagc aagcgaaaca 180 caaacaacta caaataacgt taatacaata gatgaaacac aatcatacag cgcgacatca 240 actgagcaac catcaaaatc aactcaagta acaacagaag aagcaccaac aactgtgcaa 300 gcaccaaaag tagaaaccga aatgaaatca caagaagatt taccatcaga aaaagttgct 360 gataaggaaa ctacaggaac tcaagttgac atagctcaac caagtaacgt ctcagaaatt 420 aaaccaagaa tgaaaagatc agctgacgtt acagcagttt cagagaaaga agtagcggaa 480 gaagctaaag cgacaggtac agatgtaaca aataaagtgg aagttactga aagctcttta 540 gaaggacata ataaagattc gaatattgtt aatccgcata atgctcaaag agtaacttta 600 aaatacaaat ggaaatttgg agaaggaatt aaggcaggag attattttga tttcacatta 660 agtgataatg ttgaaacaca tggtatatca acactgcgta aagttccgga gataaaaagt 720 tcaacagaag ataaagttat ggcaaatggt caagttataa atgaacgtac aattcgctat 780 acatttactg attatataaa taacaaaaaa gatttaactg ctgaattaaa cttaaaccta 840 ttcattgacc caacaacagt gacaaagcaa gggagtcaaa aagttgaagt aacactaggt 900 caaaataaag tctcaaaaga atttgatatc aaatatttag acggcgttaa agatagaatg 960 ggtgttactg ttaatggtcg tattgatact ttgaataaag aagagggtaa atttagccat 1020 tttgcatatg tgaagcctaa caaccagtcg ttaacttctg tcacagtaac tggtcaagta 1080 acatctggat ataaacaaag tgctaataat ccaacagtca aagtatataa acacattggt 1140 tcagatgaat tagctgaaag tgtttatgca aagcttgatg ataccagtaa atttgaagat 1200 gtgactgaaa aagtaaatct atcttacaca agtaatggtg ggtacacatt gaaccttggc 1260 gatttagata attcgaaaga ctatgtaatt aaatatgaag gtgaatatga tcaaaatgct 1320 aaggatctaa atttccgaac acatctttca ggatatcata aatactaccc atactatcct 1380 tattacccgt attatccagt tcaattaact tggaacaacg gtgttgcatt ttactctaat 1440 aatgctaaag gcgatggtaa agataaacca aatgatccta tcattgagaa gagtgaacca 1500 attgatttag acattaaatc agagccacca gtggagaagc atgaattgac tggtacaatc 1560 gaagaaagta acgattctaa gccaattgat tttgaatatc atacagctgt tgaaggtgca 1620 gaaggtcatg cagaaggtat tattgaaact gaagaagatt ctattcatgt ggattttgaa 1680 gaatctacac atgaaaattc aaaacatcac gctgatgttg ttgaatatga agaggataca 1740 aacccaggtg gtggccaagt aacaactgag tctaacttag ttgaatttga cgaagagtct 1800 acaaaaggta ttgtaactgg cgcagtgagc gaccatacaa cagttgaaga tacgaaagaa 1860 tatacaactg aaagtaatct gattgaatta gtggatgaat tacctgaaga acatggtcaa 1920 gcacaagggc caatcgagga aattactgaa aacaatcatc atatttctca ttctggttta 1980 ggaactgaaa atggtcacgg taattatggc gtgattgatg aaatcgaaga aaatagccac 2040 gttgatatta agagtgaatt aggttatgaa ggtggccaaa atagcggtaa tcagtcattc 2100 gaggaagaca cagaagaaga taaacctaaa tatgaacaag gtggtaatat cgtagatatc 2160 gatttcgaca gtgtacctca aattcatggt caaaataatg gtaaccagtc attcgaggaa 2220 gacacagaag aagacaagcc taagtatgaa caaggtggta acatcattga tatcgacttc 2280 gacagtgtgc cacaaattca tggattcaat aagcataatg aaattattga agaagataca 2340 aacaaagata aacctaatta tcaatttggt ggacacaaca gtgttgattt tgaagaagat 2400 acacttccaa aagtaagtgg tcaaaatgaa ggtcaacaaa cgattgaaga agatacaacg 2460 ccgccaacac cgccaacacc agaggtacca agtgagccgg aaacaccaac accaccaaca 2520 ccagaagtac cgagtgagcc aggcgaacca acgccaccaa aaccggaagt accaagtgag 2580 ccggaaacac cagtaccacc aacaccagag gtaccatctg aacctggtaa accagtacca 2640 cctgctaaag aagaacctaa aaaaccttct aaaccagtgg aacaaggtaa ggtagtaaca 2700 cctgttattg aaatcaatga aaaggttaaa gcagtggcac caactaaaca aaaacaatct 2760 aagaaatctg aactacctga aacaggtgga gaagaatcaa caaacaaagg tatgttgttc 2820 ggcggattat tcagcattct aggtttagta ttattacgca gaaataaaaa gaataacaaa 2880 gcataa 2886 72 1737 PRT S. aureus 72 Ala Thr Gly Ala Ala Ala Thr Thr Thr Ala Ala Gly Thr Cys Ala Thr 1 5 10 15 Thr Gly Ala Thr Thr Ala Cys Ala Ala Cys Ala Ala Cys Ala Thr Thr 20 25 30 Ala Gly Cys Ala Thr Thr Ala Gly Gly Cys Gly Thr Thr Ala Thr Ala 35 40 45 Gly Cys Ala Thr Cys Ala Ala Cys Ala Gly Gly Ala Gly Cys Ala Ala 50 55 60 Ala Cys Thr Thr Thr Ala Ala Thr Ala Cys Thr Ala Ala Cys Gly Ala 65 70 75 80 Ala Gly Cys Ala Thr Cys Thr Gly Cys Cys Gly Cys Ala Gly Cys Thr 85 90 95 Ala Ala Gly Cys Cys Ala Thr Thr Ala Gly Ala Thr Ala Ala 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Ala Thr Cys Thr Gly Gly Thr Ala Ala Ala Gly Ala 450 455 460 Ala Gly Ala Gly Ala Ala Thr Ala Cys Thr Ala Thr Ala Gly Ala Gly 465 470 475 480 Cys Ala Ala Cys Cys Thr Ala Ala Thr Ala Ala Ala Gly Thr Ala Ala 485 490 495 Ala Ala Gly Ala Ala Gly Ala Thr Thr Cys Ala Ala Cys Ala Ala Cys 500 505 510 Ala Ala Gly Thr Cys Ala Gly Cys Cys Gly Thr Cys Thr Gly Gly Cys 515 520 525 Thr Ala Thr Ala Cys Ala Ala Ala Thr Ala Thr Ala Gly Ala Thr Gly 530 535 540 Ala Ala Ala Ala Ala Ala Thr Thr Thr Cys Ala Ala Ala Thr Cys Ala 545 550 555 560 Ala Gly Ala Thr Gly Ala Gly Thr Thr Ala Thr Thr Ala Ala Ala Thr 565 570 575 Thr Thr Ala Cys Cys Ala Ala Thr Ala Ala Ala Thr Gly Ala Ala Thr 580 585 590 Ala Thr Gly Ala Ala Ala Ala Thr Ala Ala Gly Gly Cys Thr Ala Gly 595 600 605 Ala Cys Cys Ala Thr Thr Ala Thr Cys Thr Ala Cys Ala Ala Cys Ala 610 615 620 Thr Cys Thr Gly Cys Cys Cys Ala Ala Cys Cys Ala Thr Cys Gly Ala 625 630 635 640 Thr Thr Ala Ala Ala Cys Gly Thr Gly Thr Ala Ala Cys Cys Gly Thr 645 650 655 Ala Ala Ala Thr Cys Ala Ala Thr Thr Ala Gly Cys Gly Gly Cys Gly 660 665 670 Gly Ala Ala Cys Ala Ala Gly Gly Thr Thr Cys Gly Ala Ala Thr Gly 675 680 685 Thr Thr Ala Ala Thr Cys Ala Thr Thr Thr Ala Ala Thr Thr Ala Ala 690 695 700 Ala Gly Thr Thr Ala Cys Thr Gly Ala Thr Cys Ala Ala Ala Gly Thr 705 710 715 720 Ala Thr Thr Ala Cys Thr Gly Ala Ala Gly Gly Ala Thr Ala Thr Gly 725 730 735 Ala Thr Gly Ala Thr Ala Gly Thr Gly Ala Ala Gly Gly Thr Gly Thr 740 745 750 Thr Ala Thr Thr Ala Ala Ala Gly Cys Ala Cys Ala Thr Gly Ala Thr 755 760 765 Gly Cys Thr Gly Ala Ala Ala Ala Cys Thr Thr Ala Ala Thr Cys Thr 770 775 780 Ala Thr Gly Ala Thr Gly Thr Ala Ala Cys Thr Thr Thr Thr Gly Ala 785 790 795 800 Ala Gly Thr Ala Gly Ala Thr Gly Ala Thr Ala Ala Gly Gly Thr Gly 805 810 815 Ala Ala Ala Thr Cys Thr Gly Gly Thr Gly Ala Thr Ala Cys Gly Ala 820 825 830 Thr Gly Ala Cys Ala Gly Thr Gly Gly Ala Thr Ala Thr Ala Gly Ala 835 840 845 Thr Ala Ala Gly Ala Ala Thr Ala Cys Ala Gly Thr Thr Cys Cys Ala 850 855 860 Thr Cys Ala Gly Ala Thr Thr Thr Ala Ala Cys Cys Gly Ala Thr Ala 865 870 875 880 Gly Cys Thr Thr Thr Ala Cys Ala Ala Thr Ala Cys Cys Ala Ala Ala 885 890 895 Ala Ala Thr Ala Ala Ala Ala Gly Ala Thr Ala Ala Thr Thr Cys Thr 900 905 910 Gly Gly Ala Gly Ala Ala Ala Thr Cys Ala Thr Cys Gly Cys Thr Ala 915 920 925 Cys Ala Gly Gly Thr Ala Cys Thr Thr Ala Thr Gly Ala Thr Ala Ala 930 935 940 Cys Ala Ala Ala Ala Ala Thr Ala Ala Ala Cys Ala Ala Ala Thr Cys 945 950 955 960 Ala Cys Cys Thr Ala Thr Ala Cys Thr Thr Thr Thr Ala Cys Ala Gly 965 970 975 Ala Thr Thr Ala Thr Gly Thr Ala Gly Ala Thr Ala Ala Gly Thr Ala 980 985 990 Thr Gly Ala Ala Ala Ala Thr Ala Thr Thr Ala Ala Ala Gly Cys Ala 995 1000 1005 Cys Ala Cys Cys Thr Thr Ala Ala Ala Thr Thr Ala Ala Cys Gly Thr 1010 1015 1020 Cys Ala Thr Ala Cys Ala Thr Thr Gly Ala Thr Ala Ala Ala Thr Cys 1025 1030 1035 1040 Ala Ala Ala Gly Gly Thr Thr Cys Cys Ala Ala Ala Thr Ala Ala Thr 1045 1050 1055 Ala Ala Thr Ala Cys Cys Ala Ala Gly Thr Thr Ala Gly Ala Thr Gly 1060 1065 1070 Thr Ala Gly Ala Ala Thr Ala Thr Ala Ala Ala Ala Cys Gly Gly Cys 1075 1080 1085 Cys Cys Thr Thr Thr Cys Ala Thr Cys Ala Gly Thr Ala Ala Ala Thr 1090 1095 1100 Ala Ala Ala Ala Cys Ala Ala Thr Thr Ala Cys Gly Gly Thr Thr Gly 1105 1110 1115 1120 Ala Ala Thr Ala Thr Cys Ala Ala Ala Gly Ala Cys Cys Thr Ala Ala 1125 1130 1135 Cys Gly Ala Ala Ala Ala Thr Cys Gly Gly Ala Cys Thr Gly Cys Thr 1140 1145 1150 Ala Ala Cys Cys Thr Thr Cys Ala Ala Ala Gly Thr Ala Thr Gly Thr 1155 1160 1165 Thr Thr Ala Cys Ala Ala Ala Cys Ala Thr Ala Gly Ala Thr Ala Cys 1170 1175 1180 Gly Ala Ala Ala Ala Ala Thr Cys Ala Thr Ala Cys Ala Gly Thr Thr 1185 1190 1195 1200 Gly Ala Gly Cys Ala Ala Ala Cys Gly Ala Thr Thr Thr Ala Thr Ala 1205 1210 1215 Thr Thr Ala Ala Cys Cys Cys Thr Cys Thr Thr Cys Gly Thr Thr Ala 1220 1225 1230 Thr Thr Cys Ala Gly Cys Cys Ala Ala Gly Gly Ala Ala Ala Cys Ala 1235 1240 1245 Ala Ala Thr Gly Thr Ala Ala Ala Thr Ala Thr Thr Thr Cys Ala Gly 1250 1255 1260 Gly Gly Ala Ala Thr Gly Gly Thr Gly Ala Thr Gly Ala Ala Gly Gly 1265 1270 1275 1280 Thr Thr Cys Ala Ala Cys Ala Ala Thr Thr Ala Thr Ala Gly Ala Cys 1285 1290 1295 Gly Ala Thr Ala Gly Cys Ala Cys Ala Ala Thr Ala Ala Thr Thr Ala 1300 1305 1310 Ala Ala Gly Thr Thr Thr Ala Thr Ala Ala Gly Gly Thr Thr Gly Gly 1315 1320 1325 Ala Gly Ala Thr Ala Ala Thr Cys Ala Ala Ala Ala Thr Thr Thr Ala 1330 1335 1340 Cys Cys Ala Gly Ala Thr Ala Gly Thr Ala Ala Cys Ala Gly Ala Ala 1345 1350 1355 1360 Thr Thr Thr Ala Thr Gly Ala Thr Thr Ala Cys Ala Gly Thr Gly Ala 1365 1370 1375 Ala Thr Ala Thr Gly Ala Ala Gly Ala Thr Gly Thr Cys Ala Cys Ala 1380 1385 1390 Ala Ala Thr Gly Ala Thr Gly Ala Thr Thr Ala Thr Gly Cys Cys Cys 1395 1400 1405 Ala Ala Thr Thr Ala Gly Gly Ala Ala Ala Thr Ala Ala Thr Ala Ala 1410 1415 1420 Thr Gly Ala Thr Gly Thr Gly Ala Ala Thr Ala Thr Thr Ala Ala Thr 1425 1430 1435 1440 Thr Thr Thr Gly Gly Thr Ala Ala Thr Ala Thr Ala Gly Ala Thr Thr 1445 1450 1455 Cys Ala Cys Cys Ala Thr Ala Thr Ala Thr Thr Ala Thr Thr Ala Ala 1460 1465 1470 Ala Gly Thr Thr Ala Thr Thr Ala Gly Thr Ala Ala Ala Thr Ala Thr 1475 1480 1485 Gly Ala Cys Cys Cys Thr Ala Ala Thr Ala Ala Gly Gly Ala Thr Gly 1490 1495 1500 Ala Thr Thr Ala Cys Ala Cys Gly Ala Cys Thr Ala Thr Ala Cys Ala 1505 1510 1515 1520 Gly Cys Ala Ala Ala Cys Thr Gly Thr Gly Ala Cys Ala Ala Thr Gly 1525 1530 1535 Cys Ala Gly Ala Cys Gly Ala Cys Thr Ala Thr Ala Ala Ala Thr Gly 1540 1545 1550 Ala Gly Thr Ala Thr Ala Cys Thr Gly Gly Thr Gly Ala Gly Thr Thr 1555 1560 1565 Thr Ala Gly Ala Ala Cys Ala Gly Cys Ala Thr Cys Cys Thr Ala Thr 1570 1575 1580 Gly Ala Thr Ala Ala Thr Ala Cys Ala Ala Thr Thr Gly Cys Thr Thr 1585 1590 1595 1600 Thr Cys Thr Cys Thr Ala Cys Ala Ala Gly Thr Thr Cys Ala Gly Gly 1605 1610 1615 Thr Cys Ala Ala Gly Gly Ala Cys Ala Ala Gly Gly Thr Gly Ala Cys 1620 1625 1630 Thr Thr Gly Cys Cys Thr Cys Cys Thr Gly Ala Ala Ala Ala Ala Ala 1635 1640 1645 Cys Thr Thr Ala Thr Ala Ala Ala Ala Thr Cys Gly Gly Ala Gly Ala 1650 1655 1660 Thr Thr Ala Cys Gly Thr Ala Thr Gly Gly Gly Ala Ala Gly Ala Thr 1665 1670 1675 1680 Gly Thr Ala Gly Ala Thr Ala Ala Ala Gly Ala Thr Gly Gly Thr Ala 1685 1690 1695 Thr Thr Cys Ala Ala Ala Ala Thr Ala Cys Ala Ala Ala Thr Gly Ala 1700 1705 1710 Thr Ala Ala Thr Gly Ala Ala Ala Ala Ala Cys Cys Gly Cys Thr Thr 1715 1720 1725 Ala Gly Thr Ala Ala Thr Gly Thr Ala Thr Thr Gly Gly Thr Ala Ala 1730 1735 1740 Cys Thr Thr Thr Gly Ala Cys Gly Thr Ala Thr Cys Cys Thr Gly Ala 1745 1750 1755 1760 Thr Gly Gly Ala Ala Cys Thr Thr Cys Ala Ala Ala Ala Thr Cys Ala 1765 1770 1775 Gly Thr Cys Ala Gly Ala Ala Cys Ala Gly Ala Thr Gly Ala Ala Gly 1780 1785 1790 Ala Thr Gly Gly Gly Ala Ala Ala Thr Ala Thr Cys Ala Ala Thr Thr 1795 1800 1805 Thr Gly Ala Thr Gly Gly Ala Thr Thr Gly Ala Ala Ala Ala Ala Cys 1810 1815 1820 Gly Gly Ala Thr Thr Gly Ala Cys Thr Thr Ala Thr Ala Ala Ala Ala 1825 1830 1835 1840 Thr Thr Ala Cys Ala Thr Thr Cys Gly Ala Ala Ala Cys Ala Cys Cys 1845 1850

1855 Thr Gly Ala Ala Gly Gly Ala Thr Ala Thr Ala Cys Gly Cys Cys Gly 1860 1865 1870 Ala Cys Gly Cys Thr Thr Ala Ala Ala Cys Ala Thr Thr Cys Ala Gly 1875 1880 1885 Gly Ala Ala Cys Ala Ala Ala Thr Cys Cys Thr Gly Cys Ala Cys Thr 1890 1895 1900 Ala Gly Ala Cys Thr Cys Ala Gly Ala Ala Gly Gly Thr Ala Ala Thr 1905 1910 1915 1920 Thr Cys Thr Gly Thr Ala Thr Gly Gly Gly Thr Ala Ala Cys Thr Ala 1925 1930 1935 Thr Thr Ala Ala Thr Gly Gly Ala Cys Ala Ala Gly Ala Cys Gly Ala 1940 1945 1950 Thr Ala Thr Gly Ala Cys Gly Ala Thr Thr Gly Ala Thr Ala Gly Thr 1955 1960 1965 Gly Gly Ala Thr Thr Thr Thr Ala Thr Cys Ala Ala Ala Cys Ala Cys 1970 1975 1980 Cys Thr Ala Ala Ala Thr Ala Cys Ala Gly Cys Thr Thr Ala Gly Gly 1985 1990 1995 2000 Gly Ala Ala Cys Thr Ala Thr Gly Thr Ala Thr Gly Gly Thr Ala Thr 2005 2010 2015 Gly Ala Cys Ala Cys Thr Ala Ala Thr Ala Ala Ala Gly Ala Thr Gly 2020 2025 2030 Gly Thr Ala Thr Thr Cys Ala Ala Gly Gly Thr Gly Ala Thr Gly Ala 2035 2040 2045 Thr Gly Ala Ala Ala Ala Ala Gly Gly Ala Ala Thr Cys Thr Cys Thr 2050 2055 2060 Gly Gly Ala Gly Thr Thr Ala Ala Ala Gly Thr Gly Ala Cys Gly Thr 2065 2070 2075 2080 Thr Ala Ala Ala Ala Gly Ala Thr Gly Ala Ala Ala Ala Cys Gly Gly 2085 2090 2095 Ala Ala Ala Thr Ala Thr Cys Ala Thr Thr Ala Gly Thr Ala Cys Ala 2100 2105 2110 Ala Cys Thr Ala Cys Ala Ala Cys Cys Gly Ala Thr Gly Ala Ala Ala 2115 2120 2125 Ala Thr Gly Gly Ala Ala Ala Gly Thr Ala Thr Cys Ala Ala Thr Thr 2130 2135 2140 Thr Gly Ala Thr Ala Ala Thr Thr Thr Ala Ala Ala Thr Ala Gly Thr 2145 2150 2155 2160 Gly Gly Thr Ala Ala Thr Thr Ala Thr Ala Thr Thr Gly Thr Thr Cys 2165 2170 2175 Ala Thr Thr Thr Thr Gly Ala Thr Ala Ala Ala Cys Cys Thr Thr Cys 2180 2185 2190 Ala Gly Gly Thr Ala Thr Gly Ala Cys Thr Cys Ala Ala Ala Cys Ala 2195 2200 2205 Ala Cys Ala Ala Cys Ala Gly Ala Thr Thr Cys Thr Gly Gly Thr Gly 2210 2215 2220 Ala Thr Gly Ala Thr Gly Ala Cys Gly Ala Ala Cys Ala Gly Gly Ala 2225 2230 2235 2240 Thr Gly Cys Thr Gly Ala Thr Gly Gly Gly Gly Ala Ala Gly Ala Ala 2245 2250 2255 Gly Thr Thr Cys Ala Thr Gly Thr Ala Ala Cys Ala Ala Thr Thr Ala 2260 2265 2270 Cys Thr Gly Ala Thr Cys Ala Thr Gly Ala Thr Gly Ala Cys Thr Thr 2275 2280 2285 Thr Ala Gly Thr Ala Thr Ala Gly Ala Thr Ala Ala Cys Gly Gly Ala 2290 2295 2300 Thr Ala Cys Thr Ala Thr Gly Ala Thr Gly Ala Cys Gly Ala Ala 2305 2310 2315

Claims

1. An immunogenic composition comprising at least two different proteins or immunogenic fragments thereof selected from at least two groups of proteins or immunogenic fragments selected from the following groups: Group a) at least one staphylococcal extracellular component binding protein or immunogenic fragment thereof selected from the group consisting of SdrG, laminin receptor, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrH, Lipase GehD, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, coagulase, and MAP; Group b) at least one staphylococcal transporter protein or immunogenic fragment thereof selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC and Ni ABC transporter; Group c) at least one staphylococcal regulator of virulence, toxin or immunogenic fragment thereof selected from the group consisting of alpha toxin (Hla), alpha toxin H35R mutant and RNA III activating protein (RAP).

2. The immunogenic composition of claim 1 wherein at least one protein or immunogenic fragment is selected from group a).

3. The immunogenic composition of claim 1 wherein at least one protein or immunogenic fragment is selected from group b).

4. The immunogenic composition of claim 1 wherein at least one protein or immunogenic fragment is selected from group c).

5. The immunogenic composition of claim 1 wherein at least one protein or immunogenic fragment is selected from group a), group b) and group c).

6. The immunogenic composition of claim 1 comprising at least one protein or immunogenic fragment from S. aureus.

7. The immunogenic composition of claim 1 comprising at least one protein or immunogenic fragment from S. epidermidis.

8. The immunogenic composition of claim 1 further comprising a PIA polysaccharide or oligosaccharide.

9. The immunogenic composition of claim 1 further comprising type V and/or type VIII capsular polysaccharide or oligosaccharide from S. aureus.

10. The immunogenic composition of claim 1 further comprising Type 1, and/or Type II and/or Type III capsular polysaccharide or oligosaccharide from S. epidermidis.

11. The immunogenic composition of claim 1 further comprising lipoteichoic acid from a Gram positive bacterium.

12. The immunogenic composition of claim 11 wherein the lipoteichoic acid is extracted from staphylococcal bacterium.

13. The immunogenic composition of claim 8 wherein a staphylococcal capsular polysaccharide is conjugated to a protein carrier.

14. The immunogenic composition of claim 11 wherein the lipoteichoic acid is conjugated to a protein carrier.

15. The immunogenic composition of claim 13 wherein the protein carrier is selected from the group consisting of tetanus toxoid, diphtheria toxoid, CRM197, Haemophilus influenzae protein D, pneumolysin and alpha toxoid.

16. The immunogenic composition of claim 1 which is capable of generating an effective immune response against both S. aureus and S. epidermidis.

17. A vaccine comprising the immunogenic composition of claim 1 and a pharmaceutically acceptable excipient.

18. A method of making a vaccine comprising the steps of mixing antigens to make the immunogenic composition of claim 1 and adding a pharmaceutically acceptable excipient.

19. A method of preventing or treating staphylococcal infection comprising the step of administering the vaccine of claim 17 to a patient in need thereof.

20. (canceled)

21. A method for preparing an immune globulin for use in prevention or treatment of staphylococcal infection comprising the steps of immunizing a recipient with the vaccine of claim 17 and isolating immune globulin from the recipient.

22. A pharmaceutical composition comprising two or more monoclonal antibodies or fragments thereof which are reactive against at least two constituents of the immunogenic composition of claim 1 wherein the at least two constituents are selected from at least 2 groups a), b) and c).

23. A pharmaceutical composition comprising the immune globulin of claim 21 and a pharmaceutically acceptable excipient.

24. A method for treatment or prevention of staphylococcal infection comprising a step of administering to a patient an effective amount of the pharmaceutical composition of claim 22.

25. (canceled)