Streptococcus pneumoniae Antigens and Vaccines

Abstract

The present invention relates to novel vaccines for the prevention or attenuation of infection by Streptococcus pneumoniae. The invention further relates to isolated nucleic acid molecules encoding antigenic polypeptides of Streptococcus pneumoniae. Antigenic polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention additionally relates to diagnostic methods for detecting Streptococcus nucleic acids, polypeptides and antibodies in a biological sample.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a divisional of U.S. application Ser. No. 11/106,649, filed Apr. 15, 2005, which is a divisional of U.S. application Ser. No. 08/961,083, filed Oct. 30, 1997 (now U.S. Pat. No. 7,056,510, issued Jun. 6, 2006), which claims benefit of U.S. Provisional Application No. 60/029,960, filed Oct. 31, 1996; this application is also a divisional of U.S. application Ser. No. 09/765,271, filed Jan. 22, 2001, which is a continuation of U.S. application Ser. No. 09/536,784, filed Mar. 28, 2000 (now U.S. Pat. No. 6,573,082, issued Jun. 3, 2003), which is a continuation of U.S. application Ser. No. 08/961,083, filed Oct. 30, 1997, which claims benefit of U.S. Provisional Application No. 60/029,960, filed Oct. 31, 1996; U.S. application Ser. No. 09/765,271 is also a continuation of U.S. application Ser. No. 08/961,083, filed Oct. 30, 1997, which claims benefit of U.S. Provisional Application No. 60/029,960, filed Oct. 31, 1996.

STATEMENT UNDER 37 C.F.R. .sctn.1.77(b)(5)

[0002] This application refers to a "Sequence Listing" listed below, which is provided as a text document. The document is entitled "PB340P2C3D2_ST25.txt" (531,801 bytes, created on Apr. 12, 2010), which is incorporated by reference in its entirety.

FIELD OF THE INVENTION

[0003] The present invention relates to novel Streptococcus pneumoniae antigens for the detection of Streptococcus and for the prevention or attenuation of disease caused by Streptococcus. The invention further relates to isolated nucleic acid molecules encoding antigenic polypeptides of S. pneumoniae. Antigenic polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention additionally relates to diagnostic methods for detecting Streptococcus gene expression.

BACKGROUND OF THE INVENTION

[0004] Streptococcus pneumoniae has been one of the most extensively studied microorganisms since its first isolation in 1881. It was the object of many investigations that led to important scientific discoveries. In 1928, Griffith observed that when heat-killed encapsulated pneumococci and live strains constitutively lacking any capsule were concomitantly injected into mice, the nonencapsulated could be converted into encapsulated pneumococci with the same capsular type as the heat-killed strain. Years later, the nature of this "transforming principle," or carrier of genetic information, was shown to be DNA. (Avery, O. T., et al., J. Exp. Med., 79:137-157 (1944)).

[0005] In spite of the vast number of publications on S. pneumoniae many questions about its virulence are still unanswered, and this pathogen remains a major causative agent of serious human disease, especially community-acquired pneumonia. (Johnston, R. B., et al., Rev. Infect. Dis. 13(Suppl. 6):S509-517 (1991)). In addition, in developing countries, the pneumococcus is responsible for the death of a large number of children under the age of 5 years from pneumococcal pneumonia. The incidence of pneumococcal disease is highest in infants under 2 years of age and in people over 60 years of age. Pneumococci are the second most frequent cause (after Haemophilus influenzae type b) of bacterial meningitis and otitis media in children. With the recent introduction of conjugate vaccines for H. influenzae type b, pneumococcal meningitis is likely to become increasingly prominent. S. pneumoniae is the most important etiologic agent of community-acquired pneumonia in adults and is the second most common cause of bacterial meningitis behind Neisseria meningitidis.

[0006] The antibiotic generally prescribed to treat S. pneumoniae is benzylpenicillin, although resistance to this and to other antibiotics is found occasionally. Pneumococcal resistance to penicillin results from mutations in its penicillin-binding proteins. In uncomplicated pneumococcal pneumonia caused by a sensitive strain, treatment with penicillin is usually successful unless started too late. Erythromycin or clindamycin can be used to treat pneumonia in patients hypersensitive to penicillin, but resistant strains to these drugs exist. Broad spectrum antibiotics (e.g., the tetracyclines) may also be effective, although tetracycline-resistant strains are not rare. In spite of the availability of antibiotics, the mortality of pneumococcal bacteremia in the last four decades has remained stable between 25 and 29%. (Gillespie, S. H., et al., J. Med. Microbiol. 28:237-248 (1989).

[0007] S. pneumoniae is carried in the upper respiratory tract by many healthy individuals. It has been suggested that attachment of pneumococci is mediated by a disaccharide receptor on fibronectin, present on human pharyngeal epithelial cells. (Anderson, B. J., et al., J. Immunol. 142:2464-2468 (1989). The mechanisms by which pneumococci translocate from the nasopharynx to the lung, thereby causing pneumonia, or migrate to the blood, giving rise to bacteremia or septicemia, are poorly understood. (Johnston, R. B., et al., Rev. Infect. Dis. 13(Suppl. 6):S509-517 (1991).

[0008] Various proteins have been suggested to be involved in the pathogenicity of S. pneumoniae, however, only a few of them have actually been confirmed as virulence factors. Pneumococci produce an IgA1 protease that might interfere with host defense at mucosal surfaces. (Kornfield, S. J., et al., Rev. Inf. Dis. 3:521-534 (1981). S. pneumoniae also produces neuraminidase, an enzyme that may facilitate attachment to epithelial cells by cleaving sialic acid from the host glycolipids and gangliosides. Partially purified neuraminidase was observed to induce meningitis-like symptoms in mice; however, the reliability of this finding has been questioned because the neuraminidase preparations used were probably contaminated with cell wall products. Other pneumococcal proteins besides neuraminidase are involved in the adhesion of pneumococci to epithelial and endothelial cells. These pneumococcal proteins have as yet not been identified. Recently, Cundell et al., reported that peptide permeases can modulate pneumococcal adherence to epithelial and endothelial cells. It was, however, unclear whether these permeases function directly as adhesions or whether they enhance adherence by modulating the expression of pneumococcal adhesions. (DeVelasco, E. A., et al., Micro. Rev. 59:591-603 (1995). A better understanding of the virulence factors determining its pathogenicity will need to be developed to cope with the devastating effects of pneumococcal disease in humans.

[0009] Ironically, despite the prominent role of S. pneumoniae in the discovery of DNA, little is known about the molecular genetics of the organism. The S. pneumoniae genome consists of one circular, covalently closed, double-stranded DNA and a collection of so-called variable accessory elements, such as prophages, plasmids, transposons and the like. Most physical characteristics and almost all of the genes of S. pneumoniae are unknown. Among the few that have been identified, most have not been physically mapped or characterized in detail. Only a few genes of this organism have been sequenced. (See, for instance current versions of GENBANK and other nucleic acid databases, and references that relate to the genome of S. pneumoniae such as those set out elsewhere herein.) Identification of in vivo-expressed, and broadly protective, antigens of S. pneumoniae has remained elusive.

SUMMARY OF THE INVENTION

[0010] The present invention provides isolated nucleic acid molecules comprising polynucleotides encoding the S. pneumoniae polypeptides described in Table 1 and having the amino acid sequences shown as SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, and so on through SEQ ID NO:226. Thus, one aspect of the invention provides isolated nucleic acid molecules comprising polynucleotides having a nucleotide sequence selected from the group consisting of: (a) a nucleotide sequence encoding any of the amino acid sequences of the polypeptides shown in Table 1; and (b) a nucleotide sequence complementary to any of the nucleotide sequences in (a).

[0011] Further embodiments of the invention include isolated nucleic acid molecules that comprise a polynucleotide having a nucleotide sequence at least 90% identical, and more preferably at least 95%, 96%, 97%, 98% or 99% identical, to any of the nucleotide sequences in (a) or (b) above, or a polynucleotide which hybridizes under stringent hybridization conditions to a polynucleotide in (a) or (b) above. This polynucleotide which hybridizes does not hybridize under stringent hybridization conditions to a polynucleotide having a nucleotide sequence consisting of only A residues or of only T residues. Additional nucleic acid embodiments of the invention relate to isolated nucleic acid molecules comprising polynucleotides which encode the amino acid sequences of epitope-bearing portions of an S. pneumoniae polypeptide having an amino acid sequence in (a) above.

[0012] The present invention also relates to recombinant vectors, which include the isolated nucleic acid molecules of the present invention, and to host cells containing the recombinant vectors, as well as to methods of making such vectors and host cells and for using these vectors for the production of S. pneumoniae polypeptides or peptides by recombinant techniques.

[0013] The invention further provides isolated S. pneumoniae polypeptides having an amino acid sequence selected from the group consisting of an amino acid sequence of any of the polypeptides described in Table 1.

[0014] The polypeptides of the present invention also include polypeptides having an amino acid sequence with at least 70% similarity, and more preferably at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% similarity to those described in Table 1, as well as polypeptides having an amino acid sequence at least 70% identical, more preferably at least 75% identical, and still more preferably 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to those above; as well as isolated nucleic acid molecules encoding such polypeptides.

[0015] The present invention further provides a vaccine, preferably a multi-component vaccine comprising one or more of the S. pneumoniae polynucleotides or polypeptides described in Table 1, or fragments thereof, together with a pharmaceutically acceptable diluent, carrier, or excipient, wherein the S. pneumoniae polypeptide(s) are present in an amount effective to elicit an immune response to members of the Streptococcus genus in an animal. The S. pneumoniae polypeptides of the present invention may further be combined with one or more immunogens of one or more other streptococcal or non-streptococcal organisms to produce a multi-component vaccine intended to elicit an immunological response against members of the Streptococcus genus and, optionally, one or more non-streptococcal organisms.

[0016] The vaccines of the present invention can be administered in a DNA form, e.g., "naked" DNA, wherein the DNA encodes one or more streptococcal polypeptides and, optionally, one or more polypeptides of a non-streptococcal organism. The DNA encoding one or more polypeptides may be constructed such that these polypeptides are expressed fusion proteins.

[0017] The vaccines of the present invention may also be administered as a component of a genetically engineered organism. Thus, a genetically engineered organism which expresses one or more S. pneumoniae polypeptides may be administered to an animal. For example, such a genetically engineered organism may contain one or more S. pneumoniae polypeptides of the present invention intracellularly, on its cell surface, or in its periplasmic space. Further, such a genetically engineered organism may secrete one or more S. pneumoniae polypeptides.

[0018] The vaccines of the present invention may be co-administered to an animal with an immune system modulator (e.g., CD86 and GM-CSF).

[0019] The invention also provides a method of inducing an immunological response in an animal to one or more members of the Streptococcus genus, preferably one or more isolates of the S. pneumoniae genus, comprising administering to the animal a vaccine as described above.

[0020] The invention further provides a method of inducing a protective immune response in an animal, sufficient to prevent or attenuate an infection by members of the Streptococcus genus, preferably at least S. pneumoniae, comprising administering to the animal a composition comprising one or more of the polynucleotides or polypeptides described in Table 1, or fragments thereof. Further, these polypeptides, or fragments thereof, may be conjugated to another immunogen and/or administered in admixture with an adjuvant.

[0021] The invention further relates to antibodies elicited in an animal by the administration of one or more S. pneumoniae polypeptides of the present invention and to methods for producing such antibodies.

[0022] The invention also provides diagnostic methods for detecting the expression of genes of members of the Streptococcus genus in an animal. One such method involves assaying for the expression of a gene encoding S. pneumoniae peptides in a sample from an animal. This expression may be assayed either directly (e.g., by assaying polypeptide levels using antibodies elicited in response to amino acid sequences described in Table 1) or indirectly (e.g., by assaying for antibodies having specificity for amino acid sequences described in Table 1). An example of such a method involves the use of the polymerase chain reaction (PCR) to amplify and detect Streptococcus nucleic acid sequences.

[0023] The present invention also relates to nucleic acid probes having all or part of a nucleotide sequence described in Table 1 (shown as SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, and so on through SEQ ID NO:225) which are capable of hybridizing under stringent conditions to Streptococcus nucleic acids. The invention further relates to a method of detecting one or more Streptococcus nucleic acids in a biological sample obtained from an animal, said one or more nucleic acids encoding Streptococcus polypeptides, comprising: (a) contacting the sample with one or more of the above-described nucleic acid probes, under conditions such that hybridization occurs, and (b) detecting hybridization of said one or more probes to the Streptococcus nucleic acid present in the biological sample.

[0024] The invention also includes immunoassays, including an immunoassay for detecting Streptococcus, preferably at least isolates of the S. pneumoniae genus, comprising incubation of a sample (which is suspected of being infected with Streptococcus) with a probe antibody directed against an antigen/epitope of S. pneumoniae, to be detected under conditions allowing the formation of an antigen-antibody complex; and detecting the antigen-antibody complex which contains the probe antibody. An immunoassay for the detection of antibodies which are directed against a Streptococcus antigen comprising the incubation of a sample (containing antibodies from a mammal suspected of being infected with Streptococcus) with a probe polypeptide including an epitope of S. pneumoniae, under conditions that allow the formation of antigen-antibody complexes which contain the probe epitope containing antigen.

[0025] Some aspects of the invention pertaining to kits are those for: investigating samples for the presence of polynucleotides derived from Streptococcus which comprise a polynucleotide probe including a nucleotide sequence selected from Table 1 or a fragment thereof of approximately 15 or more nucleotides, in an appropriate container; analyzing the samples for the presence of antibodies directed against a Streptococcus antigen made up of a polypeptide which contains a S. pneumoniae epitope present in the polypeptide, in a suitable container; and analyzing samples for the presence of Streptococcus antigens made up of an anti-S. pneumoniae antibody, in a suitable container.

DETAILED DESCRIPTION

[0026] The present invention relates to recombinant antigenic S. pneumoniae polypeptides and fragments thereof. The invention also relates to methods for using these polypeptides to produce immunological responses and to confer immunological protection to disease caused by members of the genus Streptococcus, at least isolates of the S. pneumoniae genus. The invention further relates to nucleic acid sequences which encode antigenic S. pneumoniae polypeptides and to methods for detecting S. pneumoniae nucleic acids and polypeptides in biological samples. The invention also relates to S. pneumoniae-specific antibodies and methods for detecting such antibodies produced in a host animal.

DEFINITIONS

[0027] The following definitions are provided to clarify the subject matter which the inventors consider to be the present invention.

[0028] As used herein, the phrase "pathogenic agent" means an agent which causes a disease state or affliction in an animal. Included within this definition, for examples, are bacteria, protozoans, fungi, viruses and metazoan parasites which either produce a disease state or render an animal infected with such an organism susceptible to a disease state (e.g., a secondary infection). Further included are species and strains of the genus Streptococcus which produce disease states in animals.

[0029] As used herein, the term "organism" means any living biological system, including viruses, regardless of whether it is a pathogenic agent.

[0030] As used herein, the term "Streptococcus" means any species or strain of bacteria which is members of the genus Streptococcus. Such species and strains are known to those of skill in the art, and include those that are pathogenic and those that are not.

[0031] As used herein, the phrase "one or more S. pneumoniae polypeptides of the present invention" means polypeptides comprising the amino acid sequence of one or more of the S. pneumoniae polypeptides described in Table 1 and disclosed as SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, and so on through SEQ ID NO:226. These polypeptides may be expressed as fusion proteins wherein the S. pneumoniae polypeptides of the present invention are linked to additional amino acid sequences which may be of streptococcal or non-streptococcal origin. This phrase further includes polypeptide comprising fragments of the S. pneumoniae polypeptides of the present invention.

[0032] Additional definitions are provided throughout the specification.

Explanation of Table 1

[0033] Table 1, below, provides information describing 113 open reading frames (ORFs) which encode potentially antigenic polypeptides of S. pneumoniae of the present invention. The table lists the ORF identifier which consists of the letters SP, which denote S. pneumoniae, followed immediately by a three digit numeric code, which arbitrarily number the potentially antigenic polypeptides of S. pneumoniae of the present invention. The table further correlates the ORF identifier with a sequence identification number (SEQ ID NO:). The actual nucleotide or amino acid sequence of each ORF identifier is shown in the Sequence Listing under the corresponding SEQ ID NO.

[0034] Thus, for example, the designation "SP126" refers to both the nucleotide and amino acid sequences of S. pneumoniae polypeptide number 126 of the present invention. Further, "SP126" correlates with the nucleotide sequence shown as SEQ ID NO:223 and with the amino acid sequence shown as SEQ ID NO:224 as is described in Table 1.

[0035] The open reading frame within each "ORF" begins with the second nucleotide shown. Thus, the first codon for each nucleotide sequence shown is bases 2-4, the second 5-7, the third 8-10, and so on.

Explanation of Table 2

[0036] Table 2 lists the antigenic epitopes present in each of the S. pneumoniae polypeptides described in Table 1 as predicted by the inventors. Each S. pneumoniae polypeptide shown in Table 1 has one or more antigenic epitopes described in Table 2. It will be appreciated that depending on the analytical criteria used to predict antigenic determinants, the exact address of the determinant may vary slightly. The exact location of the antigenic determinant may shift by about 1 to 5 residues, more likely 1 to 2 residues, depending on the criteria used. Thus, the first antigenic determinant described in Table 2, "Lys-1 to Ile-10" of SP001, represents a peptide comprising the lysine at position 1 in SEQ ID NO:2 through and including the isoleucine at position 10 in SEQ ID NO:2, but may include more or fewer residues than those 10. It will also be appreciated that, generally speaking, amino acids can be added to either terminus of a peptide or polypeptide containing an antigenic epitope without affecting its activity, whereas removing residues from a peptide or polypeptide containing only the antigenic determinant is much more likely to destroy activity. It will be appreciated that the residues and locations shown described in Table 2 correspond to the amino acid sequences for each ORF shown in Table 1 and in the Sequence Listing.

Explanation of Table 3

[0037] Table 3 shows PCR primers designed by the inventors for the amplification of polynucleotides encoding polypeptides of the present invention according to the method of Example 1. PCR primer design is routine in the art and those shown in Table 3 are provided merely for the convenience of the skilled artisan. It will be appreciated that others can be used with equal success. For each primer, the table lists the corresponding ORF designation from Table 1 followed by either an "A" or a "B". The "A" primers are the 5' primers and the "B" primers 3'. A restriction enzyme site was built into each primer to allow ease of cloning. The restriction enzyme which will recognize and cleave a sequence within each primer is shown in Table 3, as well, under the heading "RE" for restriction enzyme. Finally the sequence identifier is shown in Table 3 for each primer for easy correlation with the Sequence Listing.

Selection of Nucleic Acid Sequences Encoding Antigenic S. Pneumoniae Polypeptides

[0038] The present invention provides a select number of ORFs from those presented in the fragments of the S. pneumoniae genome which may prove useful for the generation of a protective immune response. The sequenced S. pneumoniae genomic DNA was obtained from a sub-cultured isolate of S. pneumoniae Strain 7/87 14.8.91, which has been deposited at the American Type Culture Collection, as a convenience to those of skill in the art. The S. pneumoniae isolate was deposited on Oct. 10, 1996 at the ATCC.TM., 10801 University Boulevard, Manassas, Va. 20110-2209 (present address), and given accession number 55840. A genomic library constructed from DNA isolated from the S. pneumoniae isolate was also deposited at the ATCC.TM. on Oct. 11, 1996 and given ATCC.TM. Deposit No. 97755. A more complete listing of the sequence obtained from the S. pneumoniae genome may be found in co-pending U.S. Provisional Application Ser. No. 60/029,960, filed Oct. 31, 1996, incorporated herein by reference in its entirety. Some ORFs contained in the subset of fragments of the S. pneumoniae genome disclosed herein were derived through the use of a number of screening criteria detailed below.

[0039] The selected ORFs do not consist of complete ORFs. Although a polypeptide representing a complete ORF may be the closest approximation of a protein native to an organism, it is not always preferred to express a complete ORF in a heterologous system. It may be challenging to express and purify a highly hydrophobic protein by common laboratory methods. Thus, the polypeptide vaccine candidates described herein may have been modified slightly to simplify the production of recombinant protein. For example, nucleotide sequences which encode highly hydrophobic domains, such as those found at the amino terminal signal sequence, have been excluded from some constructs used for in vitro expression of the polypeptides. Furthermore, any highly hydrophobic amino acid sequences occurring at the carboxy terminus have also been excluded from the recombinant expression constructs. Thus, in one embodiment, a polypeptide which represents a truncated or modified ORF may be used as an antigen.

[0040] While numerous methods are known in the art for selecting potentially immunogenic polypeptides, many of the ORFs disclosed herein were selected on the basis of screening all theoretical S. pneumoniae ORFs for several aspects of potential immunogenicity. One set of selection criteria are as follows:

[0041] 1. Type I signal sequence: An amino terminal type I signal sequence generally directs a nascent protein across the plasma and outer membranes to the exterior of the bacterial cell. Experimental evidence obtained from studies with Escherichia coli suggests that the typical type I signal sequence consists of the following biochemical and physical attributes (Izard, J. W. and Kendall, D. A. Mol. Microbiol. 13:765-773 (1994)). The length of the type I signal sequence is approximately 15 to 25 primarily hydrophobic amino acid residues with a net positive charge in the extreme amino terminus. In addition, the central region of the signal sequence adopts an alpha-helical conformation in a hydrophobic environment. Finally, the region surrounding the actual site of cleavage is ideally six residues long, with small side-chain amino acids in the -1 and -3 positions.

[0042] 2. Type IV signal sequence: The type IV signal sequence is an example of the several types of functional signal sequences which exist in addition to the type I signal sequence detailed above. Although functionally related, the type IV signal sequence possesses a unique set of biochemical and physical attributes (Strom, M. S, and Lory, S., J. Bacteriol. 174:7345-7351 (1992)). These are typically six to eight amino acids with a net basic charge followed by an additional sixteen to thirty primarily hydrophobic residues. The cleavage site of a type IV signal sequence is typically after the initial six to eight amino acids at the extreme amino terminus. In addition, type IV signal sequences generally contain a phenylalanine residue at the +1 site relative to the cleavage site.

[0043] 3. Lipoprotein: Studies of the cleavage sites of twenty-six bacterial lipoprotein precursors has allowed the definition of a consensus amino acid sequence for lipoprotein cleavage. Nearly three-fourths of the bacterial lipoprotein precursors examined contained the sequence L-(A,S)-(G,A)-C (SEQ ID NO:453) at positions -3 to +1, relative to the point of cleavage (Hayashi, S, and Wu, H. C., J. Bioenerg. Biomembr. 22:451-471 (1990)).

[0044] 4. LPXTG motif: It has been experimentally determined that most anchored proteins found on the surface of gram-positive bacteria possess a highly conserved carboxy terminal sequence. More than fifty such proteins from organisms such as S. pyogenes, S. mutans, E. faecalis, S. pneumoniae, and others, have been identified based on their extracellular location and carboxy terminal amino acid sequence (Fischetti, V. A., ASM News 62:405-410 (1996)). The conserved region consists of six charged amino acids at the extreme carboxy terminus coupled to 15-20 hydrophobic amino acids presumed to function as a transmembrane domain. Immediately adjacent to the transmembrane domain is a six amino acid sequence conserved in nearly all proteins examined. The amino acid sequence of this region is L-P-X-T-G-X (SEQ ID NO:454), where X is any amino acid.

[0045] An algorithm for selecting antigenic and immunogenic S. pneumoniae polypeptides including the foregoing criteria was developed. Use of the algorithm by the inventors to select immunologically useful S. pneumoniae polypeptides resulted in the selection of a number of the disclosed ORFs. Polypeptides comprising the polypeptides identified in this group may be produced by techniques standard in the art and as further described herein.

Nucleic Acid Molecules

[0046] The present invention provides isolated nucleic acid molecules comprising polynucleotides encoding the S. pneumoniae polypeptides having the amino acid sequences described in Table 1 and shown as SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, and so on through SEQ ID NO:226, which were determined by sequencing the genome of S. pneumoniae and selected as putative immunogens.

[0047] Unless otherwise indicated, all nucleotide sequences determined by sequencing a DNA molecule herein were determined using an automated DNA sequencer (such as the Model 373 from Applied Biosystems, Inc.), and all amino acid sequences of polypeptides encoded by DNA molecules determined herein were predicted by translation of DNA sequences determined as above. Therefore, as is known in the art for any DNA sequence determined by this automated approach, any nucleotide sequence determined herein may contain some errors. Nucleotide sequences determined by automation are typically at least about 90% identical, more typically at least about 95% to at least about 99.9% identical to the actual nucleotide sequence of the sequenced DNA molecule. The actual sequence can be more precisely determined by other approaches including manual DNA sequencing methods well known in the art. As is also known in the art, a single insertion or deletion in a determined nucleotide sequence compared to the actual sequence will cause a frame shift in translation of the nucleotide sequence such that the predicted amino acid sequence encoded by a determined nucleotide sequence will be completely different from the amino acid sequence actually encoded by the sequenced DNA molecule, beginning at the point of such an insertion or deletion.

[0048] Unless otherwise indicated, each "nucleotide sequence" set forth herein is presented as a sequence of deoxyribonucleotides (abbreviated A, G, C and T). However, by "nucleotide sequence" of a nucleic acid molecule or polynucleotide is intended, for a DNA molecule or polynucleotide, a sequence of deoxyribonucleotides, and for an RNA molecule or polynucleotide, the corresponding sequence of ribonucleotides (A, G, C and U), where each thymidine deoxyribonucleotide (T) in the specified deoxyribonucleotide sequence is replaced by the ribonucleotide uridine (U). For instance, reference to an RNA molecule having a sequence described in Table 1 set forth using deoxyribonucleotide abbreviations is intended to indicate an RNA molecule having a sequence in which each deoxyribonucleotide A, G or C described in Table 1 has been replaced by the corresponding ribonucleotide A, G or C, and each deoxyribonucleotide T has been replaced by a ribonucleotide U.

[0049] Nucleic acid molecules of the present invention may be in the form of RNA, such as mRNA, or in the form of DNA, including, for instance, cDNA and genomic DNA obtained by cloning or produced synthetically. The DNA may be double-stranded or single-stranded. Single-stranded DNA or RNA may be the coding strand, also known as the sense strand, or it may be the non-coding strand, also referred to as the anti-sense strand.

[0050] By "isolated" nucleic acid molecule(s) is intended a nucleic acid molecule, DNA or RNA, which has been removed from its native environment. For example, recombinant DNA molecules contained in a vector are considered isolated for the purposes of the present invention. Further examples of isolated DNA molecules include recombinant DNA molecules maintained in heterologous host cells or purified (partially or substantially) DNA molecules in solution. Isolated RNA molecules include in vivo or in vitro RNA transcripts of the DNA molecules of the present invention. Isolated nucleic acid molecules according to the present invention further include such molecules produced synthetically.

[0051] Isolated nucleic acid molecules of the present invention include DNA molecules comprising a nucleotide sequence described in Table 1 and shown as SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, and so on through SEQ ID NO:225; DNA molecules comprising the coding sequences for the polypeptides described in Table 1 and shown as SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, and so on through SEQ ID NO:226; and DNA molecules which comprise sequences substantially different from those described above but which, due to the degeneracy of the genetic code, still encode the S. pneumoniae polypeptides described in Table 1. Of course, the genetic code is well known in the art. Thus, it would be routine for one skilled in the art to generate such degenerate variants.

[0052] The invention also provides nucleic acid molecules having sequences complementary to any one of those described in Table 1. Such isolated molecules, particularly DNA molecules, are useful as probes for detecting expression of Streptococcal genes, for instance, by Northern blot analysis or the polymerase chain reaction (PCR).

[0053] The present invention is further directed to fragments of the isolated nucleic acid molecules described herein. By a fragment of an isolated nucleic acid molecule having a nucleotide sequence described in Table 1, is intended fragments at least about 15 nt, and more preferably at least about 17 nt, still more preferably at least about 20 nt, and even more preferably, at least about 25 nt in length which are useful as diagnostic probes and primers as discussed herein. Of course, larger fragments 50-100 nt in length are also useful according to the present invention as are fragments corresponding to most, if not all, of a nucleotide sequence described in Table 1. By a fragment at least 20 nt in length, for example, is intended fragments which include 20 or more contiguous bases of a nucleotide sequence as described in Table 1. Since the nucleotide sequences identified in Table 1 are provided as SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, and so on through SEQ ID NO:225, generating such DNA fragments would be routine to the skilled artisan. For example, such fragments could be generated synthetically.

[0054] Preferred nucleic acid fragments of the present invention also include nucleic acid molecules comprising nucleotide sequences encoding epitope-bearing portions of the S. pneumoniae polypeptides identified in Table 1. Such nucleic acid fragments of the present invention include, for example, nucleotide sequences encoding polypeptide fragments comprising from about the amino terminal residue to about the carboxy terminal residue of each fragment shown in Table 2. The above referred to polypeptide fragments are antigenic regions of the S. pneumoniae polypeptides identified in Table 1.

[0055] In another aspect, the invention provides isolated nucleic acid molecules comprising polynucleotides which hybridize under stringent hybridization conditions to a portion of a polynucleotide in a nucleic acid molecule of the invention described above, for instance, a nucleic acid sequence identified in Table 1. By "stringent hybridization conditions" is intended overnight incubation at 42.degree. C. in a solution comprising: 50% formamide, 5.times.SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5.times.Denhardt's solution, 10% dextran sulfate, and 20 g/ml denatured, sheared salmon sperm DNA, followed by washing the filters in 0.1.times.SSC at about 65.degree. C.

[0056] By polynucleotides which hybridize to a "portion" of a polynucleotide is intended polynucleotides (either DNA or RNA) which hybridize to at least about 15 nucleotides (nt), and more preferably at least about 17 nt, still more preferably at least about 20 nt, and even more preferably about 25-70 nt of the reference polynucleotide. These are useful as diagnostic probes and primers as discussed above and in more detail below.

[0057] Of course, polynucleotides hybridizing to a larger portion of the reference polynucleotide, for instance, a portion 50-100 nt in length, or even to the entire length of the reference polynucleotide, are also useful as probes according to the present invention, as are polynucleotides corresponding to most, if not all, of a nucleotide sequence as identified in Table 1. By a portion of a polynucleotide of "at least 20 nt in length," for example, is intended 20 or more contiguous nucleotides from the nucleotide sequence of the reference polynucleotide (e.g., a nucleotide sequences as described in Table 1). As noted above, such portions are useful diagnostically either as probes according to conventional DNA hybridization techniques or as primers for amplification of a target sequence by PCR, as described in the literature (for instance, in Molecular Cloning, A Laboratory Manual, 2nd. edition, Sambrook, J., Fritsch, E. F. and Maniatis, T., eds., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989), the entire disclosure of which is hereby incorporated herein by reference).

[0058] Since nucleic acid sequences encoding the S. pneumoniae polypeptides of the present invention are identified in Table 1 and provided as SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, and so on through SEQ ID NO:225, generating polynucleotides which hybridize to portions of these sequences would be routine to the skilled artisan. For example, the hybridizing polynucleotides of the present invention could be generated synthetically according to known techniques.

[0059] As indicated, nucleic acid molecules of the present invention which encode S. pneumoniae polypeptides of the present invention may include, but are not limited to those encoding the amino acid sequences of the polypeptides by themselves; and additional coding sequences which code for additional amino acids, such as those which provide additional functionalities. Thus, the sequences encoding these polypeptides may be fused to a marker sequence, such as a sequence encoding a peptide which facilitates purification of the fused polypeptide. In certain preferred embodiments of this aspect of the invention, the marker amino acid sequence is a hexa-histidine peptide, such as the tag provided in a pQE vector (Qiagen, Inc.), among others, many of which are commercially available. As described by Gentz and colleagues (Proc. Natl. Acad. Sci. USA 86:821-824 (1989)), for instance, hexa-histidine provides for convenient purification of the resulting fusion protein.

[0060] Thus, the present invention also includes genetic fusions wherein the S. pneumoniae nucleic acid sequences coding sequences identified in Table 1 are linked to additional nucleic acid sequences to produce fusion proteins. These fusion proteins may include epitopes of streptococcal or non-streptococcal origin designed to produce proteins having enhanced immunogenicity. Further, the fusion proteins of the present invention may contain antigenic determinants known to provide helper T-cell stimulation, peptides encoding sites for post-translational modifications which enhance immunogenicity (e.g., acylation), peptides which facilitate purification (e.g., histidine "tag"), or amino acid sequences which target the fusion protein to a desired location (e.g., a heterologous leader sequence).

[0061] In all cases of bacterial expression, an N-terminal methionine residues is added. In many cases, however, the N-terminal methionine residues is cleaved off post-translationally. Thus, the invention includes polypeptides shown in Table 1 with, and without an N-terminal methionine.

[0062] The present invention thus includes nucleic acid molecules and sequences which encode fusion proteins comprising one or more S. pneumoniae polypeptides of the present invention fused to an amino acid sequence which allows for post-translational modification to enhance immunogenicity. This post-translational modification may occur either in vitro or when the fusion protein is expressed in vivo in a host cell. An example of such a modification is the introduction of an amino acid sequence which results in the attachment of a lipid moiety.

[0063] Thus, as indicated above, the present invention includes genetic fusions wherein a S. pneumoniae nucleic acid sequence identified in Table 1 is linked to a nucleotide sequence encoding another amino acid sequence. These other amino acid sequences may be of streptococcal origin (e.g., another sequence selected from Table 1) or non-streptococcal origin.

[0064] The present invention further relates to variants of the nucleic acid molecules of the present invention, which encode portions, analogs or derivatives of the S. pneumoniae polypeptides described in Table 1. Variants may occur naturally, such as a natural allelic variant. By an "allelic variant" is intended one of several alternate forms of a gene occupying a given locus on a chromosome of an organism (Genes II, Lewin, B., ed., John Wiley & Sons, New York (1985)). Non-naturally occurring variants may be produced using art-known mutagenesis techniques.

[0065] Such variants include those produced by nucleotide substitutions, deletions or additions. The substitutions, deletions or additions may involve one or more nucleotides. These variants may be altered in coding regions, non-coding regions, or both. Alterations in the coding regions may produce conservative or non-conservative amino acid substitutions, deletions or additions. Especially preferred among these are silent substitutions, additions and deletions, which do not alter the properties and activities of the S. pneumoniae polypeptides disclosed herein or portions thereof. Silent substitution are most likely to be made in non-epitopic regions. Guidance regarding those regions containing epitopes is provided herein, for example, in Table 2. Also especially preferred in this regard are conservative substitutions.

[0066] Further embodiments of the invention include isolated nucleic acid molecules comprising a polynucleotide having a nucleotide sequence at least 90% identical, and more preferably at least 95%, 96%, 97%, 98% or 99% identical to: (a) a nucleotide sequence encoding any of the amino acid sequences of the polypeptides identified in Table 1; and (b) a nucleotide sequence complementary to any of the nucleotide sequences in (a) above.

[0067] By a polynucleotide having a nucleotide sequence at least, for example, 95% "identical" to a reference nucleotide sequence encoding a S. pneumoniae polypeptide described in Table 1, is intended that the nucleotide sequence of the polynucleotide is identical to the reference sequence except that the polynucleotide sequence may include up to five point mutations per each 100 nucleotides of the reference nucleotide sequence encoding the subject S. pneumoniae polypeptide. In other words, to obtain a polynucleotide having a nucleotide sequence at least 95% identical to a reference nucleotide sequence, up to 5% of the nucleotides in the reference sequence may be deleted or substituted with another nucleotide, or a number of nucleotides up to 5% of the total nucleotides in the reference sequence may be inserted into the reference sequence. These mutations of the reference sequence may occur at the 5' or 3' terminal positions of the reference nucleotide sequence or anywhere between those terminal positions, interspersed either individually among nucleotides in the reference sequence or in one or more contiguous groups within the reference sequence.

[0068] Certain nucleotides within some of the nucleic acid sequences shown in Table 1 were ambiguous upon sequencing. Completely unknown sequences are shown as an "N". Other unresolved nucleotides are known to be either a purine, shown as "R", or a pyrimidine, shown as "Y". Accordingly, when determining identity between two nucleotide sequences, identity is met where any nucleotide, including an "R", "Y" or "N", is found in a test sequence and at the corresponding position in the reference sequence (from Table 1). Likewise, an A, G or "R" in a test sequence is identical to an "R" in the reference sequence; and a T, C or "Y" in a test sequence is identical to a "Y" in the reference sequence.

[0069] As a practical matter, whether any particular nucleic acid molecule is at least 90%, 95%, 96%, 97%, 98% or 99% identical to, for instance, a nucleotide sequence described in Table 1 can be determined conventionally using known computer programs such as the Bestfit program (Wisconsin Sequence Analysis Package, Version 8 for Unix, Genetics Computer Group, University Research Park, 575 Science Drive, Madison, Wis. 53711). Bestfit uses the local homology algorithm of Smith and Waterman (Advances in Applied Mathematics 2:482-489 (1981)), to find the best segment of homology between two sequences. When using Bestfit or any other sequence alignment program to determine whether a particular sequence is, for instance, 95% identical to a reference sequence according to the present invention, the parameters are set, of course, such that the percentage of identity is calculated over the full length of the reference nucleotide sequence and that gaps in homology of up to 5% of the total number of nucleotides in the reference sequence are allowed.

[0070] The present application is directed to nucleic acid molecules at least 90%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequences described in Table 1. One of skill in the art would still know how to use the nucleic acid molecule, for instance, as a hybridization probe or a polymerase chain reaction (PCR) primer. Uses of the nucleic acid molecules of the present invention include, inter alia, (1) isolating Streptococcal genes or allelic variants thereof from either a genomic or cDNA library and (2) Northern Blot or PCR analysis for detecting Streptococcal mRNA expression.

[0071] Of course, due to the degeneracy of the genetic code, one of ordinary skill in the art will immediately recognize that a large number of nucleic acid molecules having a sequence at least 90%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence identified in Table 1 will encode the same polypeptide. In fact, since degenerate variants of these nucleotide sequences all encode the same polypeptide, this will be clear to the skilled artisan even without performing the above described comparison assay.

[0072] It will be further recognized in the art that, for such nucleic acid molecules that are not degenerate variants, a reasonable number will also encode proteins having antigenic epitopes of the S. pneumoniae polypeptides of the present invention. This is because the skilled artisan is fully aware of amino acid substitutions that are either less likely or not likely to significantly effect the antigenicity of a polypeptide (e.g., replacement of an amino acid in a region which is not believed to form an antigenic epitope). For example, since antigenic epitopes have been identified which contain as few as six amino acids (see Harlow, et al., Antibodies: A Laboratory Manual, 2nd Ed.; Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1988), page 76), in instances where a polypeptide has multiple antigenic epitopes the alteration of several amino acid residues would often not be expected to eliminate all of the antigenic epitopes of that polypeptide. This is especially so when the alterations are in regions believed to not constitute antigenic epitopes.

Vectors and Host Cells

[0073] The present invention also relates to vectors which include the isolated DNA molecules of the present invention, host cells which are genetically engineered with the recombinant vectors, and the production of S. pneumoniae polypeptides or fragments thereof by recombinant techniques.

[0074] Recombinant constructs may be introduced into host cells using well known techniques such as infection, transduction, transfection, transvection, electroporation and transformation. The vector may be, for example, a phage, plasmid, viral or retroviral vector. Retroviral vectors may be replication competent or replication defective. In the latter case, viral propagation generally will occur only in complementing host cells.

[0075] The polynucleotides may be joined to a vector containing a selectable marker for propagation in a host. Generally, a plasmid vector is introduced in a precipitate, such as a calcium phosphate precipitate, or in a complex with a charged lipid. If the vector is a virus, it may be packaged in vitro using an appropriate packaging cell line and then transduced into host cells.

[0076] Preferred are vectors comprising cis-acting control regions to the polynucleotide of interest. Appropriate trans-acting factors may be supplied by the host, supplied by a complementing vector or supplied by the vector itself upon introduction into the host.

[0077] In certain preferred embodiments in this regard, the vectors provide for specific expression, which may be inducible and/or cell type-specific. Particularly preferred among such vectors are those inducible by environmental factors that are easy to manipulate, such as temperature and nutrient additives.

[0078] Expression vectors useful in the present invention include chromosomal-, episomal- and virus-derived vectors, e.g., vectors derived from bacterial plasmids, bacteriophage, yeast episomes, yeast chromosomal elements, viruses such as baculoviruses, papova viruses, vaccinia viruses, adenoviruses, fowl pox viruses, pseudorabies viruses and retroviruses, and vectors derived from combinations thereof, such as cosmids and phagemids.

[0079] The DNA insert should be operatively linked to an appropriate promoter, such as the phage lambda PL promoter, the E. coli lac, trp and tac promoters, the SV40 early and late promoters and promoters of retroviral LTRs, to name a few. Other suitable promoters will be known to the skilled artisan. The expression constructs will further contain sites for transcription initiation, termination and, in the transcribed region, a ribosome binding site for translation. The coding portion of the mature transcripts expressed by the constructs will preferably include a translation initiating site at the beginning and a termination codon (UAA, UGA or UAG) appropriately positioned at the end of the polypeptide to be translated.

[0080] As indicated, the expression vectors will preferably include at least one selectable marker. Such markers include dihydrofolate reductase or neomycin resistance for eukaryotic cell culture and tetracycline or ampicillin resistance genes for culturing in E. coli and other bacteria. Representative examples of appropriate hosts include, but are not limited to, bacterial cells, such as E. coli, Streptomyces and Salmonella typhimurium cells; fungal cells, such as yeast cells; insect cells such as Drosophila S2 and Spodoptera Sf9 cells; animal cells such as CHO, COS and Bowes melanoma cells; and plant cells. Appropriate culture mediums and conditions for the above-described host cells are known in the art.

[0081] Among vectors preferred for use in bacteria include pQE70, pQE60 and pQE-9, available from Qiagen; pBS vectors, Phagescript vectors, Bluescript vectors, pNH8A, pNH16a, pNH18A, pNH46A available from Stratagene; pET series of vectors available from Novagen; and ptrc99a, pKK223-3, pKK233-3, pDR540, pRIT5 available from Pharmacia. Among preferred eukaryotic vectors are pWLNEO, pSV2CAT, pOG44, pXT1 and pSG available from Stratagene; and pSVK3, pBPV, pMSG and pSVL available from Pharmacia. Other suitable vectors will be readily apparent to the skilled artisan.

[0082] Among known bacterial promoters suitable for use in the present invention include the E. coli lad and lacZ promoters, the T3 and T7 promoters, the gpt promoter, the lambda PR and PL promoters and the trp promoter. Suitable eukaryotic promoters include the CMV immediate early promoter, the HSV thymidine kinase promoter, the early and late SV40 promoters, the promoters of retroviral LTRs, such as those of the Rous sarcoma virus (RSV), and metallothionein promoters, such as the mouse metallothionein-I promoter.

[0083] Introduction of the construct into the host cell can be effected by calcium phosphate transfection, DEAE-dextran mediated transfection, cationic lipid-mediated transfection, electroporation, transduction, infection or other methods. Such methods are described in many standard laboratory manuals (for example, Davis, et al., Basic Methods In Molecular Biology (1986)).

[0084] Transcription of DNA encoding the polypeptides of the present invention by higher eukaryotes may be increased by inserting an enhancer sequence into the vector. Enhancers are cis-acting elements of DNA, usually about from 10 to 300 by that act to increase transcriptional activity of a promoter in a given host cell-type. Examples of enhancers include the SV40 enhancer, which is located on the late side of the replication origin at by 100 to 270, the cytomegalovirus early promoter enhancer, the polyoma enhancer on the late side of the replication origin, and adenovirus enhancers.

[0085] For secretion of the translated polypeptide into the lumen of the endoplasmic reticulum, into the periplasmic space or into the extracellular environment, appropriate secretion signals may be incorporated into the expressed polypeptide. The signals may be endogenous to the polypeptide or they may be heterologous signals.

[0086] The polypeptide may be expressed in a modified form, such as a fusion protein, and may include not only secretion signals, but also additional heterologous functional regions. For instance, a region of additional amino acids, particularly charged amino acids, may be added to the N-terminus of the polypeptide to improve stability and persistence in the host cell, during purification, or during subsequent handling and storage. Also, peptide moieties may be added to the polypeptide to facilitate purification. Such regions may be removed prior to final preparation of the polypeptide. The addition of peptide moieties to polypeptides to engender secretion or excretion, to improve stability and to facilitate purification, among others, are familiar and routine techniques in the art. A preferred fusion protein comprises a heterologous region from immunoglobulin that is useful to solubilize proteins. For example, EP-A-O 464 533 (Canadian counterpart 2045869) discloses fusion proteins comprising various portions of constant region of immunoglobin molecules together with another human protein or part thereof. In many cases, the Fc part in a fusion protein is thoroughly advantageous for use in therapy and diagnosis and thus results, for example, in improved pharmacokinetic properties (EP-A 0232 262). On the other hand, for some uses it would be desirable to be able to delete the Fc part after the fusion protein has been expressed, detected and purified in the advantageous manner described. This is the case when Fc portion proves to be a hindrance to use in therapy and diagnosis, for example when the fusion protein is to be used as antigen for immunizations. In drug discovery, for example, human proteins, such as, hIL5-receptor has been fused with Fc portions for the purpose of high-throughput screening assays to identify antagonists of hIL-5 See Bennett, D. et al., J. Molec. Recogn. 8:52-58 (1995) and Johanson, K. et al., J. Biol. Chem. 270 (16):9459-9471 (1995).

[0087] The S. pneumoniae polypeptides can be recovered and purified from recombinant cell cultures by well-known methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxylapatite chromatography, lectin chromatography and high performance liquid chromatography ("HPLC") is employed for purification. Polypeptides of the present invention include naturally purified products, products of chemical synthetic procedures, and products produced by recombinant techniques from a prokaryotic or eukaryotic host, including, for example, bacterial, yeast, higher plant, insect and mammalian cells.

Polypeptides and Fragments

[0088] The invention further provides isolated polypeptides having the amino acid sequences described in Table 1, and shown as SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, and so on through SEQ ID NO:226, and peptides or polypeptides comprising portions of the above polypeptides. The terms "peptide" and "oligopeptide" are considered synonymous (as is commonly recognized) and each term can be used interchangeably as the context requires to indicate a chain of at least two amino acids coupled by peptidyl linkages. The word "polypeptide" is used herein for chains containing more than ten amino acid residues. All oligopeptide and polypeptide formulas or sequences herein are written from left to right and in the direction from amino terminus to carboxy terminus.

[0089] Some amino acid sequences of the S. pneumoniae polypeptides described in Table 1 can be varied without significantly effecting the antigenicity of the polypeptides. If such differences in sequence are contemplated, it should be remembered that there will be critical areas on the polypeptide which determine antigenicity. In general, it is possible to replace residues which do not form part of an antigenic epitope without significantly effecting the antigenicity of a polypeptide. Guidance for such alterations is given in Table 2 wherein epitopes for each polypeptide is delineated.

[0090] The polypeptides of the present invention are preferably provided in an isolated form. By "isolated polypeptide" is intended a polypeptide removed from its native environment. Thus, a polypeptide produced and/or contained within a recombinant host cell is considered isolated for purposes of the present invention. Also intended as an "isolated polypeptide" is a polypeptide that has been purified, partially or substantially, from a recombinant host cell. For example, recombinantly produced versions of the S. pneumoniae polypeptides described in Table 1 can be substantially purified by the one-step method described by Smith and Johnson (Gene 67:31-40 (1988)).

[0091] The polypeptides of the present invention include: (a) an amino acid sequence of any of the polypeptides described in Table 1; and (b) an amino acid sequence of an epitope-bearing portion of any one of the polypeptides of (a); as well as polypeptides with at least 70% similarity, and more preferably at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% similarity to those described in (a) or (b) above, as well as polypeptides having an amino acid sequence at least 70% identical, more preferably at least 75% identical, and still more preferably 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to those above.

[0092] By "% similarity" for two polypeptides is intended a similarity score produced by comparing the amino acid sequences of the two polypeptides using the Bestfit program (Wisconsin Sequence Analysis Package, Version 8 for Unix, Genetics Computer Group, University Research Park, 575 Science Drive, Madison, Wis. 53711) and the default settings for determining similarity. Bestfit uses the local homology algorithm of Smith and Waterman (Advances in Applied Mathematics 2:482-489 (1981)) to find the best segment of similarity between two sequences.

[0093] By a polypeptide having an amino acid sequence at least, for example, 95% "identical" to a reference amino acid sequence of a S. pneumoniae polypeptide is intended that the amino acid sequence of the polypeptide is identical to the reference sequence except that the polypeptide sequence may include up to five amino acid alterations per each 100 amino acids of the reference amino acid sequence. In other words, to obtain a polypeptide having an amino acid sequence at least 95% identical to a reference amino acid sequence, up to 5% of the amino acid residues in the reference sequence may be deleted or substituted with another amino acid, or a number of amino acids up to 5% of the total amino acid residues in the reference sequence may be inserted into the reference sequence. These alterations of the reference sequence may occur at the amino or carboxy terminal positions of the reference amino acid sequence or anywhere between those terminal positions, interspersed either individually among residues in the reference sequence or in one or more contiguous groups within the reference sequence.

[0094] The amino acid sequences shown in Table 1 may have on or more "X" residues. "X" represents unknown. Thus, for purposes of defining identity, if any amino acid is present at the same position in a reference amino acid sequence (shown in Table 1) where an X is shown, the two sequences are identical at that position.

[0095] As a practical matter, whether any particular polypeptide is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to, for instance, an amino acid sequence shown in Table 1, can be determined conventionally using known computer programs such the Bestfit program (Wisconsin Sequence Analysis Package, Version 8 for Unix, Genetics Computer Group, University Research Park, 575 Science Drive, Madison, Wis. 53711). When using Bestfit or any other sequence alignment program to determine whether a particular sequence is, for instance, 95% identical to a reference sequence according to the present invention, the parameters are set, of course, such that the percentage of identity is calculated over the full length of the reference amino acid sequence and that gaps in homology of up to 5% of the total number of amino acid residues in the reference sequence are allowed.

[0096] As described below, the polypeptides of the present invention can also be used to raise polyclonal and monoclonal antibodies, which are useful in assays for detecting Streptococcal protein expression.

[0097] In another aspect, the invention provides peptides and polypeptides comprising epitope-bearing portions of the S. pneumoniae polypeptides of the invention. These epitopes are immunogenic or antigenic epitopes of the polypeptides of the invention. An "immunogenic epitope" is defined as a part of a protein that elicits an antibody response when the whole protein or polypeptide is the immunogen. These immunogenic epitopes are believed to be confined to a few loci on the molecule. On the other hand, a region of a protein molecule to which an antibody can bind is defined as an "antigenic determinant" or "antigenic epitope." The number of immunogenic epitopes of a protein generally is less than the number of antigenic epitopes (Geysen, et al., Proc. Natl. Acad. Sci. USA 81:3998-4002 (1983)). Predicted antigenic epitopes are shown in Table 2, below.

[0098] As to the selection of peptides or polypeptides bearing an antigenic epitope (i.e., that contain a region of a protein molecule to which an antibody can bind), it is well known in that art that relatively short synthetic peptides that mimic part of a protein sequence are routinely capable of eliciting an antiserum that reacts with the partially mimicked protein (for instance, Sutcliffe, J., et al., Science 219:660-666 (1983)). Peptides capable of eliciting protein-reactive sera are frequently represented in the primary sequence of a protein, can be characterized by a set of simple chemical rules, and are confined neither to immunodominant regions of intact proteins (i.e., immunogenic epitopes) nor to the amino or carboxyl terminals. Peptides that are extremely hydrophobic and those of six or fewer residues generally are ineffective at inducing antibodies that bind to the mimicked protein; longer, peptides, especially those containing proline residues, usually are effective (Sutcliffe, et al., supra, p. 661). For instance, 18 of 20 peptides designed according to these guidelines, containing 8-39 residues covering 75% of the sequence of the influenza virus hemagglutinin HA1 polypeptide chain, induced antibodies that reacted with the HA1 protein or intact virus; and 12/12 peptides from the MuLV polymerase and 18/18 from the rabies glycoprotein induced antibodies that precipitated the respective proteins.

[0099] Antigenic epitope-bearing peptides and polypeptides of the invention are therefore useful to raise antibodies, including monoclonal antibodies, that bind specifically to a polypeptide of the invention. Thus, a high proportion of hybridomas obtained by fusion of spleen cells from donors immunized with an antigen epitope-bearing peptide generally secrete antibody reactive with the native protein (Sutcliffe, et al., supra, p. 663). The antibodies raised by antigenic epitope-bearing peptides or polypeptides are useful to detect the mimicked protein, and antibodies to different peptides may be used for tracking the fate of various regions of a protein precursor which undergoes post-translational processing. The peptides and anti-peptide antibodies may be used in a variety of qualitative or quantitative assays for the mimicked protein, for instance in competition assays since it has been shown that even short peptides (e.g., about 9 amino acids) can bind and displace the larger peptides in immunoprecipitation assays (for instance, Wilson, et al., Cell 37:767-778 (1984) p. 777). The anti-peptide antibodies of the invention also are useful for purification of the mimicked protein, for instance, by adsorption chromatography using methods well known in the art.

[0100] Antigenic epitope-bearing peptides and polypeptides of the invention designed according to the above guidelines preferably contain a sequence of at least seven, more preferably at least nine and most preferably between about 15 to about 30 amino acids contained within the amino acid sequence of a polypeptide of the invention. However, peptides or polypeptides comprising a larger portion of an amino acid sequence of a polypeptide of the invention, containing about 30 to about 50 amino acids, or any length up to and including the entire amino acid sequence of a polypeptide of the invention, also are considered epitope-bearing peptides or polypeptides of the invention and also are useful for inducing antibodies that react with the mimicked protein. Preferably, the amino acid sequence of the epitope-bearing peptide is selected to provide substantial solubility in aqueous solvents (i.e., the sequence includes relatively hydrophilic residues and highly hydrophobic sequences are preferably avoided); and sequences containing proline residues are particularly preferred.

[0101] Non-limiting examples of antigenic polypeptides or peptides that can be used to generate Streptococcal-specific antibodies include portions of the amino acid sequences identified in Table 1. More specifically, Table 2 discloses antigenic fragments of polypeptides of the present invention, which antigenic fragments comprise amino acid sequences from about the first amino acid residues indicated to about the last amino acid residue indicated for each fragment. The polypeptide fragments disclosed in Table 2 are believed to be antigenic regions of the S. pneumoniae polypeptides described in Table 1. Thus the invention further includes isolated peptides and polypeptides comprising an amino acid sequence of an epitope shown in Table 2 and polynucleotides encoding said polypeptides.

[0102] The epitope-bearing peptides and polypeptides of the invention may be produced by any conventional means for making peptides or polypeptides including recombinant means using nucleic acid molecules of the invention. For instance, an epitope-bearing amino acid sequence of the present invention may be fused to a larger polypeptide which acts as a carrier during recombinant production and purification, as well as during immunization to produce anti-peptide antibodies. Epitope-bearing peptides also may be synthesized using known methods of chemical synthesis. For instance, Houghten has described a simple method for synthesis of large numbers of peptides, such as 10-20 mg of 248 different 13 residue peptides representing single amino acid variants of a segment of the HA1 polypeptide which were prepared and characterized (by ELISA-type binding studies) in less than four weeks (Houghten, R. A. Proc. Natl. Acad. Sci. USA 82:5131-5135 (1985)). This "Simultaneous Multiple Peptide Synthesis (SMPS)" process is further described in U.S. Pat. No. 4,631,211 to Houghten and coworkers (1986). In this procedure the individual resins for the solid-phase synthesis of various peptides are contained in separate solvent-permeable packets, enabling the optimal use of the many identical repetitive steps involved in solid-phase methods. A completely manual procedure allows 500-1000 or more syntheses to be conducted simultaneously (Houghten, et al., supra, p. 5134).

[0103] Epitope-bearing peptides and polypeptides of the invention are used to induce antibodies according to methods well known in the art (for instance, Sutcliffe, et al., supra; Wilson, et al., supra; Chow, M., et al., Proc. Natl. Acad. Sci. USA 82:910-914; and Bittle, F. J., et al., J. Gen. Virol. 66:2347-2354 (1985)). Generally, animals may be immunized with free peptide; however, anti-peptide antibody titer may be boosted by coupling of the peptide to a macromolecular carrier, such as keyhole limpet hemacyanin (KLH) or tetanus toxoid. For instance, peptides containing cysteine may be coupled to carrier using a linker such as m-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS), while other peptides may be coupled to carrier using a more general linking agent such as glutaraldehyde. Animals such as rabbits, rats and mice are immunized with either free or carrier-coupled peptides, for instance, by intraperitoneal and/or intradermal injection of emulsions containing about 100 .mu.g peptide or carrier protein and Freund's adjuvant. Several booster injections may be needed, for instance, at intervals of about two weeks, to provide a useful titer of anti-peptide antibody which can be detected, for example, by ELISA assay using free peptide adsorbed to a solid surface. The titer of anti-peptide antibodies in serum from an immunized animal may be increased by selection of anti-peptide antibodies, for instance, by adsorption to the peptide on a solid support and elution of the selected antibodies according to methods well known in the art.

[0104] Immunogenic epitope-bearing peptides of the invention, i.e., those parts of a protein that elicit an antibody response when the whole protein is the immunogen, are identified according to methods known in the art. For instance, Geysen, et al., supra, discloses a procedure for rapid concurrent synthesis on solid supports of hundreds of peptides of sufficient purity to react in an enzyme-linked immunosorbent assay. Interaction of synthesized peptides with antibodies is then easily detected without removing them from the support. In this manner a peptide bearing an immunogenic epitope of a desired protein may be identified routinely by one of ordinary skill in the art. For instance, the immunologically important epitope in the coat protein of foot-and-mouth disease virus was located by Geysen et al. supra with a resolution of seven amino acids by synthesis of an overlapping set of all 208 possible hexapeptides covering the entire 213 amino acid sequence of the protein. Then, a complete replacement set of peptides in which all 20 amino acids were substituted in turn at every position within the epitope were synthesized, and the particular amino acids conferring specificity for the reaction with antibody were determined. Thus, peptide analogs of the epitope-bearing peptides of the invention can be made routinely by this method. U.S. Pat. No. 4,708,781 to Geysen (1987) further describes this method of identifying a peptide bearing an immunogenic epitope of a desired protein.

[0105] Further still, U.S. Pat. No. 5,194,392, to Geysen (1990), describes a general method of detecting or determining the sequence of monomers (amino acids or other compounds) which is a topological equivalent of the epitope (i.e., a "mimotope") which is complementary to a particular paratope (antigen binding site) of an antibody of interest. More generally, U.S. Pat. No. 4,433,092, also to Geysen (1989), describes a method of detecting or determining a sequence of monomers which is a topographical equivalent of a ligand which is complementary to the ligand binding site of a particular receptor of interest. Similarly, U.S. Pat. No. 5,480,971 to Houghten, R. A. et al. (1996) discloses linear C.sub.1-C.sub.7-alkyl peralkylated oligopeptides and sets and libraries of such peptides, as well as methods for using such oligopeptide sets and libraries for determining the sequence of a peralkylated oligopeptide that preferentially binds to an acceptor molecule of interest. Thus, non-peptide analogs of the epitope-bearing peptides of the invention also can be made routinely by these methods.

[0106] The entire disclosure of each document cited in this section on "Polypeptides and Fragments" is hereby incorporated herein by reference.

[0107] As one of skill in the art will appreciate, the polypeptides of the present invention and the epitope-bearing fragments thereof described above can be combined with parts of the constant domain of immunoglobulins (IgG), resulting in chimeric polypeptides. These fusion proteins facilitate purification and show an increased half-life in vivo. This has been shown, e.g., for chimeric proteins consisting of the first two domains of the human CD4-polypeptide and various domains of the constant regions of the heavy or light chains of mammalian immunoglobulins (EPA 0,394,827; Traunecker et al., Nature 331:84-86 (1988)). Fusion proteins that have a disulfide-linked dimeric structure due to the IgG part can also be more efficient in binding and neutralizing other molecules than a monomeric S. pneumoniae polypeptide or fragment thereof alone (Fountoulakis et al., J. Biochem. 270:3958-3964 (1995)).

Diagnostic Assays

[0108] The present invention further relates to a method for assaying for Streptococcal infection in an animal via detecting the expression of genes encoding Streptococcal polypeptides (e.g., the polypeptides described Table 1). This method comprises analyzing tissue or body fluid from the animal for Streptococcus-specific antibodies or Streptococcal nucleic acids or proteins. Analysis of nucleic acid specific to Streptococcus can be done by PCR or hybridization techniques using nucleic acid sequences of the present invention as either hybridization probes or primers (cf. Molecular Cloning: A Laboratory Manual, second edition, edited by Sambrook, Fritsch, & Maniatis, Cold Spring Harbor Laboratory, 1989; Eremeeva et al., J. Clin. Microbiol. 32:803-810 (1994) which describes differentiation among spotted fever group Rickettsiae species by analysis of restriction fragment length polymorphism of PCR-amplified DNA). Methods for detecting B. burgdorferi nucleic acids via PCR are described, for example, in Chen et al., J. Clin. Microbiol. 32:589-595 (1994).

[0109] Where diagnosis of a disease state related to infection with Streptococcus has already been made, the present invention is useful for monitoring progression or regression of the disease state whereby patients exhibiting enhanced Streptococcus gene expression will experience a worse clinical outcome relative to patients expressing these gene(s) at a lower level.

[0110] By "assaying for Streptococcal infection in an animal via detection of genes encoding Streptococcal polypeptides" is intended qualitatively or quantitatively measuring or estimating the level of one or more Streptococcus polypeptides or the level of nucleic acid encoding Streptococcus polypeptides in a first biological sample either directly (e.g., by determining or estimating absolute protein level or nucleic level) or relatively (e.g., by comparing to the Streptococcus polypeptide level or mRNA level in a second biological sample). The Streptococcus polypeptide level or nucleic acid level in the second sample used for a relative comparison may be undetectable if obtained from an animal which is not infected with Streptococcus. When monitoring the progression or regression of a disease state, the Streptococcus polypeptide level or nucleic acid level may be compared to a second sample obtained from either an animal infected with Streptococcus or the same animal from which the first sample was obtained but taken from that animal at a different time than the first. As will be appreciated in the art, once a standard Streptococcus polypeptide level or nucleic acid level which corresponds to a particular stage of a Streptococcus infection is known, it can be used repeatedly as a standard for comparison.

[0111] By "biological sample" is intended any biological sample obtained from an animal, cell line, tissue culture, or other source which contains Streptococcus polypeptide, mRNA, or DNA. Biological samples include body fluids (such as plasma and synovial fluid) which contain Streptococcus polypeptides, and muscle, skin, and cartilage tissues. Methods for obtaining tissue biopsies and body fluids are well known in the art.

[0112] The present invention is useful for detecting diseases related to Streptococcus infections in animals. Preferred animals include monkeys, apes, cats, dogs, cows, pigs, mice, horses, rabbits and humans. Particularly preferred are humans.

[0113] Total RNA can be isolated from a biological sample using any suitable technique such as the single-step guanidinium-thiocyanate-phenol-chloroform method described in Chomczynski and Sacchi, Anal. Biochem. 162:156-159 (1987). mRNA encoding Streptococcus polypeptides having sufficient homology to the nucleic acid sequences identified in Table 1 to allow for hybridization between complementary sequences are then assayed using any appropriate method. These include Northern blot analysis, S1 nuclease mapping, the polymerase chain reaction (PCR), reverse transcription in combination with the polymerase chain reaction (RT-PCR), and reverse transcription in combination with the ligase chain reaction (RT-LCR).

[0114] Northern blot analysis can be performed as described in Harada et al., Cell 63:303-312 (1990). Briefly, total RNA is prepared from a biological sample as described above. For the Northern blot, the RNA is denatured in an appropriate buffer (such as glyoxal/dimethyl sulfoxide/sodium phosphate buffer), subjected to agarose gel electrophoresis, and transferred onto a nitrocellulose filter. After the RNAs have been linked to the filter by a UV linker, the filter is prehybridized in a solution containing formamide, SSC, Denhardt's solution, denatured salmon sperm, SDS, and sodium phosphate buffer. A S. pneumoniae polypeptide DNA sequence shown in Table 1 labeled according to any appropriate method (such as the .sup.32P-multiprimed DNA labeling system (Amersham)) is used as probe. After hybridization overnight, the filter is washed and exposed to x-ray film. DNA for use as probe according to the present invention is described in the sections above and will preferably at least 15 by in length.

[0115] S1 mapping can be performed as described in Fujita et al., Cell 49:357-367 (1987). To prepare probe DNA for use in S1 mapping, the sense strand of an above-described S. pneumoniae DNA sequence of the present invention is used as a template to synthesize labeled antisense DNA. The antisense DNA can then be digested using an appropriate restriction endonuclease to generate further DNA probes of a desired length. Such antisense probes are useful for visualizing protected bands corresponding to the target mRNA (i.e., mRNA encoding Streptococcus polypeptides).

[0116] Preferably, levels of mRNA encoding Streptococcus polypeptides are assayed using the RT-PCR method described in Makino et al., Technique 2:295-301 (1990). By this method, the radioactivities of the "amplicons" in the polyacrylamide gel bands are linearly related to the initial concentration of the target mRNA. Briefly, this method involves adding total RNA isolated from a biological sample in a reaction mixture containing a RT primer and appropriate buffer. After incubating for primer annealing, the mixture can be supplemented with a RT buffer, dNTPs, DTT, RNase inhibitor and reverse transcriptase. After incubation to achieve reverse transcription of the RNA, the RT products are then subject to PCR using labeled primers. Alternatively, rather than labeling the primers, a labeled dNTP can be included in the PCR reaction mixture. PCR amplification can be performed in a DNA thermal cycler according to conventional techniques. After a suitable number of rounds to achieve amplification, the PCR reaction mixture is electrophoresed on a polyacrylamide gel. After drying the gel, the radioactivity of the appropriate bands (corresponding to the mRNA encoding the Streptococcus polypeptides)) is quantified using an imaging analyzer. RT and PCR reaction ingredients and conditions, reagent and gel concentrations, and labeling methods are well known in the art. Variations on the RT-PCR method will be apparent to the skilled artisan.

[0117] Assaying Streptococcus polypeptide levels in a biological sample can occur using any art-known method. Preferred for assaying Streptococcus polypeptide levels in a biological sample are antibody-based techniques. For example, Streptococcus polypeptide expression in tissues can be studied with classical immunohistological methods. In these, the specific recognition is provided by the primary antibody (polyclonal or monoclonal) but the secondary detection system can utilize fluorescent, enzyme, or other conjugated secondary antibodies. As a result, an immunohistological staining of tissue section for pathological examination is obtained. Tissues can also be extracted, e.g., with urea and neutral detergent, for the liberation of Streptococcus polypeptides for Western-blot or dot/slot assay (Jalkanen, M., et al., J. Cell. Biol. 101:976-985 (1985); Jalkanen, M., et al., J. Cell. Biol. 105:3087-3096 (1987)). In this technique, which is based on the use of cationic solid phases, quantitation of a Streptococcus polypeptide can be accomplished using an isolated Streptococcus polypeptide as a standard. This technique can also be applied to body fluids.

[0118] Other antibody-based methods useful for detecting Streptococcus polypeptide gene expression include immunoassays, such as the enzyme linked immunosorbent assay (ELISA) and the radioimmunoassay (RIA). For example, a Streptococcus polypeptide-specific monoclonal antibodies can be used both as an immunoabsorbent and as an enzyme-labeled probe to detect and quantify a Streptococcus polypeptide. The amount of a Streptococcus polypeptide present in the sample can be calculated by reference to the amount present in a standard preparation using a linear regression computer algorithm. Such an ELISA for detecting a tumor antigen is described in Iacobelli et al., Breast Cancer Research and Treatment 11:19-30 (1988). In another ELISA assay, two distinct specific monoclonal antibodies can be used to detect Streptococcus polypeptides in a body fluid. In this assay, one of the antibodies is used as the immunoabsorbent and the other as the enzyme-labeled probe.

[0119] The above techniques may be conducted essentially as a "one-step" or "two-step" assay. The "one-step" assay involves contacting the Streptococcus polypeptide with immobilized antibody and, without washing, contacting the mixture with the labeled antibody. The "two-step" assay involves washing before contacting the mixture with the labeled antibody. Other conventional methods may also be employed as suitable. It is usually desirable to immobilize one component of the assay system on a support, thereby allowing other components of the system to be brought into contact with the component and readily removed from the sample.

[0120] Streptococcus polypeptide-specific antibodies for use in the present invention can be raised against an intact S. pneumoniae polypeptide of the present invention or fragment thereof. These polypeptides and fragments may be administered to an animal (e.g., rabbit or mouse) either with a carrier protein (e.g., albumin) or, if long enough (e.g., at least about 25 amino acids), without a carrier.

[0121] As used herein, the term "antibody" (Ab) or "monoclonal antibody" (Mab) is meant to include intact molecules as well as antibody fragments (such as, for example, Fab and F(ab').sub.2 fragments) which are capable of specifically binding to a Streptococcus polypeptide. Fab and F(ab').sub.2 fragments lack the Fc fragment of intact antibody, clear more rapidly from the circulation, and may have less non-specific tissue binding of an intact antibody (Wahl et al., J. Nucl. Med. 24:316-325 (1983)). Thus, these fragments are preferred.

[0122] The antibodies of the present invention may be prepared by any of a variety of methods. For example, the S. pneumoniae polypeptides identified in Table 1, or fragments thereof, can be administered to an animal in order to induce the production of sera containing polyclonal antibodies. In a preferred method, a preparation of a S. pneumoniae polypeptide of the present invention is prepared and purified to render it substantially free of natural contaminants. Such a preparation is then introduced into an animal in order to produce polyclonal antisera of high specific activity.

[0123] In the most preferred method, the antibodies of the present invention are monoclonal antibodies. Such monoclonal antibodies can be prepared using hybridoma technology (Kohler et al., Nature 256:495 (1975); Kohler et al., Eur. J. Immunol. 6:511 (1976); Kohler et al., Eur. J. Immunol. 6:292 (1976); Hammerling et al., In: Monoclonal Antibodies and T-Cell Hybridomas, Elsevier, N.Y., (1981) pp. 563-681). In general, such procedures involve immunizing an animal (preferably a mouse) with a S. pneumoniae polypeptide antigen of the present invention. Suitable cells can be recognized by their capacity to bind anti-Streptococcus polypeptide antibody. Such cells may be cultured in any suitable tissue culture medium; however, it is preferable to culture cells in Earle's modified Eagle's medium supplemented with 10% fetal bovine serum (inactivated at about 56.degree. C.), and supplemented with about 10 g/l of nonessential amino acids, about 1,000 U/ml of penicillin, and about 100 .mu.g/ml of streptomycin. The splenocytes of such mice are extracted and fused with a suitable myeloma cell line. Any suitable myeloma cell line may be employed in accordance with the present invention; however, it is preferable to employ the parent myeloma cell line (SP.sub.2O), available from the American Type Culture Collection, Rockville, Md. After fusion, the resulting hybridoma cells are selectively maintained in HAT medium, and then cloned by limiting dilution as described by Wands et al. (Gastroenterology 80:225-232 (1981)). The hybridoma cells obtained through such a selection are then assayed to identify clones which secrete antibodies capable of binding the Streptococcus polypeptide antigen administered to immunized animal.

[0124] Alternatively, additional antibodies capable of binding to Streptococcus polypeptide antigens may be produced in a two-step procedure through the use of anti-idiotypic antibodies. Such a method makes use of the fact that antibodies are themselves antigens, and that, therefore, it is possible to obtain an antibody which binds to a second antibody. In accordance with this method, Streptococcus polypeptide-specific antibodies are used to immunize an animal, preferably a mouse. The splenocytes of such an animal are then used to produce hybridoma cells, and the hybridoma cells are screened to identify clones which produce an antibody whose ability to bind to the Streptococcus polypeptide-specific antibody can be blocked by a Streptococcus polypeptide antigen. Such antibodies comprise anti-idiotypic antibodies to the Streptococcus polypeptide-specific antibody and can be used to immunize an animal to induce formation of further Streptococcus polypeptide-specific antibodies.

[0125] It will be appreciated that Fab and F(ab').sub.2 and other fragments of the antibodies of the present invention may be used according to the methods disclosed herein. Such fragments are typically produced by proteolytic cleavage, using enzymes such as papain (to produce Fab fragments) or pepsin (to produce F(ab').sub.2 fragments). Alternatively, Streptococcus polypeptide-binding fragments can be produced through the application of recombinant DNA technology or through synthetic chemistry.

[0126] Of special interest to the present invention are antibodies to Streptococcus polypeptide antigens which are produced in humans, or are "humanized" (i.e., non-immunogenic in a human) by recombinant or other technology. Humanized antibodies may be produced, for example by replacing an immunogenic portion of an antibody with a corresponding, but non-immunogenic portion (i.e., chimeric antibodies) (Robinson, R. R. et al., International Patent Publication PCT/US86/02269; Akira, K. et al., European Patent Application 184,187; Taniguchi, M., European Patent Application 171,496; Morrison, S. L. et al., European Patent Application 173,494; Neuberger, M. S. et al., PCT Application WO 86/01533; Cabilly, S. et al., European Patent Application 125,023; Better, M. et al., Science 240:1041-1043 (1988); Liu, A. Y. et al., Proc. Natl. Acad. Sci. USA 84:3439-3443 (1987); Liu, A. Y. et al., J. Immunol. 139:3521-3526 (1987); Sun, L. K. et al., Proc. Natl. Acad. Sci. USA 84:214-218 (1987); Nishimura, Y. et al., Canc. Res. 47:999-1005 (1987); Wood, C. R. et al., Nature 314:446-449 (1985)); Shaw et al., J. Natl. Cancer Inst. 80:1553-1559 (1988). General reviews of "humanized" chimeric antibodies are provided by Morrison, S. L. (Science, 229:1202-1207 (1985)) and by Oi, V. T. et al., BioTechniques 4:214 (1986)). Suitable "humanized" antibodies can be alternatively produced by CDR or CEA substitution (Jones, P. T. et al., Nature 321:552-525 (1986); Verhoeyan et al., Science 239:1534 (1988); Beidler, C. B. et al., J. Immunol. 141:4053-4060 (1988)).

[0127] Suitable enzyme labels include, for example, those from the oxidase group, which catalyze the production of hydrogen peroxide by reacting with substrate. Glucose oxidase is particularly preferred as it has good stability and its substrate (glucose) is readily available. Activity of an oxidase label may be assayed by measuring the concentration of hydrogen peroxide formed by the enzyme-labeled antibody/substrate reaction. Besides enzymes, other suitable labels include radioisotopes, such as iodine (.sup.125I, .sup.121I), carbon (.sup.14C), sulphur (.sup.35S), tritium (.sup.3H), indium (.sup.112In), and technetium (.sup.99mTc), and fluorescent labels, such as fluorescein and rhodamine, and biotin.

[0128] Further suitable labels for the Streptococcus polypeptide-specific antibodies of the present invention are provided below. Examples of suitable enzyme labels include malate dehydrogenase, staphylococcal nuclease, delta-5-steroid isomerase, yeast-alcohol dehydrogenase, alpha-glycerol phosphate dehydrogenase, triose phosphate isomerase, peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-6-phosphate dehydrogenase, glucoamylase, and acetylcholine esterase.

[0129] Examples of suitable radioisotopic labels include .sup.3H, .sup.111In, .sup.125I, .sup.131I, .sup.32P, .sup.35S, .sup.14C, .sup.51Cr, .sup.57To, .sup.58Co, .sup.59Fe, .sup.75Se, .sup.152Eu, .sup.90Y, .sup.67Cu, .sup.217Ci, .sup.211At, .sup.212Pb, .sup.47Sc, .sup.109Pd, etc. .sup.111In is a preferred isotope where in vivo imaging is used since its avoids the problem of dehalogenation of the .sup.125I or .sup.131I-labeled monoclonal antibody by the liver. In addition, this radionucleotide has a more favorable gamma emission energy for imaging (Perkins et al., Eur. J. Nucl. Med. 10:296-301 (1985); Carasquillo et al., J. Nucl. Med. 28:281-287 (1987)). For example, .sup.111In coupled to monoclonal antibodies with 1-(P-isothiocyanatobenzyl)-DPTA has shown little uptake in non-tumorous tissues, particularly the liver, and therefore enhances specificity of tumor localization (Esteban et al., J. Nucl. Med. 28:861-870 (1987)).

[0130] Examples of suitable non-radioactive isotopic labels include .sup.157Gd, .sup.55Mn, .sup.162Dy, .sup.52Tr, and .sup.56Fe.

[0131] Examples of suitable fluorescent labels include an .sup.152Eu label, a fluorescein label, an isothiocyanate label, a rhodamine label, a phycoerythrin label, a phycocyanin label, an allophycocyanin label, an o-phthaldehyde label, and a fluorescamine label.

[0132] Examples of suitable toxin labels include diphtheria toxin, ricin, and cholera toxin.

[0133] Examples of chemiluminescent labels include a luminal label, an isoluminal label, an aromatic acridinium ester label, an imidazole label, an acridinium salt label, an oxalate ester label, a luciferin label, a luciferase label, and an aequorin label.

[0134] Examples of nuclear magnetic resonance contrasting agents include heavy metal nuclei such as Gd, Mn, and iron.

[0135] Typical techniques for binding the above-described labels to antibodies are provided by Kennedy et al., Clin. Chim. Acta 70:1-31 (1976), and Schurs et al., Clin. Chim. Acta 81:1-40 (1977). Coupling techniques mentioned in the latter are the glutaraldehyde method, the periodate method, the dimaleimide method, the m-maleimidobenzyl-N-hydroxy-succinimide ester method, all of which methods are incorporated by reference herein.

[0136] In a related aspect, the invention includes a diagnostic kit for use in screening serum containing antibodies specific against S. pneumoniae infection. Such a kit may include an isolated S. pneumoniae antigen comprising an epitope which is specifically immunoreactive with at least one anti-S. pneumoniae antibody. Such a kit also includes means for detecting the binding of said antibody to the antigen. In specific embodiments, the kit may include a recombinantly produced or chemically synthesized peptide or polypeptide antigen. The peptide or polypeptide antigen may be attached to a solid support.

[0137] In a more specific embodiment, the detecting means of the above-described kit includes a solid support to which said peptide or polypeptide antigen is attached. Such a kit may also include a non-attached reporter-labeled anti-human antibody. In this embodiment, binding of the antibody to the S. pneumoniae antigen can be detected by binding of the reporter labeled antibody to the anti-S. pneumoniae antibody.

[0138] In a related aspect, the invention includes a method of detecting S. pneumoniae infection in a subject. This detection method includes reacting a body fluid, preferably serum, from the subject with an isolated S. pneumoniae antigen, and examining the antigen for the presence of bound antibody. In a specific embodiment, the method includes a polypeptide antigen attached to a solid support, and serum is reacted with the support. Subsequently, the support is reacted with a reporter-labeled anti-human antibody. The support is then examined for the presence of reporter-labeled antibody.

[0139] The solid surface reagent employed in the above assays and kits is prepared by known techniques for attaching protein material to solid support material, such as polymeric beads, dip sticks, 96-well plates or filter material. These attachment methods generally include non-specific adsorption of the protein to the support or covalent attachment of the protein, typically through a free amine group, to a chemically reactive group on the solid support, such as an activated carboxyl, hydroxyl, or aldehyde group. Alternatively, streptavidin coated plates can be used in conjunction with biotinylated antigen(s).

Therapeutics and Modes of Administration

[0140] The present invention also provides vaccines comprising one or more polypeptides of the present invention. Heterogeneity in the composition of a vaccine may be provided by combining S. pneumoniae polypeptides of the present invention. Multi-component vaccines of this type are desirable because they are likely to be more effective in eliciting protective immune responses against multiple species and strains of the Streptococcus genus than single polypeptide vaccines. Thus, as discussed in detail below, a multi-component vaccine of the present invention may contain one or more, preferably 2 to about 20, more preferably 2 to about 15, and most preferably 3 to about 8, of the S. pneumoniae polypeptides identified in Table 1, or fragments thereof.

[0141] Multi-component vaccines are known in the art to elicit antibody production to numerous immunogenic components. Decker, M. and Edwards, K., J. Infect. Dis. 174:S270-275 (1996). In addition, a hepatitis B, diphtheria, tetanus, pertussis tetravalent vaccine has recently been demonstrated to elicit protective levels of antibodies in human infants against all four pathogenic agents. Aristegui, J. et al., Vaccine 15:7-9 (1997).

[0142] The present invention thus also includes multi-component vaccines. These vaccines comprise more than one polypeptide, immunogen or antigen. An example of such a multi-component vaccine would be a vaccine comprising more than one of the S. pneumoniae polypeptides described in Table 1. A second example is a vaccine comprising one or more, for example 2 to 10, of the S. pneumoniae polypeptides identified in Table 1 and one or more, for example 2 to 10, additional polypeptides of either streptococcal or non-streptococcal origin. Thus, a multi-component vaccine which confers protective immunity to both a Streptococcal infection and infection by another pathogenic agent is also within the scope of the invention.

[0143] As indicated above, the vaccines of the present invention are expected to elicit a protective immune response against infections caused by species and strains of Streptococcus other than strain of S. pneumoniae deposited with that ATCC.TM..

[0144] Further within the scope of the invention are whole cell and whole viral vaccines. Such vaccines may be produced recombinantly and involve the expression of one or more of the S. pneumoniae polypeptides described in Table 1. For example, the S. pneumoniae polypeptides of the present invention may be either secreted or localized intracellular, on the cell surface, or in the periplasmic space. Further, when a recombinant virus is used, the S. pneumoniae polypeptides of the present invention may, for example, be localized in the viral envelope, on the surface of the capsid, or internally within the capsid. Whole cells vaccines which employ cells expressing heterologous proteins are known in the art. See, e.g., Robinson, K. et al., Nature Biotech. 15:653-657 (1997); Sirard, J. et al., Infect. Immun. 65:2029-2033 (1997); Chabalgoity, J. et al., Infect. Immun. 65:2402-2412 (1997). These cells may be administered live or may be killed prior to administration. Chabalgoity, J. et al., supra, for example, report the successful use in mice of a live attenuated Salmonella vaccine strain which expresses a portion of a platyhelminth fatty acid-binding protein as a fusion protein on its cells surface.

[0145] A multi-component vaccine can also be prepared using techniques known in the art by combining one or more S. pneumoniae polypeptides of the present invention, or fragments thereof, with additional non-streptococcal components (e.g., diphtheria toxin or tetanus toxin, and/or other compounds known to elicit an immune response). Such vaccines are useful for eliciting protective immune responses to both members of the Streptococcus genus and non-streptococcal pathogenic agents.

[0146] The vaccines of the present invention also include DNA vaccines. DNA vaccines are currently being developed for a number of infectious diseases. Boyer, J et al., Nat. Med. 3:526-532 (1997); reviewed in Spier, R., Vaccine 14:1285-1288 (1996). Such DNA vaccines contain a nucleotide sequence encoding one or more S. pneumoniae polypeptides of the present invention oriented in a manner that allows for expression of the subject polypeptide. The direct administration of plasmid DNA encoding B. burgdorferi OspA has been shown to elicit protective immunity in mice against borrelial challenge. Luke, C. et al., J. Infect. Dis. 175:91-97 (1997).

[0147] The present invention also relates to the administration of a vaccine which is co-administered with a molecule capable of modulating immune responses. Kim, J. et al., Nature Biotech. 15:641-646 (1997), for example, report the enhancement of immune responses produced by DNA immunizations when DNA sequences encoding molecules which stimulate the immune response are co-administered. In a similar fashion, the vaccines of the present invention may be co-administered with either nucleic acids encoding immune modulators or the immune modulators themselves. These immune modulators include granulocyte macrophage colony stimulating factor (GM-CSF) and CD86.

[0148] The vaccines of the present invention may be used to confer resistance to streptococcal infection by either passive or active immunization. When the vaccines of the present invention are used to confer resistance to streptococcal infection through active immunization, a vaccine of the present invention is administered to an animal to elicit a protective immune response which either prevents or attenuates a streptococcal infection. When the vaccines of the present invention are used to confer resistance to streptococcal infection through passive immunization, the vaccine is provided to a host animal (e.g., human, dog, or mouse), and the antisera elicited by this antisera is recovered and directly provided to a recipient suspected of having an infection caused by a member of the Streptococcus genus.

[0149] The ability to label antibodies, or fragments of antibodies, with toxin molecules provides an additional method for treating streptococcal infections when passive immunization is conducted. In this embodiment, antibodies, or fragments of antibodies, capable of recognizing the S. pneumoniae polypeptides disclosed herein, or fragments thereof, as well as other Streptococcus proteins, are labeled with toxin molecules prior to their administration to the patient. When such toxin derivatized antibodies bind to Streptococcus cells, toxin moieties will be localized to these cells and will cause their death.

[0150] The present invention thus concerns and provides a means for preventing or attenuating a streptococcal infection resulting from organisms which have antigens that are recognized and bound by antisera produced in response to the polypeptides of the present invention. As used herein, a vaccine is said to prevent or attenuate a disease if its administration to an animal results either in the total or partial attenuation (i.e., suppression) of a symptom or condition of the disease, or in the total or partial immunity of the animal to the disease.

[0151] The administration of the vaccine (or the antisera which it elicits) may be for either a "prophylactic" or "therapeutic" purpose. When provided prophylactically, the compound(s) are provided in advance of any symptoms of streptococcal infection. The prophylactic administration of the compound(s) serves to prevent or attenuate any subsequent infection. When provided therapeutically, the compound(s) is provided upon or after the detection of symptoms which indicate that an animal may be infected with a member of the Streptococcus genus. The therapeutic administration of the compound(s) serves to attenuate any actual infection. Thus, the S. pneumoniae polypeptides, and fragments thereof, of the present invention may be provided either prior to the onset of infection (so as to prevent or attenuate an anticipated infection) or after the initiation of an actual infection.

[0152] The polypeptides of the invention, whether encoding a portion of a native protein or a functional derivative thereof, may be administered in pure form or may be coupled to a macromolecular carrier. Example of such carriers are proteins and carbohydrates. Suitable proteins which may act as macromolecular carrier for enhancing the immunogenicity of the polypeptides of the present invention include keyhole limpet hemacyanin (KLH) tetanus toxoid, pertussis toxin, bovine serum albumin, and ovalbumin. Methods for coupling the polypeptides of the present invention to such macromolecular carriers are disclosed in Harlow et al., Antibodies: A Laboratory Manual, 2nd Ed.; Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1988), the entire disclosure of which is incorporated by reference herein.

[0153] A composition is said to be "pharmacologically acceptable" if its administration can be tolerated by a recipient animal and is otherwise suitable for administration to that animal. Such an agent is said to be administered in a "therapeutically effective amount" if the amount administered is physiologically significant. An agent is physiologically significant if its presence results in a detectable change in the physiology of a recipient patient.

[0154] While in all instances the vaccine of the present invention is administered as a pharmacologically acceptable compound, one skilled in the art would recognize that the composition of a pharmacologically acceptable compound varies with the animal to which it is administered. For example, a vaccine intended for human use will generally not be co-administered with Freund's adjuvant. Further, the level of purity of the S. pneumoniae polypeptides of the present invention will normally be higher when administered to a human than when administered to a non-human animal.

[0155] As would be understood by one of ordinary skill in the art, when the vaccine of the present invention is provided to an animal, it may be in a composition which may contain salts, buffers, adjuvants, or other substances which are desirable for improving the efficacy of the composition. Adjuvants are substances that can be used to specifically augment a specific immune response. These substances generally perform two functions: (1) they protect the antigen(s) from being rapidly catabolized after administration and (2) they nonspecifically stimulate immune responses.

[0156] Normally, the adjuvant and the composition are mixed prior to presentation to the immune system, or presented separately, but into the same site of the animal being immunized. Adjuvants can be loosely divided into several groups based upon their composition. These groups include oil adjuvants (for example, Freund's complete and incomplete), mineral salts (for example, AlK(SO.sub.4).sub.2, AlNa(SO.sub.4).sub.2, AlNH.sub.4(SO.sub.4), silica, kaolin, and carbon), polynucleotides (for example, poly IC and poly AU acids), and certain natural substances (for example, wax D from Mycobacterium tuberculosis, as well as substances found in Corynebacterium parvum, or Bordetella pertussis, and members of the genus Brucella. Other substances useful as adjuvants are the saponins such as, for example, Quil A. (Superfos A/S, Denmark). Preferred adjuvants for use in the present invention include aluminum salts, such as AlK(SO.sub.4).sub.2, AlNa(SO.sub.4).sub.2, and AlNH.sub.4(SO.sub.4). Examples of materials suitable for use in vaccine compositions are provided in Remington's Pharmaceutical Sciences (Osol, A, Ed, Mack Publishing Co, Easton, Pa., pp. 1324-1341 (1980), which reference is incorporated herein by reference).

[0157] The therapeutic compositions of the present invention can be administered parenterally by injection, rapid infusion, nasopharyngeal absorption (intranasopharangeally), dermoabsorption, or orally. The compositions may alternatively be administered intramuscularly, or intravenously. Compositions for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Carriers or occlusive dressings can be used to increase skin permeability and enhance antigen absorption. Liquid dosage forms for oral administration may generally comprise a liposome solution containing the liquid dosage form. Suitable forms for suspending liposomes include emulsions, suspensions, solutions, syrups, and elixirs containing inert diluents commonly used in the art, such as purified water. Besides the inert diluents, such compositions can also include adjuvants, wetting agents, emulsifying and suspending agents, or sweetening, flavoring, or perfuming agents.

[0158] Therapeutic compositions of the present invention can also be administered in encapsulated form. For example, intranasal immunization of mice against Bordetella pertussis infection using vaccines encapsulated in biodegradable microsphere composed of poly(DL-lactide-co-glycolide) has been shown to stimulate protective immune responses. Shahin, R. et al., Infect. Immun. 63:1195-1200 (1995). Similarly, orally administered encapsulated Salmonella typhimurium antigens have also been shown to elicit protective immunity in mice. Allaoui-Attarki, K. et al., Infect. Immun. 65:853-857 (1997). Encapsulated vaccines of the present invention can be administered by a variety of routes including those involving contacting the vaccine with mucous membranes (e.g., intranasally, intracolonicly, intraduodenally).

[0159] Many different techniques exist for the timing of the immunizations when a multiple administration regimen is utilized. It is possible to use the compositions of the invention more than once to increase the levels and diversities of expression of the immunoglobulin repertoire expressed by the immunized animal. Typically, if multiple immunizations are given, they will be given one to two months apart.

[0160] According to the present invention, an "effective amount" of a therapeutic composition is one which is sufficient to achieve a desired biological effect. Generally, the dosage needed to provide an effective amount of the composition will vary depending upon such factors as the animal's or human's age, condition, sex, and extent of disease, if any, and other variables which can be adjusted by one of ordinary skill in the art.

[0161] The antigenic preparations of the invention can be administered by either single or multiple dosages of an effective amount. Effective amounts of the compositions of the invention can vary from 0.01-1,000 .mu.g/ml per dose, more preferably 0.1-500 .mu.g/ml per dose, and most preferably 10-300 .mu.g/ml per dose.

[0162] Having now generally described the invention, the same will be more readily understood through reference to the following example which is provided by way of illustration, and is not intended to be limiting of the present invention, unless specified.

EXAMPLES

Example 1

Expression and Purification of S. Pneumoniae Polypeptides in E. Coli

[0163] The bacterial expression vector pQE10 (QIAGEN, Inc., 9259 Eton Avenue, Chatsworth, Calif., 91311) is used in this example for cloning of the nucleotide sequences shown in Table 1 and for expressing the polypeptides identified in Table 1. The components of the pQE10 plasmid are arranged such that the inserted DNA sequence encoding a polypeptide of the present invention expresses the polypeptide with the six His residues (i.e., a "6.times.His tag")) covalently linked to the amino terminus.

[0164] The DNA sequences encoding the desired portions of the polypeptides of Table 1 are amplified using PCR oligonucleotide primers from either a DNA library constructed from S. pneumoniae, such as the one deposited by the inventors at the ATCC.TM. for convenience, ATCC.TM. Deposit No. 97755, or from DNA isolated from the same organism such as the S. pneumoniae strain deposited with the ATCC.TM. as Deposit No. 55840. A list of PCR primers which can be used for this purpose is provided in Table 3, below. The PCR primers anneal to the nucleotide sequences encoding both the amino terminal and carboxy terminal amino acid sequences of the desired portion of the polypeptides of Table 1. Additional nucleotides containing restriction sites to facilitate cloning in the pQE10 vector were added to the 5' and 3' primer sequences, respectively. Such restriction sites are listed in Table 3 for each primer. In each case, the primer comprises, from the 5' end, 4 random nucleotides to prevent "breathing" during the annealing process, a restriction site (shown in Table 3), and approximately 15 nucleotides of S. pneumoniae ORF sequence (the complete sequence of each cloning primer is shown as SEQ ID NO:227 through SEQ ID NO:452).

[0165] For cloning the polypeptides of Table 1, the 5' and 3' primers were selected to amplify their respective nucleotide coding sequences. One of ordinary skill in the art would appreciate that the point in the protein coding sequence where the 5' primer begins may be varied to amplify a DNA segment encoding any desired portion of the complete amino acid sequences described in Table 1. Similarly, one of ordinary skill in the art would further appreciate that the point in the protein coding sequence where the 3' primer begins may also be varied to amplify a DNA segment encoding any desired portion of the complete amino acid sequences described in Table 1.

[0166] The amplified DNA fragment and the pQE10 vector are digested with the appropriate restriction enzyme(s) and the digested DNAs are then ligated together. The ligation mixture is transformed into competent E. coli cells using standard procedures such as those described in Sambrook et al., Molecular Cloning: a Laboratory Manual, 2nd Ed.; Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989). Transformants are identified by their ability to grow under selective pressure on LB plates. Plasmid DNA is isolated from resistant colonies and the identity of the cloned DNA confirmed by restriction analysis, PCR and DNA sequencing.

[0167] Clones containing the desired constructs are grown overnight ("O/N") in liquid culture under selection. The O/N culture is used to inoculate a large culture, at a dilution of approximately 1:25 to 1:250. The cells are grown to an optical density at 600 nm ("OD600") of between 0.4 and 0.6. Isopropyl-b-D-thiogalactopyranoside ("IPTG") is then added to a final concentration of 1 mM to induce transcription from the lac repressor sensitive promoter, by inactivating the lad repressor. Cells subsequently are incubated further for 3 to 4 hours. Cells are then harvested by centrifugation.

[0168] The cells are stirred for 3-4 hours at 4 C in 6M guanidine-HCl, pH 8. The cell debris is removed by centrifugation, and the supernatant containing the protein of interest is loaded onto a nickel-nitrilo-tri-acetic acid ("NiNTA") affinity resin column (available from QIAGEN, Inc., supra). Proteins with a 6.times.His tag bind to the NI-NTA resin with high affinity and can be purified in a simple one-step procedure (for details see: The QIAexpressionist, 1995, QIAGEN, Inc., supra). Briefly, the supernatant is loaded onto the column in 6 M guanidine-HCl, pH8, the column is first washed with 10 volumes of 6 M guanidine-HCl, pH8, then washed with 10 volumes of 6 M guanidine-HCl pH6, and finally the polypeptide is eluted with 6 M guanidine-HCl, pH 5.0.

[0169] The purified protein is then renatured by dialyzing it against phosphatebuffered saline (PBS) or 50 mM Na-acetate, pH 6 buffer plus 200 mM NaCl. Alternatively, the protein can be successfully refolded while immobilized on the Ni-NTA column. The recommended conditions are as follows: renature using a linear 6M-1M urea gradient in 500 mM NaCl, 20% glycerol, 20 mM Tris/HCl pH7.4, containing protease inhibitors. The renaturation should be performed over a period of 1.5 hours or more. After renaturation the proteins can be eluted by the addition of 250 mM imidazole. Imidazole is removed by a final dialyzing step against PBS or 50 mM sodium acetate pH6 buffer plus 200 mM NaCl. The purified protein is stored at 4.degree. C. or frozen at -80.degree. C.

[0170] The DNA sequences encoding the amino acid sequences of Table 1 may also be cloned and expressed as fusion proteins by a protocol similar to that described directly above, wherein the pET-32b(+) vector (Novagen, 601 Science Drive, Madison, Wis. 53711) is preferentially used in place of pQE10.

[0171] Each of the polynucleotides shown in Table 1, was successfully amplified and subcloned into pQE10 as described above using the PCR primers shown in Table 3. These pQE10 plasmids containing the DNAs of Table 1, except SP023, SP042, SP054, SP063, SP081, SP092, SP114, SP122, SP123, SP126, and SP127, were deposited with the ATCC.TM. as a pooled deposit as a convenience to those of skill in the art. This pooled deposit was deposited on Oct. 16, 1997 and given ATCC.TM. Deposit No. 209369. Those of ordinary skill in the art appreciate that isolating an individual plasmid from the pooled deposit is trivial provided the information and reagents described herein. Each of the deposited clones is capable of expressing its encoded S. pneumoniae polypeptide.

Example 2

Immunization and Detection of Immune Responses

Methods

[0172] Growth of Bacterial Innoculum, Immunization of Mice and Challenge with S. Pneumoniae.

[0173] Propagation and storage of, and challenge by S. pneumoniae are preformed essentially as described in Aaberge, I. S. et al., Virulence of Streptococcus pneumoniae in mice: a standardized method for preparation and frozen storage of the experimental bacterial inoculum, Microbial Pathogenesis, 18:141 (1995), incorporated herein by reference.

[0174] Briefly, Todd Hewitt (TH) broth (Difco laboratories, Detroit, Mich.) with 17% FCS, and horse blood agar plates are used for culturing the bacteria. Both broth and blood plates are incubated at 37.degree. C. in a 5% CO.sub.2 atmosphere. Blood plates are incubated for 18 hr. The culture broth is regularly 10-fold serially diluted in TH broth kept at room temperature and bacterial suspensions are kept at room temperature until challenge of mice.

[0175] For active immunizations C3H/HeJ mice (The Jackson Laboratory, Bar Harbor, Me.) are injected intraperitoneally (i.p.) at week 0 with 20 g of recombinant streptococcal protein, or phosphate-buffered saline (PBS), emulsified with complete Freund's adjuvant (CFA), given a similar booster immunization in incomplete Freund's adjuvant (IFA) at week 4, and challenged at week 6. For challenge S. pneumoniae are diluted in TH broth from exponentially-growing cultures and mice are injected subcutaneously (s.c.) at the base of the tail with 0.1 ml of these dilutions (serial dilutions are used to find medium infectious dose). Streptococci used for challenge are passaged fewer than six times in vitro. To assess infection, blood samples are obtained from the distal part of the lateral femoral vein into heparinized capillary tubes. A 25 ul blood sample is serially 10-fold diluted in TH broth, and 25 ul of diluted and undiluted blood is plated onto blood agar plates. The plates are incubated for 18 hr. and colonies are counted.

[0176] Other methods are known in the art, for example, see Langermann, S. et al., J. Exp. Med., 180:2277 (1994), incorporated herein by reference.

Immunoassays

[0177] Several immunoassay formats are used to quantify levels of streptococcal-specific antibodies (ELISA and immunoblot), and to evaluate the functional properties of these antibodies (growth inhibition assay). The ELISA and immunoblot assays are also used to detect and quantify antibodies elicited in response to streptococcal infection that react with specific streptococcal antigens. Where antibodies to certain streptococcal antigens are elicited by infection this is taken as evidence that the streptococcal proteins in question are expressed in vivo. Absence of infection-derived antibodies (seroconversion) following streptococcal challenge is evidence that infection is prevented or suppressed. The immunoblot assay is also used to ascertain whether antibodies raised against recombinant streptococcal antigens recognize a protein of similar size in extracts of whole streptococci. Where the natural protein is of similar, or identical, size in the immunoblot assay to the recombinant version of the same protein, this is taken as evidence that the recombinant protein is the product of a full-length clone of the respective gene.

Enzyme-Linked Immunosorbant Assay (ELISA).

[0178] The ELISA is used to quantify levels of antibodies reactive with streptococcus antigens elicited in response to immunization with these streptococcal antigens. Wells of 96 well microtiter plates (Immunlon 4, Dynatech, Chantilly, Va., or equivalent) are coated with antigen by incubating 50 1 of 1 g/ml protein antigen solution in a suitable buffer, typically 0.1 M sodium carbonate buffer at pH 9.6. After decanting unbound antigen, additional binding sites are blocked by incubating 100 1 of 3% nonfat milk in wash buffer (PBS, 0.2% Tween 20, pH 7.4). After washing, duplicate serial two-fold dilutions of sera in PBS, Tween 20, 1% fetal bovine serum, are incubated for 1 hr, removed, wells are washed three times, and incubated with horseradish peroxidase-conjugated goat anti-mouse IgG. After three washes, bound antibodies are detected with H.sub.2O.sub.2 and 2,2'-azino-di-(3-ethylbenzthiazoline sulfonate) (Schwan, T. G., et al., Proc. Natl. Acad. Sci. USA 92:2909-2913 (1985)) (ABTS.RTM., Kirkegaard & Perry Labs., Gaithersburg, Md.) and A.sub.405 is quantified with a Molecular Devices, Corp. (Menlo Park, Calif.) Vmax.TM. plate reader. IgG levels twice the background level in serum from naive mice are assigned the minimum titer of 1:100.

Sodiumdodecylsulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) and Immunoblotting

[0179] Using a single well format, total streptococcal protein extracts or recombinant streptococcal antigen are boiled in SDS/2-ME sample buffer before electrophoresis through 3% acrylamide stacking gels, and resolving gels of higher acrylamide concentration, typically 10-15% acrylamide monomer. Gels are electro-blotted to nitrocellulose membranes and lanes are probed with dilutions of antibody to be tested for reactivity with specific streptococcal antigens, followed by the appropriate secondary antibody-enzyme (horseradish peroxidase) conjugate. When it is desirable to confirm that the protein had transferred following electro-blotting, membranes are stained with Ponceau S. Immunoblot signals from bound antibodies are detected on x-ray film as chemiluminescence using ECL.TM. reagents (Amersham Corp., Arlington Heights, Ill.).

Example 3

Detection of Streptococcus mRNA Expression

[0180] Northern blot analysis is carried out using methods described by, among others, Sambrook et al., supra. to detect the expression of the S. pneumoniae nucleotide sequences of the present invention in animal tissues. A cDNA probe containing an entire nucleotide sequence shown in Table 1 is labeled with .sup.32P using the Rediprime.TM. DNA labeling system (Amersham Life Science), according to manufacturer's instructions. After labeling, the probe is purified using a CHROMA SPIN-100.TM. column (Clontech Laboratories, Inc.), according to manufacturer's protocol number PT1200-1. The purified labeled probe is then used to detect the expression of Streptococcus mRNA in an animal tissue sample.

[0181] Animal tissues, such as blood or spinal fluid, are examined with the labeled probe using ExpressHyb.TM. hybridization solution (Clontech) according to manufacturer's protocol number PT1190-1. Following hybridization and washing, the blots are mounted and exposed to film at -70 C overnight, and films developed according to standard procedures.

[0182] It will be clear that the invention may be practiced otherwise than as particularly described in the foregoing description and examples.

[0183] Numerous modifications and variations of the present invention are possible in light of the above teachings and, therefore, are within the scope of the appended claims.

[0184] The entire disclosure of all publications (including patents, patent applications, journal articles, laboratory manuals, books, or other documents) cited herein are hereby incorporated by reference.

TABLE-US-00001 TABLE 1 Description SEQ ID NO: SP001 nucleotide 1 SP001 AMINO ACID 2 SP004 nucleotide 3 SP004 amino acid 4 SP006 nucleotide 5 SP006 amino acid 6 SP007 nucleotide 7 SP007 amino acid 8 SP008 nucleotide 9 SP008 amino acid 10 SP009 nucleotide 11 SP009 amino acid 12 SP010 nucleotide 13 SP010 amino acid 14 SP011 nucleotide 15 SP011 amino acid 16 SP012 nucleotide 17 SP012 nucleotide 18 SP013 nucleotide 19 SP013 amino acid 20 SP014 nucleotide 21 SP014 amino acid 22 SP015 nucleotide 23 SP015 amino acid 24 SP016 nucleotide 25 SP016 amino acid 26 SP017 nucleotide 27 SP017 amino acid 28 SP019 nucleotide 29 SP019 amino acid 30 SP020 nucleotide 31 SP020 amino acid 32 SP021 nucleotide 33 SP021 amino acid 34 SP022 nucleotide 35 SP022 amino acid 36 SP023 nucleotide 37 SP023 amino acid 38 SP025 nucleotide 39 SP025 amino acid 40 SP028 nucleotide 41 SP028 amino acid 42 SP030 nucleotide 43 SP030 amino acid 44 SP031 nucleotide 45 SP031 amino acid 46 SP032 nucleotide 47 SP032 amino acid 48 SP033 nucleotide 49 SP033 amino acid 50 SP034 nucleotide 51 SP034 amino acid 52 SP035 nucleotide 53 SP035 amino acid 54 SP036 nucleotide 55 SP036 amino acid 56 SP038 nucleotide 57 SP038 amino acid 58 SP039 nucleotide 59 SP039 amino acid 60 SP040 nucleotide 61 SP040 amino acid 62 SP041 nucleotide 63 SP041 amino acid 64 SP042 nucleotide 65 SP042 amino acid 66 SP043 nucleotide 67 SP043 amino acid 68 SP044 nucleotide 69 SP044 amino acid 70 SP045 nucleotide 71 SP045 nucleotide 72 SP046 nucleotide 73 SP046 amino acid 74 SP048 nucleotide 75 SP048 amino acid 76 SP049 nucleotide 77 SP049 amino acid 78 SP050 nucleotide 79 SP050 amino acid 80 SP051 nucleotide 81 SP051 amino acid 82 SP052 nucleotide 83 SP052 amino acid 84 SP053 nucleotide 85 SP053 amino acid 86 SP054 nucleotide 87 SP054 amino acid 88 SP055 nucleotide 89 SP055 amino acid 90 SP056 nucleotide 91 SP056 amino acid 92 SP057 nucleotide 93 SP057 amino acid 94 SP058 nucleotide 95 SP058 amino acid 96 SP059 nucleotide 97 SP059 amino acid 98 SP060 nucleotide 99 SP060 amino acid 100 SP062 nucleotide 101 SP062 amino acid 102 SP063 nucleotide 103 SP063 amino acid 104 SP064 nucleotide 105 SP064 amino acid 106 SP065 nucleotide 107 SP065 amino acid 108 SP067 nucleotide 109 SP067 amino acid 110 SP068 nucleotide 111 SP068 amino acid 112 SP069 nucleotide 113 SP069 amino acid 114 SP070 nucleotide 115 SP070 amino acid 116 SP071 nucleotide 117 SP071 amino acid 118 SP072 nucleotide 119 SP072 amino acid 120 SP073 nucleotide 121 SP073 amino acid 122 SP074 nucleotide 123 SP074 amino acid 124 SP075 nucleotide 125 SP075 amino acid 126 SP076 nucleotide 127 SP076 amino acid 128 SP077 nucleotide 129 SP077 amino acid 130 SP078 nucleotide 131 SP078 amino acid 132 SP079 nucleotide 133 SP079 amino acid 134 SP080 nucleotide 135 SP080 amino acid 136 SP081 nucleotide 137 SP081 amino acid 138 SP082 nucleotide 139 SP082 amino acid 140 SP083 nucleotide 141 SP083 amino acid 142 SP084 nucleotide 143 SP084 amino acid 144 SP085 nucleotide 145 SP085 amino acid 146 SP086 nucleotide 147 SP086 amino acid 148 SP087 nucleotide 149 SP087 amino acid 150 SP088 nucleotide 151 SP088 amino acid 152 SP089 nucleotide 153 SP089 amino acid 154 SP090 nucleotide 155 SP090 amino acid 156 SP091 nucleotide 157 SP091 amino acid 158 SP092 nucleotide 159 SP092 amino acid 160 SP093 nucleotide 161 SPO93 amino acid 162 SP094 nucleotide 163 SP094 amino acid 164 SP095 nucleotide 165 SP095 amino acid 166 SP096 nucleotide 167 SP096 amino acid 168 SP097 nucleotide 169 SP097 amino acid 170 SP098 nucleotide 171 SP098 amino acid 172 SP099 nucleotide 173 SP099 amino acid 174 SP100 nucleotide 175 SP100 amino acid 176 SP101 nucleotide 177 SP101 amino acid 178 SP102 nucleotide 179 SP102 amino acid 180 SP103 nucleotide 181 SP103 amino acid 182 SP105 nucleotide 183 SP105 amino acid 184 SP106 nucleotide 185 SP106 amino acid 186 SP107 nucleotide 187 SP107 amino acid 188 SP108 nucleotide 189 SP108 amino acid 190 SP109 nucleotide 191 SP109 amino acid 192 SP110 nucleotide 193 SP110 amino acid 194 SP111 nucleotide 195 SP111 amino acid 196 SP0112 nucleotide 197 SP0112 amino acid 198 SP113 nucleotide 199 SP113 amino acid 200 SP114 nucleotide 201 SP114 amino acid 202 SP115 nucleotide 203 SP115 amino acid 204 SP117 nucleotide 205 SP117 amino acid 206 SP118 nucleotide 207 SP118 amino acid 208 SP119 nucleotide 209 SP119 amino acid 210 SP120 nucleotide 211 SP120 amino acid 212 SP121 nucleotide 213 SP121 amino acid 214 SP122 nucleotide 215 SP122 amino acid 216 SP123 nucleotide 217 SP123 amino acid 218 SP124 amino acid 219 SP124 amino acid 220 SP125 nucleotide 221 SP125 amino acid 222 SP126 nucleotide 223 SP126 amino acid 224 SP127 nucleotide 225 SP127 amino acid 226

TABLE-US-00002 TABLE 2 S. pneumoniae Antigenic Epitopes SP001 Lys-1 to Ile-10; Leu-13 to Lys-32; Arg-41 to Ile-51; Ser-85 to Glu-97; Ala-159 to His-168; Val-309 to Thr-318; Val-341 to Asn-352; Asn-415 to Met-430; Phe-454 to Asn-464; Ser-573 to Gly-591; Asn-597 to Thr-641; and Asn-644 to Ala-664. SP004 Thr-9 to Thr-24; Ile-29 to Ala-48; Thr-49 to Val-56; Val-286 to Val-312; Pro-316 to Glu-344; Val-345 to Ile-367; Gln-368 to Val-399; Ser-400 to Glu-431; Asn-436 to Ala- 457; Ile-467 to Ala-498; and Thr-499 to Glu-540. SP006 Glu-1 to Lys-13; Pro-24 to Gly-36; Val-104 to Thr-112; Ala-118 to Asn-130; Trp-137 to Ala-146; Ser-151 to Ile-159; Ile-181 to Leu-188; and Pro-194 to Tyr-202. SP007 Gly-1 to Asn-7; Tyr-24 to Gln-34; His-47 to Phe-55; Ser-60 to Ala-67; Ala-122 to Leu-129; Leu- 221 to Lys-230; Val-236 to Phe-256; and Asp-271 to Gly-283; and Leu-291 to Asp-297. SP008 Leu-4 to Lys-17; Gln-24 to Leu-32; Asp-60 to Ser-66; Ser-70 to Asp-76; Ala-276 to Lys-283; Asn- 304 to Lys-311; and Thr-429 to Pro-437. SP009 Thr-4 to Glu-11; Leu-50 to Asp-60; Ile-102 to Trp-123; and Ser-138 to Ile-157. SP010 Phe-34 to Gly-41; Asp-44 to Lys-50; Leu-172 to Val-186; Leu-191 to Val-198; Ser-202 to Ile-209; and Val-213 to Leu-221. SP011 Asn-2 to Thr-10; Asp-87 to Ala-102; Tyr-125 to Glu-132; Thr-181 to Tyr-189; Arg-217 to Thr-232; Asn-257 to Lys-264; Pro-271 to Ser-278; Tyr-317 to Ala-325; Glu-327 to Pro-337; and Thr-374 to Val-381. SP012 Gly-1 to Lys-19; Phe-34 to Tyr-41; Leu-109 to Lys-126; and Leu-231 to Glu-247. SP013 Ala-1 to Lys-12; Ile-42 to Pro-53; Leu-138 to Lys-146; Ile-205 to Lys-217; Ser-235 to Ile-251; and Ser-261 to Tyr-272. SP014 Gly-1 to Val-16; Leu-35 to Leu-44; Asp-73 to Asp-81; Ile-83 to Asp-92; Glu-145 to Ile-153; Phe- 188 to Asn-196; Ser-208 to Phe-215; Ile-224 to Leu-231; and Asn-235 to Ala-243. SP015 Ser-1 to Pro-16; Asn-78 to Glu-88; Ala-100 to Val-108; Ala-122 to Thr-129; Thr-131 to Ser-137; Leu-201 to Ser-220; and Gly-242 to Val-251. SP016 Gly-1 to Glu-20; Thr-30 to Val-38; Gln-94 to Asn-105; Lys-173 to Pro-182; Gly-189 to Arg-197; Ser-207 to Val-224; Pro-288 to Leu-298; Ala-327 to Ala-342; and Ser-391 to Ala-402. SP017 Ser-1 to Thr-12; Ala-36 to Tyr-45; Gln-48 to Ile-54; Lys-59 to Lys-76; Tyr-113 to Leu-138; and Phe-212 to Asp-219. SP019 Val-97 to Glu-117; Asp-163 to Leu-169; Thr-182 to Thr-191; and Lys-241 to Ser-250. SP020 Asn-18 to Lys-25; Thr-47 to Glu-60; Trp-75 to Val-84; Gly-102 to Val-110; Pro-122 to Ala-131; and Glu-250 to Pro-258. SP021 Ser1 to Asp-8; Val-44 to Asp-54; Ala-117 to Val-125; Thr-165 to Thr-173; and Glu-180 to Pro-189. SP022 Phe-5 to Lys-13; Thr-20 to Ser-36; Glu-59 to Lys-81; Tyr-85 to Gly-93; Trp-94 to Trp-101; and Thr-195 to Trp-208. SP023 Gln-45 to Glu-59; Asp-69 to Pro-85; Lys-111 to Asn-121; Pro-218 to Ala-228; and Glu-250 to Asn- 281. SP025 Gln-14 to Thr-20; Gly-27 to Phe-33; Gly-63 to Glu-71; and Ile-93 to Phe-102. SP028 Asp-171 to Pro-179; Tyr-340 to Glu-350; Pro-455 to Tyr-463; and Asp-474 to Pro-480. SP030 Leu-22 to Leu-37; Trp-81 to Ala-90; Phe-101 to Ala-106; Thr-124 to Tyr-130; and Asn-138 to Glu- 144. SP031 Asp-8 to Val-16; Gly-27 to Thr-35; Gly-178 to Asp-195; Thr-200 to Asp209; Trp-218 to Leu-224; and Lys-226 to Asp-241. SP032 Ser-9 to Asp-28; Phe-31 to Val-40; Gly-42 to Arg-50; Ile-52 to Leu-60; Asp-174 to Phe-186; Leu- 324 to Met-333; and Thr-340 to Asn-347. SP033 Gln-2 to Ile-13; Phe-46 to Ile-53; and Asp-104 to Thr-121. SP034 Glu-36 to Gly-43; Ala-188 to Asp-196; Trp-313 to Gly-320; and Leu-323 to Leu-329. SP035 Arg-19 to Asp-36; Asp-47 to Val-57; Asn-134 to Thr-143; Asp-187 to Arg-196; and Glu-222 to Ser-230. SP036 Arg-10 to Arg-17; Lys-29 to Ser-39; Ser-140 to Ala-153; Arg-158 to Tyr-169; Asp-175 to Ala-183; Gly-216 to Asn-236; Ala-261 to Leu-270; Arg-282 to Phe-291; and Thr-297 to Ala-305; Pro-342 to Gln-362; Phe-455 to Asp-463; His-497 to Thr-511; Ala-521 to Gly-529; Ile-537 to Val-546; Ile-556 to Ala-568; Pro-581 to Ser-595; Glu-670 to Ala-685; Ser-696 to Ala-705 and Leu-782 to Ser-791. SP038 Glu-61 to Pro-69; Phe-107 to Ala-115; Leu-130 to Tyr-141; Ala-229 to Glu-237; Ser-282 to Asn- 287; Ala-330 to Glu-338; and Tyr-387 to Glu-393. SP039 Ser-28 to Asp-35; Pro-88 to Pro-96; Leu-125 to Arg-135; Phe-149 to Leu-157; Gln-246 to Val-254; Ala-357 to Thr-362; Gly-402 to Lys-411; and Leu-440 to Pro-448. SP040 Thr-21 to Ile-30; His-54 to Gln-68; Arg-103 to Leu-117; and Thr-127 to Leu-136. SP041 Gly-36 to Asp-49; Leu-121 to Val-128; and Ala-186 to Ile-196. SP042 Gly-11 to Arg-19; Ile-23 to Lys-31; His-145 to Asn-151; Gln-159 to Asp-166; Ile-175 to Asp-181; Gly-213 to Tyr-225; Ile-283 to Val-291; Pro-329 to Glu-364; Arg-372 to Ser-386; Thr-421 to Phe- 430; Leu-445 to Val-453; Ile-486 to Ala-497; Asp-524 to Ala-535; His-662 to Gly-674; and His- 679 to Gln-702. SP043 Lys-2 to Asp-12; Val-58 to Asn-68; Ser-87 to Asp-95; and Asp-102 to Lys-117. SP044 Gln-3 to Lys-11; Asp-37 to Tyr-52; Glu-171 to Leu-191; His-234 to Asn-247; and Asn-283 to Ala- 291. SP045 Tyr-52 to Ile-63; Asp-212 to Gln-227; Ser-315 to Thr-332; Leu-345 to Phe-354; Asp-362 to Val- 370; Thr-518 to Asn-539; Ala-545 to Lys-559; and Val-601 to Pro-610. SP046 Gln-9 to Ala-18; Glu-179 to Lys-186; Lys-264 to Glu-271; Gly-304 to Glu-17; Ser-503 to Asn-511; Asn-546 to Thr-553; and Asn-584 to Asp-591. SP048 Tyr-4 to Asp-25; Lys-33 to Val-70; Asp-151 to Thr-170; Asp-222 to Val-257; Thr-290 to Phe- 301; and Gly-357 to Val-367. SP049 Ala-23 to Arg-37; Tyr-85 to Gln-95; Glu-106 to Ile-118; Arg-131 to ILE-144; Gly-150 to Ser- 162; and Ala-209 to Asp-218. SP050 Asp-95 to Glu-113; Gly-220 to Gly-228; Asn-284 to Glu-295; Thr-298 to Val-315. SP051 Lys-16 to Glu-50; Lys-57 to Asn-104; Ser-158 to Trp-173; Asp-265 to Pro-279; Val-368 to Tyr-386; Glu-420 to Ile-454; Pro-476 to Ile-516; Phe-561 to Gly-581; Thr-606 to Gly-664; and Glu-676 to Val-696. SP052 Asn-41 to Tyr-60; Phe-80 to Glu-103; Ala-117 to Val-139; Ile-142 to Leu-155; Val-190 to Lys- 212; Glu-276 to Phe-283; Arg-290 to Ser-299; Leu-328 to Val-351; Gly-358 to Thr-388; Glu- 472 to Ala-483; Val-533 to Asn-561; Asp-595 to Val-606; Glu-609 to Val-620; Glu-672 to Ser- 691. SP053 Ala-62 to Val-101; Thr-147 to Leu-174; Lys-204 to Val-216; Gln-228 to Val-262; Ser-277 to Gly-297; Thr-341 to Glyn-368; Thr-385 to Ala-409; Thr-414 to Ser-453; Asn-461 to Leu-490; Glu-576 to Thr-625; Gly-630 to Arg-639; and Asp-720 to Leu-740. SP054 Glu-7 to Val-28; and Tyr-33 to Glu-44. SP055 Pro-3 to Val-18; Thr-21 to Lys-53; Val-84 to Lys-99; Ile-162 to Val-172; and Val-204 to Ser- 241. SP056 Val-34 to Tyr-41; Leu-47 to Glu-55; and Pro-57 to Gln-66. SP057 Asp-1 to Val-25; Pro-29 to Ile-80; Asn-96 to Val-145; and Pro-150 to Glu-172. SP058 Ala-64 to Thr-70; Leu-82 to His-138; and Val-228 to Asn-236. SP059 Val-10 to Thr-24; Ser-76 to Pro-102; Ser-109 to Ile-119; Ser-124 to Val-130; Thr-186 to Ile- 194; and Asn-234 to Ser-243. SP060 Leu-70 to Arg-76; and Val-79 to Ile-88. SP062 Glu-14 to Lys-28; Ser-32 to Lys-46; and Glu-66 to Thr-74. SP063 Ile-10 to Val-25; Val-30 to Thr-40; Asp-44 to Pro-54; Asn-57 to Val-63; Pro-71 to Val-100; and Thr-105 to Thr-116. SP064 Pro-12 to Leu-32; Val-40 to Leu-68; Asp-95 to Ala-125; Ser-164 to Glu-184; Ser-314 to Glu- 346; Asn-382 to Val-393; Leu-463 to Gln-498; Asn-534 to Lys-548; and Lys-557 to Gly-605. SP065 Asn-2 to Ile-12; Ala-39 to Thr-61; and His-135 to Ala-155. SP067 Gly-1 to Thr-13; Asp-203 to Asn-218; and Gly-240 to Asp-253. SP068 Ser-2 to Ser-12; Val-17 to Gln-26; and Lys-54 to Cys-67. SP069 Ser-32 to Thr-41; Pro-66 to Glu-80; Thr-110 to Val-122; and Val-147 to Thr-180. SP070 Lys-6 to Tyr-16; Gln-19 to Ile-27; Arg-50 to Ala-58; Leu-112 to Val-128; Ile-151 to Asn-167; Leu-305 to Phe-321. SP071 Gln-92 to Asn-158; Gln-171 to Gln-188; Val-204 to Val-240; Thr-247 to Ala-273; Glu-279 to Thr-338; Pro-345 to Glu-368; Asn-483 to Lys-539; Val-552 to Ala-568; Glu-575 to Ser-591; Ser-621 to Gly-640; Gln-742 to Gly-758. SP072 Val-68 to Tyr-81; Tyr-86 to Val-121; Leu-127 to Gly-140; Gly-144 to Ala-155; Gln-168 to Val- 185; Asp-210 to Try-241; Glu-246 to Thr-269; Lys-275 to Tyr-295; Gly-303 to Pro-320; Arg- 327 to Ile-335; Thr-338 to Thr-364; Tyr-478 to Phe-495; and Tyr-499 to Arg-521. SP073 Glu-37 to Val-45; Glu-55 to Val-68; Thr-104 to Thr-119; Ile-127 to Tyr-135; Asn-220 to Ile-232; Thr-237 to Ala-250; Ser-253 to Ala-263; Glu-284 to Ile-297; and Met-438 to Asn-455. SP074 Gly-2 to Ala-12; Gly-96 to Ile-110; and Thr-220 to Phe-239.

SP075 Phe-33 to Tyr-42; Gln-93 to Gly-102; and Val-196 to Asp-211. SP076 Ser-64 to Leu-76; and Phe-81 to Ala-101. SP077 Asp-1 to Glu-12; Tyr-26 to Val-36; and Val-51 to Try-62. SP078 Ala-193 to Ile-208; Tyr-266 to Asn-275; Glu-356 to Leu-369; Ala-411 to Gly-422; Ser-437 to Pro-464; Thr-492 to Glu-534; and Glu-571 to Gln-508. SP079 Gly-11 to Leu-20; Lys-39 to Leu-48; Leu-72 to Val-85; Asn-147 to Ser-158; Ile-178 to Asp-187; Tyr-189 to Gln-201; and Leu-203 to Ala-216 SP080 Ser-2 to Glu-12; Gln-42 to Ala-51; Ala-116 to Ser-127; Phe-131 to Asp-143; and Ile-159 to Ile- 171. SP081 Gln-2 to Leu-9; Gln-49 to Cys-57; Ile-108 to Val-131; Gly-134 to Leu-145; and Trp-154 to Cys- 162. SP082 Ile-101 to Ser-187; Gly-191 to Asn-221; Arg-225 to Arg-236; Tyr-239 to Leu-255; and Gly-259 to Arg-268. SP083 Ser-28 to Asp-70. SP084 Leu-42 to Gln-66; Thr-69 to Lys-81; Glu-83 to Arg-92; and Gly-98 to Asn-110. SP085 Gln-2 to Val-22; and Ser-45 to Glu-51. SP086 Leu-18 to Gln-65; and Lys-72 to Val-83. SP087 Ser-45 to Leu-53; and Thr-55 to Gln-63 SP088 Pro-8 to Ile-16; Leu-25 to Trp-33; Tyr-35 to Gln-43; Leu-51 to Val-59; Val-59 to Arg-67; Thr-55 to Tyr-63; Asn-85 to Gly-93; Thr-107 to Leu-115; Leu-115 to Trp-123; Ala-121 to Thr-129; Tyr-153 to Ala-161; His-176 to Gly-184; Tyr-194 to Ala-202; Ala-217 to Gly-225; and Asn-85 to Gly-93. SP089 Trp-43 to Ala-51; Gln-68 to Phe-76; Val-93 to Gln-101; Phe-106 to Phe-114; Lys-117 to Lys-125; Trp-148 to Phe-156; Glu-168 to Gln-176; Ile-193 to Tyr-201; Lys-203 to Lys-211; Glu-212 to Gln-220; Ile-237 to Tyr-245; Lys-247 to Lys-255; Glu-256 to Gln-264; Met-275 to Gly-283; Lys-286 to Gly-294; Trp-292 to Glu-300; Asp-289 to Thr-297; Tyr-315 to Ser-323; Asp-334 to Lys-342; Pro-371 to Arg-379; Arg-485 to Asn-493; Lys-527 to Arg-535; Phe-537 to Met-545; and Tyr-549 to Glu-557. SP090 Phe-2 to Gln-10; Gln-13 to Lys-21; Tyr-19 to Glu-27; Tyr-39 to Met-47; Pro-65 to Leu-73; Tyr-121 to His-129; Lys-147 to Ile-155; Gly-161 to Lys-169; Gly-218 to Trp-226; Asp-230 to Thr-238; Tyr-249 to Ala-257; and Ala-272 to Gly-280. SP091 Ser-19 to Ser-27; Asn-25 to Thr-33; Val-51 to Gln-59; Asn-75 to Asn-83; Ile-103 to Trp-111; Tyr-113 to Ala-121; Leu-175 to Asn-183; Glu-185 to Trp-193; Ala-203 to Tyr-211; Val-250 to Phe-258; Asn-260 to Thr-268; Ser-278 to Asp-286; Tyr-305 to Leu-313; Asn-316 to Gly-324; Asn-374 to Asp-382; Asn-441 to Gly-449; and Ser-454 to Gln-462. SP092 Arg-95 to Glu-103; Ala-216 to Val-224; Leu-338 to Glu-346; Pro-350 to Ala-358; Pro-359 to Ala-367; Pro-368 to Ala-376; Pro-377 to Ala-385; Pro-386 to Ala-394; Pro-395 to Ala-403; Pro-350 to Ala-358; Gln-414 to Lys-422; Pro-421 to Asn-429; Trp-465 to Tyr-473; Phe-487 to Tyr-495; Asn-517 to Gly-525; Trp-586 to Tyr-594; Phe-608 to Tyr-616; and Asp-630 to Gly-638. SP093 Gln-30 to Ile-38; Gln-52 to Val-60; Ala-108 to His-116; Tyr-133 to Glu-141; Tyr-192 to Ala-200; and Phe-207 to Ser-215. SP094 Ala-87 to Val-95; Leu-110 to Cys-118; Gln-133 to Leu-141; Ser-185 to Leu-193; Ile-195 to Gly-203; Asp-206 to Gln-214; Ser-211 to Gly-219; Ile-241 to Thr-249. SP095 Arg-1 to Gln-9; Phe-7 to Asn-15; Thr-21 to Asn-30; Leu-46 to Phe-54; and Ser-72 to Met-80. SP096 Gly-29 to Ile-37; Glu-52 to Ser-60; and Leu-64 to Gly-72. SP097 Ala-11 to Thr-19; Glu-53 to Glu-61; Ser-91 to Lys-99; Thr-123 to Gln-131; and Gly-209 to Lys-217. SP098 Thr-3 to Ser-11; Gly-38 to Phe-46; Tyr-175 to Asn-183; Met-187 to Cys-195; Gln-197 to Leu-205; Tyr-307 to Gln-315; Gly-318 to Tyr-326; Asn-348 to Val-356; Lys-377 to Pro-385; and Leu-415 to Val-423. SP099 Arg-19 to Gly-27; Asp-76 to Ser-84; Val-90 to Lys-98; Phe-165 to Val-173; Leu-237 to Pro-245. SP100 His-111 to Gln-119; Ser-141 to His-149; Asp-154 to Ser-162; Gln-158 to Gln-166; Asp-154 to Gln-166; Lys-180 to Gln-188; and Ser-206 to Gln-214. SP101 Glu-23 to Glu-31; Glu-40 to Val-48; Gln-50 to Ser-58; Thr-61 to Ile-69; Leu-82 to Ile-90; Ala-108 to Leu-116; Gln-121 to Pro-129; and Leu-130 to Thr-138. SP102 Asp-32 to His-40; Arg-48 to Lys-56; and Asp-102 to Thr-110. SP103 Arg-5 to Gln-13; Gln-22 to Leu-30; Arg-151 to Gln-159; Arg-167 to Gln-175; Pro-189 to Glu-197; Gly-207 to Leu-215; Ser-219 to Gln-227; Ser-233 to Ser-241; Pro-255 to Asp-264; Lys-272 to Gly-280; Ser-318 to Val-326; Thr-341 to Asp-351; Asn-356 to Thr-364; Val-370 to Tyr-378; Ile-379 to Gln-387; and Met-435 to Tyr-443. SP105 Asn-28 to Pro-36; Thr-77 to Phe-85; Arg-88 to Val-96; Gly-107 to Phe-115; Asp-169 to Asp-177; His-248 to Ser-256; and Ser-274 to Ala-282. SP106 Val-10 to Thr-18; Ile-62 to Tyr-70; Ile-71 to Pro-79; Lys-86 to Gln-94; Lys-100 to Thr-108; Phe-132 to Leu-140; and Asp-145 to Arg-153. SP107 Asp-33 to Val-41; and Arg-63 to Gln-71. SP108 Lys-9 to Gln-17; Leu-44 to Ser-52; Ser-63 to Phe-71; Tyr-109 to Ser-117; Ile-183 to Ile-191; Pro-194 to Leu-202; Gly-257 to Gln-265; Ala-323 to Thr-331; and Leu-381 to Tyr-389. SP109 Asn-2 to Gln-10; Ala-65 to Lys-73; Leu-76 to Glu-84; Thr-111 to Asp-119; Gln-116 to Tyr-124; Tyr-130 to Val-138; Asp-173 to Gly-181; Asp-196 to Ser-204; Asn-231 to Ser-239; Phe-252 to Ser-260; Phe-270 to Tyr-278; Val-291 to His-299; Asp-306 to Leu-314; and Pro-327 to Gly-335. SP110 Ser-8 to Glu-16; Ile-37 to Val-45; Ala-107 to Val-115; and Gly-122 to Thr-130. SP111 Asp-19 to Glu-28; Leu-43 to Ala-51; Asn-102 to Phe-110; Gln-133 to Ser-141; Phe-162 to Asp-170; Tyr-194 to Met-202; and Asp-273 to Ser-281. SP112 Asp-3 to Gln-11; Gly-21 to Ile-29; Ala-46 to Arg-54; Arg-98 to Arg-106; Thr-114 to Val-122; Gln-133 to Asn-141; and Leu-223 to Thr-231. SP113 Asn-19 to Gly-27; Arg-54 to Ser-62; Val-69 to Gln-77; Ser-117 to Asn-125; Gly-164 to Leu-172; Tyr-193 to Ser-201; Cys-303 to Phe-311; His-315 to Ile-323; Arg-341 to Cys-349; Ile-347 to Ser-355; Arg-403 to Phe-411; Gln-484 to Pro-492; Ser-499 to Leu-507; Ile-541 to Thr-549 Asn-622 to Ile-630; and Glu-645 to Gly-653. SP114 Gly-17 to Leu-25; His-40 to Gln-48; Arg-49 to Arg-57; Ile-65 to Pro-73; Asn-101 to Asp-111; Gly-128 to Cys-136; Phe-183 to Thr-191; and Pro-268 to Ile-276. SP115 Met-8 to Ser-16; Tyr-24 to Leu-32; Cys-68 to Leu-76; Ser-100 to Pro-108; Thr-193 to Thr-201; Gly-238 to Pro-250; Thr-280 to Phe-288; Pro-303 to Asn-312; Trp-319 to Leu-328; Leu-335 to Leu-344; Lys-395 to Ala-403; Asn-416 to Gln-424; Tyr-430 to Ser-438; Val-448 to Leu-456; Leu-460 to Thr-468; Pro-502 to Thr-510; Lys-515 to Ile-524; Gln-523 to His-532; Tyr-535 to Thr-543; Ser-559 to Pro-567; Thr-572 to Asn-580; Val-594 to Arg-602; Arg-603 to Asn-611; Thr-620 to Trp-628; and Tyr-644 to Arg-653. SP117 Ala-6 to Gly-14; Ile-19 to Thr-27; Thr-99 to Leu-107; Ser-117 to Asp-125; His-131 to Val-139; Ile-193 to Gly-201; and Val-241 to Gln-249. SP118 Ser-8 to Trp-23; His-46 to Ala-54; Asn-93 to Gly-101; Val-100 to Ser-108; Arg-155 to Asp-163; and His-192 to Leu-200. SP119 Tyr-46 to Lys-54; Ser-93 to Ser-101; Trp-108 to Asn-116; Val-121 to Glu-129; and Tyr-131 to Gln-139. SP120 Ala-57 to Lys-65; Leu-68 to Glu-76; Thr-103 to Tyr-116; Tyr-122 to Val-130; His-163 to Gly-173; Asp-188 to Ser-196; Ser-222 to Ser-231; Phe-244 to Ser-252; Pro-262 to Tyr-270; Val-283 to His-291; and Asp-298 to Leu-306. SP121 Ser-3 to Ala-11; Asp-13 to Leu-21; Ser-36 to Val-44; and Gln-136 to Met-144. SP122 Asn-28 to Lys-36; Glu-39 to Thr-50; Val-54 to Lys-62; Asn-106 to Leu-114; Phe-159 to Gly-167; Asn-172 to Arg-180; Glu-199 to Asn-207; Lys-230 to His-241; Asn-252 to Gly-263; Met-278 to Ala-287; Thr-346 to Asp-354; Lys-362 to Thr-370; Asp-392 to Asn-405; Asp-411 to Ala-424; Gly-434 to Gly-443; Tyr-484 to Glu-492; Ile-511 to Leu-519; Asn-524 to Asp-538; Glu-552 to Ile-567; Val-605 to Lys-613; Phe-697 to Ala-705; Phe-722 to Leu-730; Leu-753 to Leu-761; Asp-787 to Gln-795; Leu-858 to Asn-866; Ala-892 to Thr-901; Gly-903 to Ile-913; Ile-921 to Asn-931; Asn-938 to Pro-951; Gly-960 to Lys-970; Leu-977 to Asp-985; and Leu-988 to Pro-996. SP123 Val-4 to Asn-12; Glu-47 to Leu-55; Lys-89 to Glu-100; Ser-165 to Thr-173; Lys-234 to Val-242; Ser-258 to Ser-266; Glu-284 to Asn-292; Tyr-327 to Leu-335; Tyr-457 to Thr-465; Tyr-493 to Glu-501; Thr-506 to Tyr-514; Lys-517 to Thr-525; Asn-532 to Gly-540; and Arg-556 to Glu-564. SP124 rg-16 to Glu-24; Gln-52 to Arg-60; Asn-69 to Tyr-77; Glu-121 to Asn-129; Ala-134 to Val-142; Thr-151 to Ala-159; Asn-164 to Glu-172; His-181 to His-189; Thr-210 to Ala-218; Ser-244 to Val-252; Phe-287 to Tyr-297; Ser-312 to Thr-323; His-433 to Tyr-441; Ser-445 to Asn-453; Asn-469 to Thr-477; Asn-501 to Asn-509; Gln-536 to Ala-547; and Gln-608 to Asp-621. SP125 Ser-9 to Asp-21; Ala-28 to Leu-36; Asn-49 to Phe-57; Val-137 to Arg-145; Asn-155 to Leu-163; Glu-183 to Asp-191; Gly-202 to Tyr-210; Pro-221 to Asp-229; Phe-263 to Ala-271; Phe-300 to Gln-308; Asp-313 to Glu-321; Asn-324 to Asp-332; Ile-346 to Asn-354; Asp-362 to Lys-370; Met-402 to Gly-410; Gly-437 to Gly-445; Ser-471 to Glu-483; Gly-529 to Asp-537; Gln-555 to Val-563; and Leu-579 to Lys-587. SP126 Leu-22 to Thr-30; Val-65 to Leu-73; and Thr-75 to Asp-83. SP127 Glu-2 to Ala-12; Asp-28 to Thr-36; Val-105 to Thr-113; Lys-121 to Thr-129; Trp-138 to

Pro-146; Ser-152 to Ile-160; Lys-180 to Asp-188; Leu-194 to Asn-202; and Gly-228 to Thr-236.

TABLE-US-00003 TABLE 3 S. pneumoniae ORF Cloning Primers Primer Name SEQ ID NO: RE SP001A 227 Bam HI SP001B 228 Sal I SP004A 229 Bam HI SP004B 230 Sal I SP006A 231 Bam HI SP006B 232 Hind III SP007A 233 Bam HI SP007B 234 Hind III SP008A 235 Bgl II SP008B 236 Hind III SP009A 237 Bam HI SP009B 238 Hind III SP010A 239 Bam HI SP010B 240 Hind III SP011A 241 Bgl II SP011B 242 Pst I SP012A 243 Bam HI SP012B 244 Pst I SP013A 245 Bam HI SP013B 246 Hind III SP014A 247 Bgl II SP014B 248 Pst I SP015A 249 Bam HI SP015B 250 Pst I SP016A 251 Bam HI SP016B 252 Hind III SP017A 253 Bam HI SP017B 254 Hind III SP019A 255 Bam HI SP019B 256 Hind III SP020A 257 Bam HI SP020B 258 Hind III SP021A 259 Bam HI SP021B 260 Hind III SP022A 261 Bam HI SP022B 262 Hind III SP023A 263 Bam HI SP023B 264 Hind III SP025A 265 Bam HI SP025B 266 Sal I SP028A 267 Bam HI SP028B 268 Pst I SP030A 269 Bam HI SP030B 270 Hind III SP031A 271 Bam HI SP031B 272 Hind III SP032A 273 Bam HI SP032B 274 Pst I SP033A 275 Bgl II SP033B 276 Hind III SP034A 277 Bam HI SP034B 278 Hind III SP035A 279 Bam HI SP035B 280 Hind III SP036A 281 Bam HI SP036B 282 Hind III SP038A 283 Bam HI SP038B 284 Xho I SP039A 285 Bam HI SP039B 286 Hind III SP040A 287 Bam HI SP040B 288 Hind III SP041A 289 Bam HI SP041B 290 Hind III SP042A 291 Bam HI SP042B 292 Hind III SP043A 293 Bam HI SP043B 294 Hind III SP044A 295 Bam HI SP044B 296 Hind III SP045A 297 Bam HI SP045B 298 Sal I SP046A 299 Bam HI SP046B 300 Pst I SP048A 301 Bam HI SP048B 302 Hind III SP049A 303 Bam HI SP049B 304 Hind III SP050A 305 Bam HI SP050B 306 Hind III SP051A 307 Bam HI SP051B 308 Sal I SP052A 309 Bam HI SP052B 310 Hind III SP053A 311 Bam HI SP053B 312 Sal I SP054A 313 Bam HI SP054B 314 Hind III SP055A 315 Bam HI SP055B 316 Hind III SP056A 317 Bam HI SP056B 318 Hind III SP057A 319 Bam HI SP057B 320 Hind III SP058A 321 Bam HI SP058B 322 Sal I SP059A 323 Bam HI SP059B 324 Pst I SP060A 325 Bam HI SP060B 326 Hind III SP062A 327 Bam HI SP062B 328 Pst I SP063A 329 Bam HI SP063B 330 Hind III SP064A 331 Bam HI SP064B 332 Pst I SP065A 333 Bam HI SP065B 334 Hind III SP067A 335 Bam HI SP067B 336 Sal I SP068A 337 Bam HI SP068B 338 Sal I SP069A 339 Bam HI SP069B 340 Hind III SP070A 341 Bam HI SP070B 342 Hind III SP071A 343 Bgl II SP071B 344 Hind III SP072A 345 Bgl II SP072B 346 Hind III SP073A 347 Sal I SP073B 348 Hind III SP074A 349 Bam HI SP074B 350 Pst I SP075A 351 Bam HI SP075B 352 Hind III SP076A 353 Bam HI SP076B 354 Hind III SP077A 355 Bgl II SP077B 356 Hind III SP078A 357 Bam HI SP078B 358 Sal I SP079A 359 Bam HI SP079B 360 Pst I SP080A 361 Bam HI SP080B 362 Hind III SP081A 363 Bam HI SP081B 364 Hind III SP082A 365 Bam HI SP082B 366 Hind III SP083A 367 Bam HI SP083B 368 Bgl II SP084A 369 Bam HI SP084B 370 Hind III SP085A 371 Bam HI SP085B 372 Hind III SP086A 373 Bam HI SP086B 374 Hind III SP087A 375 Bam HI SP087B 376 Hind III SP088A 377 Bam HI SP088B 378 Hind III SP089A 379 Bam HI SP089B 380 Pst I SP090A 381 Bam HI SP090B 382 Pst I SP091A 383 Bam HI SP091B 384 Hind III SP092A 385 Bgl II SP092B 386 Hind III SP093A 387 Bam HI SP093B 388 Hind III SP094A 389 Bam HI SP094B 390 Hind III SP095A 391 Bam HI SP095B 392 Hind III SP096A 393 Bam HI SP096B 394 Hind III SP097A 395 Bam HI SP097B 396 Hind III SP098A 397 Bam HI SP098B 398 Hind III SP099A 399 Bam HI SP099B 400 Hind III SP100A 401 Bam HI SP100B 402 Pst I SP101A 403 Bam HI SP101B 404 Hind III SP102A 405 Bam HI SP102B 406 Hind III SP103A 407 Sal I SP103B 408 Pst I SP105A 409 Bam HI SP105B 410 Hind III SP106A 411 Sal I SP106B 412 Hind III SP107A 413 Bam HI SP107B 414 Hind III SP108A 415 Bam HI SP108B 416 Hind III SP109A 417 Bam HI SP109B 418 Hind III SP110A 419 Bam HI SP110B 420 Hind III SP111A 421 Bam HI SP111B 422 Hind III SP112A 423 Sal I SP112B 424 Hind III SP113A 425 Bam HI SP113B 426 Hind III SP114A 427 Bam HI SP114B 428 Hind III SP115A 429 Bam HI SP115B 430 Hind III SP117A 431 Bam HI SP117B 432 Sal I SP118A 433 Sal I SP118B 434 Pst I SP119A 435 Bam HI SP119B 436 Hind III SP120A 437 Bam HI SP120B 438 Hind III SP121A 439 Bam HI SP121B 440 Hind III SP122A 441 Bam HI SP122B 442 Sal I SP123A 443 Bam HI SP123B 444 Hind III SP124A 445 Bam HI SP124B 446 Sal I SP125A 447 Bam HI SP125B 448 Sal I SP126A 449 Bam HI SP126B 450 Hind III SP127A 451 Bam HI SP127B 452 Hind III

Sequence CWU 1

1

45411999DNAStreptococcus pneumoniae 1taaaatctac gacaataaaa atcaactcat tgctgacttg ggttctgaac gccgcgtcaa 60tgcccaagct aatgatattc ccacagattt ggttaaggca atcgtttcta tcgaagacca 120tcgcttcttc gaccacaggg ggattgatac catccgtatc ctgggagctt tcttgcgcaa 180tctgcaaagc aattccctcc aaggtggatc aactctcacc caacagttga ttaagttgac 240ttacttttca acttcgactt ccgaccagac tatttctcgt aaggctcagg aagcttggtt 300agcgattcag ttagaacaaa aagcaaccaa gcaagaaatc ttgacctact atataaataa 360ggtctacatg tctaatggga actatggaat gcagacagca gctcaaaact actatggtaa 420agacctcaat aatttaagtt tacctcagtt agccttgctg gctggaatgc ctcaggcacc 480aaaccaatat gacccctatt cacatccaga agcagcccaa gaccgccgaa acttggtctt 540atctgaaatg aaaaatcaag gctacatctc tgctgaacag tatgagaaag cagtcaatac 600accaattact gatggactac aaagtctcaa atcagcaagt aattaccctg cttacatgga 660taattacctc aaggaagtca tcaatcaagt tgaagaagaa acaggctata acctactcac 720aactgggatg gatgtctaca caaatgtaga ccaagaagct caaaaacatc tgtgggatat 780ttacaataca gacgaatacg ttgcctatcc agacgatgaa ttgcaagtcg cttctaccat 840tgttgatgtt tctaacggta aagtcattgc ccagctagga gcacgccatc agtcaagtaa 900tgtttccttc ggaattaacc aagcagtaga aacaaaccgc gactggggat caactatgaa 960accgatcaca gactatgctc ctgccttgga gtacggtgtc tacgattcaa ctgctactat 1020cgttcacgat gagccctata actaccctgg gacaaatact cctgtttata actgggatag 1080gggctacttt ggcaacatca ccttgcaata cgccctgcaa caatcgcgaa acgtcccagc 1140cgtggaaact ctaaacaagg tcggactcaa ccgcgccaag actttcctaa atggtctagg 1200aatcgactac ccaagtattc actactcaaa tgccatttca agtaacacaa ccgaatcaga 1260caaaaaatat ggagcaagta gtgaaaagat ggctgctgct tacgctgcct ttgcaaatgg 1320tggaacttac tataaaccaa tgtatatcca taaagtcgtc tttagtgatg ggagtgaaaa 1380agagttctct aatgtcggaa ctcgtgccat gaaggaaacg acagcctata tgatgaccga 1440catgatgaaa acagtcttga cttatggaac tggacgaaat gcctatcttg cttggctccc 1500tcaggctggt aaaacaggaa cctctaacta tacagacgag gaaattgaaa accacatcaa 1560gacctctcaa tttgtagcac ctgatgaact atttgctggc tatacgcgta aatattcaat 1620ggctgtatgg acaggctatt ctaaccgtct gacaccactt gtaggcaatg gccttacggt 1680cgctgccaaa gtttaccgct ctatgatgac ctacctgtct gaaggaagca atccagaaga 1740ttggaatata ccagaggggc tctacagaaa tggagaattc gtatttaaaa atggtgctcg 1800ttctacgtgg aactcacctg ctccacaaca acccccatca actgaaagtt caagctcatc 1860atcagatagt tcaacttcac agtctagctc aaccactcca agcacaaata atagtacgac 1920taccaatcct aacaataata cgcaacaatc aaatacaacc cctgatcaac aaaatcagaa 1980tcctcaacca gcacaacca 19992666PRTStreptococcus pneumoniae 2Lys Ile Tyr Asp Asn Lys Asn Gln Leu Ile Ala Asp Leu Gly Ser Glu1 5 10 15Arg Arg Val Asn Ala Gln Ala Asn Asp Ile Pro Thr Asp Leu Val Lys 20 25 30Ala Ile Val Ser Ile Glu Asp His Arg Phe Phe Asp His Arg Gly Ile 35 40 45Asp Thr Ile Arg Ile Leu Gly Ala Phe Leu Arg Asn Leu Gln Ser Asn 50 55 60Ser Leu Gln Gly Gly Ser Thr Leu Thr Gln Gln Leu Ile Lys Leu Thr65 70 75 80Tyr Phe Ser Thr Ser Thr Ser Asp Gln Thr Ile Ser Arg Lys Ala Gln 85 90 95Glu Ala Trp Leu Ala Ile Gln Leu Glu Gln Lys Ala Thr Lys Gln Glu 100 105 110Ile Leu Thr Tyr Tyr Ile Asn Lys Val Tyr Met Ser Asn Gly Asn Tyr 115 120 125Gly Met Gln Thr Ala Ala Gln Asn Tyr Tyr Gly Lys Asp Leu Asn Asn 130 135 140Leu Ser Leu Pro Gln Leu Ala Leu Leu Ala Gly Met Pro Gln Ala Pro145 150 155 160Asn Gln Tyr Asp Pro Tyr Ser His Pro Glu Ala Ala Gln Asp Arg Arg 165 170 175Asn Leu Val Leu Ser Glu Met Lys Asn Gln Gly Tyr Ile Ser Ala Glu 180 185 190Gln Tyr Glu Lys Ala Val Asn Thr Pro Ile Thr Asp Gly Leu Gln Ser 195 200 205Leu Lys Ser Ala Ser Asn Tyr Pro Ala Tyr Met Asp Asn Tyr Leu Lys 210 215 220Glu Val Ile Asn Gln Val Glu Glu Glu Thr Gly Tyr Asn Leu Leu Thr225 230 235 240Thr Gly Met Asp Val Tyr Thr Asn Val Asp Gln Glu Ala Gln Lys His 245 250 255Leu Trp Asp Ile Tyr Asn Thr Asp Glu Tyr Val Ala Tyr Pro Asp Asp 260 265 270Glu Leu Gln Val Ala Ser Thr Ile Val Asp Val Ser Asn Gly Lys Val 275 280 285Ile Ala Gln Leu Gly Ala Arg His Gln Ser Ser Asn Val Ser Phe Gly 290 295 300Ile Asn Gln Ala Val Glu Thr Asn Arg Asp Trp Gly Ser Thr Met Lys305 310 315 320Pro Ile Thr Asp Tyr Ala Pro Ala Leu Glu Tyr Gly Val Tyr Asp Ser 325 330 335Thr Ala Thr Ile Val His Asp Glu Pro Tyr Asn Tyr Pro Gly Thr Asn 340 345 350Thr Pro Val Tyr Asn Trp Asp Arg Gly Tyr Phe Gly Asn Ile Thr Leu 355 360 365Gln Tyr Ala Leu Gln Gln Ser Arg Asn Val Pro Ala Val Glu Thr Leu 370 375 380Asn Lys Val Gly Leu Asn Arg Ala Lys Thr Phe Leu Asn Gly Leu Gly385 390 395 400Ile Asp Tyr Pro Ser Ile His Tyr Ser Asn Ala Ile Ser Ser Asn Thr 405 410 415Thr Glu Ser Asp Lys Lys Tyr Gly Ala Ser Ser Glu Lys Met Ala Ala 420 425 430Ala Tyr Ala Ala Phe Ala Asn Gly Gly Thr Tyr Tyr Lys Pro Met Tyr 435 440 445Ile His Lys Val Val Phe Ser Asp Gly Ser Glu Lys Glu Phe Ser Asn 450 455 460Val Gly Thr Arg Ala Met Lys Glu Thr Thr Ala Tyr Met Met Thr Asp465 470 475 480Met Met Lys Thr Val Leu Thr Tyr Gly Thr Gly Arg Asn Ala Tyr Leu 485 490 495Ala Trp Leu Pro Gln Ala Gly Lys Thr Gly Thr Ser Asn Tyr Thr Asp 500 505 510Glu Glu Ile Glu Asn His Ile Lys Thr Ser Gln Phe Val Ala Pro Asp 515 520 525Glu Leu Phe Ala Gly Tyr Thr Arg Lys Tyr Ser Met Ala Val Trp Thr 530 535 540Gly Tyr Ser Asn Arg Leu Thr Pro Leu Val Gly Asn Gly Leu Thr Val545 550 555 560Ala Ala Lys Val Tyr Arg Ser Met Met Thr Tyr Leu Ser Glu Gly Ser 565 570 575Asn Pro Glu Asp Trp Asn Ile Pro Glu Gly Leu Tyr Arg Asn Gly Glu 580 585 590Phe Val Phe Lys Asn Gly Ala Arg Ser Thr Trp Asn Ser Pro Ala Pro 595 600 605Gln Gln Pro Pro Ser Thr Glu Ser Ser Ser Ser Ser Ser Asp Ser Ser 610 615 620Thr Ser Gln Ser Ser Ser Thr Thr Pro Ser Thr Asn Asn Ser Thr Thr625 630 635 640Thr Asn Pro Asn Asn Asn Thr Gln Gln Ser Asn Thr Thr Pro Asp Gln 645 650 655Gln Asn Gln Asn Pro Gln Pro Ala Gln Pro 660 66531714DNAStreptococcus pneumoniae 3aaattacaat acggactatg aattgacctc tggagaaaaa ttacctcttc ctaaagagat 60ttcaggttac acttatattg gatatatcaa agagggaaaa acgacttctg agtctgaagt 120aagtaatcaa aagagttcag ttgccactcc tacaaaacaa caaaaggtgg attataatgt 180tacaccgaat tttgtagacc atccatcaac agtacaagct attcaggaac aaacacctgt 240ttcttcaact aagccgacag aagttcaagt agttgaaaaa cctttctcta ctgaattaat 300caatccaaga aaagaagaga aacaatcttc agattctcaa gaacaattag ccgaacataa 360gaatctagaa acgaagaaag aggagaagat ttctccaaaa gaaaagactg gggtaaatac 420attaaatcca caggatgaag ttttatcagg tcaattgaac aaacctgaac tcttatatcg 480tgaggaaact atggagacaa aaatagattt tcaagaagaa attcaagaaa atcctgattt 540agctgaagga actgtaagag taaaacaaga aggtaaatta ggtaagaaag ttgaaatcgt 600cagaatattc tctgtaaaca aggaagaagt ttcgcgagaa attgtttcaa cttcaacgac 660tgcgcctagt ccaagaatag tcgaaaaagg tactaaaaaa actcaagtta taaaggaaca 720acctgagact ggtgtagaac ataaggacgt acagtctgga gctattgttg aacccgcaat 780tcagcctgag ttgcccgaag ctgtagtaag tgacaaaggc gaaccagaag ttcaacctac 840attacccgaa gcagttgtga ccgacaaagg tgagactgag gttcaaccag agtcgccaga 900tactgtggta agtgataaag gtgaaccaga gcaggtagca ccgcttccag aatataaggg 960taatattgag caagtaaaac ctgaaactcc ggttgagaag accaaagaac aaggtccaga 1020aaaaactgaa gaagttccag taaaaccaac agaagaaaca ccagtaaatc caaatgaagg 1080tactacagaa ggaacctcaa ttcaagaagc agaaaatcca gttcaacctg cagaagaatc 1140aacaacgaat tcagagaaag tatcaccaga tacatctagc aaaaatactg gggaagtgtc 1200cagtaatcct agtgattcga caacctcagt tggagaatca aataaaccag aacataatga 1260ctctaaaaat gaaaattcag aaaaaactgt agaagaagtt ccagtaaatc caaatgaagg 1320cacagtagaa ggtacctcaa atcaagaaac agaaaaacca gttcaacctg cagaagaaac 1380acaaacaaac tctgggaaaa tagctaacga aaatactgga gaagtatcca ataaacctag 1440tgattcaaaa ccaccagttg aagaatcaaa tcaaccagaa aaaaacggaa ctgcaacaaa 1500accagaaaat tcaggtaata caacatcaga gaatggacaa acagaaccag aaccatcaaa 1560cggaaattca actgaggatg tttcaaccga atcaaacaca tccaattcaa atggaaacga 1620agaaattaaa caagaaaatg aactagaccc tgataaaaag gtagaagaac cagagaaaac 1680acttgaatta agaaatgttt ccgacctaga gtta 17144571PRTStreptococcus pneumoniae 4Asn Tyr Asn Thr Asp Tyr Glu Leu Thr Ser Gly Glu Lys Leu Pro Leu1 5 10 15Pro Lys Glu Ile Ser Gly Tyr Thr Tyr Ile Gly Tyr Ile Lys Glu Gly 20 25 30Lys Thr Thr Ser Glu Ser Glu Val Ser Asn Gln Lys Ser Ser Val Ala 35 40 45Thr Pro Thr Lys Gln Gln Lys Val Asp Tyr Asn Val Thr Pro Asn Phe 50 55 60Val Asp His Pro Ser Thr Val Gln Ala Ile Gln Glu Gln Thr Pro Val65 70 75 80Ser Ser Thr Lys Pro Thr Glu Val Gln Val Val Glu Lys Pro Phe Ser 85 90 95Thr Glu Leu Ile Asn Pro Arg Lys Glu Glu Lys Gln Ser Ser Asp Ser 100 105 110Gln Glu Gln Leu Ala Glu His Lys Asn Leu Glu Thr Lys Lys Glu Glu 115 120 125Lys Ile Ser Pro Lys Glu Lys Thr Gly Val Asn Thr Leu Asn Pro Gln 130 135 140Asp Glu Val Leu Ser Gly Gln Leu Asn Lys Pro Glu Leu Leu Tyr Arg145 150 155 160Glu Glu Thr Met Glu Thr Lys Ile Asp Phe Gln Glu Glu Ile Gln Glu 165 170 175Asn Pro Asp Leu Ala Glu Gly Thr Val Arg Val Lys Gln Glu Gly Lys 180 185 190Leu Gly Lys Lys Val Glu Ile Val Arg Ile Phe Ser Val Asn Lys Glu 195 200 205Glu Val Ser Arg Glu Ile Val Ser Thr Ser Thr Thr Ala Pro Ser Pro 210 215 220Arg Ile Val Glu Lys Gly Thr Lys Lys Thr Gln Val Ile Lys Glu Gln225 230 235 240Pro Glu Thr Gly Val Glu His Lys Asp Val Gln Ser Gly Ala Ile Val 245 250 255Glu Pro Ala Ile Gln Pro Glu Leu Pro Glu Ala Val Val Ser Asp Lys 260 265 270Gly Glu Pro Glu Val Gln Pro Thr Leu Pro Glu Ala Val Val Thr Asp 275 280 285Lys Gly Glu Thr Glu Val Gln Pro Glu Ser Pro Asp Thr Val Val Ser 290 295 300Asp Lys Gly Glu Pro Glu Gln Val Ala Pro Leu Pro Glu Tyr Lys Gly305 310 315 320Asn Ile Glu Gln Val Lys Pro Glu Thr Pro Val Glu Lys Thr Lys Glu 325 330 335Gln Gly Pro Glu Lys Thr Glu Glu Val Pro Val Lys Pro Thr Glu Glu 340 345 350Thr Pro Val Asn Pro Asn Glu Gly Thr Thr Glu Gly Thr Ser Ile Gln 355 360 365Glu Ala Glu Asn Pro Val Gln Pro Ala Glu Glu Ser Thr Thr Asn Ser 370 375 380Glu Lys Val Ser Pro Asp Thr Ser Ser Lys Asn Thr Gly Glu Val Ser385 390 395 400Ser Asn Pro Ser Asp Ser Thr Thr Ser Val Gly Glu Ser Asn Lys Pro 405 410 415Glu His Asn Asp Ser Lys Asn Glu Asn Ser Glu Lys Thr Val Glu Glu 420 425 430Val Pro Val Asn Pro Asn Glu Gly Thr Val Glu Gly Thr Ser Asn Gln 435 440 445Glu Thr Glu Lys Pro Val Gln Pro Ala Glu Glu Thr Gln Thr Asn Ser 450 455 460Gly Lys Ile Ala Asn Glu Asn Thr Gly Glu Val Ser Asn Lys Pro Ser465 470 475 480Asp Ser Lys Pro Pro Val Glu Glu Ser Asn Gln Pro Glu Lys Asn Gly 485 490 495Thr Ala Thr Lys Pro Glu Asn Ser Gly Asn Thr Thr Ser Glu Asn Gly 500 505 510Gln Thr Glu Pro Glu Pro Ser Asn Gly Asn Ser Thr Glu Asp Val Ser 515 520 525Thr Glu Ser Asn Thr Ser Asn Ser Asn Gly Asn Glu Glu Ile Lys Gln 530 535 540Glu Asn Glu Leu Asp Pro Asp Lys Lys Val Glu Glu Pro Glu Lys Thr545 550 555 560Leu Glu Leu Arg Asn Val Ser Asp Leu Glu Leu 565 5705748DNAStreptococcus pneumoniae 5tgagaatcaa gctacaccca aagagactag cgctcaaaag acaatcgtcc ttgctacagc 60tggcgacgtg ccaccatttg actacgaaga caagggcaat ctgacaggct ttgatatcga 120agttttaaag gcagtagatg aaaaactcag cgactacgag attcaattcc aaagaaccgc 180ctgggagagc atcttcccag gacttgattc tggtcactat caggctgcgg ccaataactt 240gagttacaca aaagagcgtg ctgaaaaata cctttactcg cttccaattt ccaacaatcc 300cctcgtcctt gtcagcaaca agaaaaatcc tttgacttct cttgaccaga tcgctggtaa 360aacaacacaa gaggataccg gaacttctaa cgctcaattc atcaataact ggaatcagaa 420acacactgat aatcccgcta caattaattt ttctggtgag gatattggta aacgaatcct 480agaccttgct aacggagagt ttgatttcct agtttttgac aaggtatccg ttcaaaagat 540tatcaaggac cgtggtttag acctctcagt cgttgattta ccttctgcag atagccccag 600caattatatc attttctcaa gcgaccaaaa agagtttaaa gagcaatttg ataaagcgct 660caaagaactc tatcaagacg gaacccttga aaaactcagc aatacctatc taggtggttc 720ttacctccca gatcaatctc agttacaa 7486249PRTStreptococcus pneumoniae 6Glu Asn Gln Ala Thr Pro Lys Glu Thr Ser Ala Gln Lys Thr Ile Val1 5 10 15Leu Ala Thr Ala Gly Asp Val Pro Pro Phe Asp Tyr Glu Asp Lys Gly 20 25 30Asn Leu Thr Gly Phe Asp Ile Glu Val Leu Lys Ala Val Asp Glu Lys 35 40 45Leu Ser Asp Tyr Glu Ile Gln Phe Gln Arg Thr Ala Trp Glu Ser Ile 50 55 60Phe Pro Gly Leu Asp Ser Gly His Tyr Gln Ala Ala Ala Asn Asn Leu65 70 75 80Ser Tyr Thr Lys Glu Arg Ala Glu Lys Tyr Leu Tyr Ser Leu Pro Ile 85 90 95Ser Asn Asn Pro Leu Val Leu Val Ser Asn Lys Lys Asn Pro Leu Thr 100 105 110Ser Leu Asp Gln Ile Ala Gly Lys Thr Thr Gln Glu Asp Thr Gly Thr 115 120 125Ser Asn Ala Gln Phe Ile Asn Asn Trp Asn Gln Lys His Thr Asp Asn 130 135 140Pro Ala Thr Ile Asn Phe Ser Gly Glu Asp Ile Gly Lys Arg Ile Leu145 150 155 160Asp Leu Ala Asn Gly Glu Phe Asp Phe Leu Val Phe Asp Lys Val Ser 165 170 175Val Gln Lys Ile Ile Lys Asp Arg Gly Leu Asp Leu Ser Val Val Asp 180 185 190Leu Pro Ser Ala Asp Ser Pro Ser Asn Tyr Ile Ile Phe Ser Ser Asp 195 200 205Gln Lys Glu Phe Lys Glu Gln Phe Asp Lys Ala Leu Lys Glu Leu Tyr 210 215 220Gln Asp Gly Thr Leu Glu Lys Leu Ser Asn Thr Tyr Leu Gly Gly Ser225 230 235 240Tyr Leu Pro Asp Gln Ser Gln Leu Gln 2457985DNAStreptococcus pneumoniae 7tggtaaccgc tcttctcgta acgcagcttc atcttctgat gtgaagacaa aagcagcaat 60cgtcactgat actggtggtg ttgatgacaa atcattcaac caatcagctt gggaaggttt 120gcaggcttgg ggtaaagaac acaatctttc aaaagataac ggtttcactt acttccaatc 180aacaagtgaa gctgactacg ctaacaactt gcaacaagcg gctggaagtt acaacctaat 240cttcggtgtt ggttttgccc ttaataatgc agttaaagat gcagcaaaag aacacactga 300cttgaactat gtcttgattg atgatgtgat taaagaccaa aagaatgttg cgagcgtaac 360tttcgctgat aatgagtcag gttaccttgc aggtgtggct gcagcaaaaa caactaagac 420aaaacaagtt ggttttgtag gtggtatcga atctgaagtt atctctcgtt ttgaagcagg 480attcaaggct ggtgttgcgt cagtagaccc atctatcaaa gtccaagttg actacgctgg 540ttcatttggt gatgcggcta aaggtaaaac aattgcagcc gcacaatacg cagccggtgc 600agatattgtt taccaagtag ctggtggtac aggtgcaggt gtctttgcag aggcaaaatc 660tctcaacgaa agccgtcctg aaaatgaaaa agtttgggtt atcggtgttg atcgtgacca 720agaagcagaa ggtaaataca cttctaaaga tggcaaagaa tcaaactttg ttcttgtatc 780tactttgaaa caagttggta caactgtaaa agatatttct aacaaggcag aaagaggaga 840attccctggc ggtcaagtga tcgtttactc attgaaggat aaaggggttg acttggcagt 900aacaaacctt tcagaagaag gtaaaaaagc tgtcgaagat gcaaaagcta aaatccttga 960tggaagcgta aaagttcctg aaaaa 9858328PRTStreptococcus pneumoniae 8Gly Asn Arg Ser Ser Arg Asn Ala Ala Ser Ser Ser Asp Val Lys Thr1 5 10 15Lys Ala Ala Ile Val Thr Asp Thr Gly Gly Val Asp Asp Lys Ser Phe 20 25 30Asn Gln Ser Ala

Trp Glu Gly Leu Gln Ala Trp Gly Lys Glu His Asn 35 40 45Leu Ser Lys Asp Asn Gly Phe Thr Tyr Phe Gln Ser Thr Ser Glu Ala 50 55 60Asp Tyr Ala Asn Asn Leu Gln Gln Ala Ala Gly Ser Tyr Asn Leu Ile65 70 75 80Phe Gly Val Gly Phe Ala Leu Asn Asn Ala Val Lys Asp Ala Ala Lys 85 90 95Glu His Thr Asp Leu Asn Tyr Val Leu Ile Asp Asp Val Ile Lys Asp 100 105 110Gln Lys Asn Val Ala Ser Val Thr Phe Ala Asp Asn Glu Ser Gly Tyr 115 120 125Leu Ala Gly Val Ala Ala Ala Lys Thr Thr Lys Thr Lys Gln Val Gly 130 135 140Phe Val Gly Gly Ile Glu Ser Glu Val Ile Ser Arg Phe Glu Ala Gly145 150 155 160Phe Lys Ala Gly Val Ala Ser Val Asp Pro Ser Ile Lys Val Gln Val 165 170 175Asp Tyr Ala Gly Ser Phe Gly Asp Ala Ala Lys Gly Lys Thr Ile Ala 180 185 190Ala Ala Gln Tyr Ala Ala Gly Ala Asp Ile Val Tyr Gln Val Ala Gly 195 200 205Gly Thr Gly Ala Gly Val Phe Ala Glu Ala Lys Ser Leu Asn Glu Ser 210 215 220Arg Pro Glu Asn Glu Lys Val Trp Val Ile Gly Val Asp Arg Asp Gln225 230 235 240Glu Ala Glu Gly Lys Tyr Thr Ser Lys Asp Gly Lys Glu Ser Asn Phe 245 250 255Val Leu Val Ser Thr Leu Lys Gln Val Gly Thr Thr Val Lys Asp Ile 260 265 270Ser Asn Lys Ala Glu Arg Gly Glu Phe Pro Gly Gly Gln Val Ile Val 275 280 285Tyr Ser Leu Lys Asp Lys Gly Val Asp Leu Ala Val Thr Asn Leu Ser 290 295 300Glu Glu Gly Lys Lys Ala Val Glu Asp Ala Lys Ala Lys Ile Leu Asp305 310 315 320Gly Ser Val Lys Val Pro Glu Lys 32591404DNAStreptococcus pneumoniaemisc_feature(871)..(871)n is a, c, g, or t 9tgtggaaatt tgacaggtaa cagcaaaaaa gctgctgatt caggtgacaa acctgttatc 60aaaatgtacc aaatcggtga caaaccagac aacttggatg aattgttagc aaatgccaac 120aaaatcattg aagaaaaagt tggtgccaaa ttggatatcc aataccttgg ctggggtgac 180tatggtaaga aaatgtcagt tatcacatca tctggtgaaa actatgatat tgcctttgca 240gataactata ttgtaaatgc tcaaaaaggt gcttacgctg acttgacaga attgtacaaa 300aaagaaggta aagaccttta caaagcactt gacccagctt acatcaaggg taatactgta 360aatggtaaga tttacgctgt tccagttgca gccaacgttg catcatctca aaactttgcc 420ttcaacggaa ctctccttgc taaatatggt atcgatattt caggtgttac ttcttacgaa 480actcttgagc cagtcttgaa acaaatcaaa gaaaaagctc cagacgtagt accatttgct 540attggtaaag ttttcatccc atctgataat tttgactacc cagtagcaaa cggtcttcca 600ttcgttatcg accttgaagg cgatactact aaagttgtaa accgttacga agtgcctcgt 660ttcaaagaac acttgaagac tcttcacaaa ttctatgaag ctggctacat tccaaaagac 720gtcgcaacaa gcgatacttc ctttgacctt caacaagata cttggttcgt tcgtgaagaa 780acagtaggac cagctgacta cggtaacagc ttgctttcac gtgttgccaa caaagatatc 840caaatcaaac caattactaa cttcatcaag naaaaccaaa caacacaagt tgctaacttt 900gtcatctcaa acaactctaa gaacaaagaa aaatcaatgg aaatcttgaa cctcttgaat 960acgaacccag aactcttgaa cggtcttgtt tacggtccag aaggcaagaa ctgggaaaaa 1020attgaaggta aagaaaaccg tgttcgcgtt cttgatggct acaaaggaaa cactcacatg 1080ggtggatgga acactggtaa caactggatc ctttacatca acgaaaacgt tacagaccaa 1140caaatcgaaa attctaagaa agaattggca gaagctaaag aatctccagc gcttggattt 1200atcttcaata ctgacaatgt gaaatctgaa atctcagcta ttgctaacac aatgcaacaa 1260tttgatacag ctatcaacac tggtactgta gacccagata aagcgattcc agaattgatg 1320gaaaaattga aatctgaagg tgcctacgaa aaagtattga acgaaatgca aaaacaatac 1380gatgaattct tgaaaaacaa aaaa 140410468PRTStreptococcus pneumoniaeSITE(291)..(291)Xaa can be any naturally occurring amino acid 10Cys Gly Asn Leu Thr Gly Asn Ser Lys Lys Ala Ala Asp Ser Gly Asp1 5 10 15Lys Pro Val Ile Lys Met Tyr Gln Ile Gly Asp Lys Pro Asp Asn Leu 20 25 30Asp Glu Leu Leu Ala Asn Ala Asn Lys Ile Ile Glu Glu Lys Val Gly 35 40 45Ala Lys Leu Asp Ile Gln Tyr Leu Gly Trp Gly Asp Tyr Gly Lys Lys 50 55 60Met Ser Val Ile Thr Ser Ser Gly Glu Asn Tyr Asp Ile Ala Phe Ala65 70 75 80Asp Asn Tyr Ile Val Asn Ala Gln Lys Gly Ala Tyr Ala Asp Leu Thr 85 90 95Glu Leu Tyr Lys Lys Glu Gly Lys Asp Leu Tyr Lys Ala Leu Asp Pro 100 105 110Ala Tyr Ile Lys Gly Asn Thr Val Asn Gly Lys Ile Tyr Ala Val Pro 115 120 125Val Ala Ala Asn Val Ala Ser Ser Gln Asn Phe Ala Phe Asn Gly Thr 130 135 140Leu Leu Ala Lys Tyr Gly Ile Asp Ile Ser Gly Val Thr Ser Tyr Glu145 150 155 160Thr Leu Glu Pro Val Leu Lys Gln Ile Lys Glu Lys Ala Pro Asp Val 165 170 175Val Pro Phe Ala Ile Gly Lys Val Phe Ile Pro Ser Asp Asn Phe Asp 180 185 190Tyr Pro Val Ala Asn Gly Leu Pro Phe Val Ile Asp Leu Glu Gly Asp 195 200 205Thr Thr Lys Val Val Asn Arg Tyr Glu Val Pro Arg Phe Lys Glu His 210 215 220Leu Lys Thr Leu His Lys Phe Tyr Glu Ala Gly Tyr Ile Pro Lys Asp225 230 235 240Val Ala Thr Ser Asp Thr Ser Phe Asp Leu Gln Gln Asp Thr Trp Phe 245 250 255Val Arg Glu Glu Thr Val Gly Pro Ala Asp Tyr Gly Asn Ser Leu Leu 260 265 270Ser Arg Val Ala Asn Lys Asp Ile Gln Ile Lys Pro Ile Thr Asn Phe 275 280 285Ile Lys Xaa Asn Gln Thr Thr Gln Val Ala Asn Phe Val Ile Ser Asn 290 295 300Asn Ser Lys Asn Lys Glu Lys Ser Met Glu Ile Leu Asn Leu Leu Asn305 310 315 320Thr Asn Pro Glu Leu Leu Asn Gly Leu Val Tyr Gly Pro Glu Gly Lys 325 330 335Asn Trp Glu Lys Ile Glu Gly Lys Glu Asn Arg Val Arg Val Leu Asp 340 345 350Gly Tyr Lys Gly Asn Thr His Met Gly Gly Trp Asn Thr Gly Asn Asn 355 360 365Trp Ile Leu Tyr Ile Asn Glu Asn Val Thr Asp Gln Gln Ile Glu Asn 370 375 380Ser Lys Lys Glu Leu Ala Glu Ala Lys Glu Ser Pro Ala Leu Gly Phe385 390 395 400Ile Phe Asn Thr Asp Asn Val Lys Ser Glu Ile Ser Ala Ile Ala Asn 405 410 415Thr Met Gln Gln Phe Asp Thr Ala Ile Asn Thr Gly Thr Val Asp Pro 420 425 430Asp Lys Ala Ile Pro Glu Leu Met Glu Lys Leu Lys Ser Glu Gly Ala 435 440 445Tyr Glu Lys Val Leu Asn Glu Met Gln Lys Gln Tyr Asp Glu Phe Leu 450 455 460Lys Asn Lys Lys46511937DNAStreptococcus pneumoniae 11tggtcaagga actgcttcta aagacaacaa agaggcagaa cttaagaagg ttgactttat 60cctagactgg acaccaaata ccaaccacac agggctttat gttgccaagg aaaaaggtta 120tttcaaagaa gctggagtgg atgttgattt gaaattgcca ccagaagaaa gttcttctga 180cttggttatc aacggaaagg caccatttgc agtgtatttc caagactaca tggctaagaa 240attggaaaaa ggagcaggaa tcactgccgt tgcagctatt gttgaacaca atacatcagg 300aatcatctct cgtaaatctg ataatgtaag cagtccaaaa gacttggttg gtaagaaata 360tgggacatgg aatgacccaa ctgaacttgc tatgttgaaa accttggtag aatctcaagg 420tggagacttt gagaaggttg aaaaagtacc aaataacgac tcaaactcaa tcacaccgat 480tgccaatggc gtctttgata ctgcttggat ttactacggt tgggatggta tccttgctaa 540atctcaaggt gtagatgcta acttcatgta cttgaaagac tatgtcaagg agtttgacta 600ctattcacca gttatcatcg caaacaacga ctatctgaaa gataacaaag aagaagctcg 660caaagtcatc caagccatca aaaaaggcta ccaatatgcc atggaacatc cagaagaagc 720tgcagatatt ctcatcaaga atgcacctga actcaaggaa aaacgtgact ttgtcatcga 780atctcaaaaa tacttgtcaa aagaatacgc aagcgacaag gaaaaatggg gtcaatttga 840cgcagctcgc tggaatgctt tctacaaatg ggataaagaa aatggtatcc ttaaagaaga 900cttgacagac aaaggcttca ccaacgaatt tgtgaaa 93712312PRTStreptococcus pneumoniae 12Gly Gln Gly Thr Ala Ser Lys Asp Asn Lys Glu Ala Glu Leu Lys Lys1 5 10 15Val Asp Phe Ile Leu Asp Trp Thr Pro Asn Thr Asn His Thr Gly Leu 20 25 30Tyr Val Ala Lys Glu Lys Gly Tyr Phe Lys Glu Ala Gly Val Asp Val 35 40 45Asp Leu Lys Leu Pro Pro Glu Glu Ser Ser Ser Asp Leu Val Ile Asn 50 55 60Gly Lys Ala Pro Phe Ala Val Tyr Phe Gln Asp Tyr Met Ala Lys Lys65 70 75 80Leu Glu Lys Gly Ala Gly Ile Thr Ala Val Ala Ala Ile Val Glu His 85 90 95Asn Thr Ser Gly Ile Ile Ser Arg Lys Ser Asp Asn Val Ser Ser Pro 100 105 110Lys Asp Leu Val Gly Lys Lys Tyr Gly Thr Trp Asn Asp Pro Thr Glu 115 120 125Leu Ala Met Leu Lys Thr Leu Val Glu Ser Gln Gly Gly Asp Phe Glu 130 135 140Lys Val Glu Lys Val Pro Asn Asn Asp Ser Asn Ser Ile Thr Pro Ile145 150 155 160Ala Asn Gly Val Phe Asp Thr Ala Trp Ile Tyr Tyr Gly Trp Asp Gly 165 170 175Ile Leu Ala Lys Ser Gln Gly Val Asp Ala Asn Phe Met Tyr Leu Lys 180 185 190Asp Tyr Val Lys Glu Phe Asp Tyr Tyr Ser Pro Val Ile Ile Ala Asn 195 200 205Asn Asp Tyr Leu Lys Asp Asn Lys Glu Glu Ala Arg Lys Val Ile Gln 210 215 220Ala Ile Lys Lys Gly Tyr Gln Tyr Ala Met Glu His Pro Glu Glu Ala225 230 235 240Ala Asp Ile Leu Ile Lys Asn Ala Pro Glu Leu Lys Glu Lys Arg Asp 245 250 255Phe Val Ile Glu Ser Gln Lys Tyr Leu Ser Lys Glu Tyr Ala Ser Asp 260 265 270Lys Glu Lys Trp Gly Gln Phe Asp Ala Ala Arg Trp Asn Ala Phe Tyr 275 280 285Lys Trp Asp Lys Glu Asn Gly Ile Leu Lys Glu Asp Leu Thr Asp Lys 290 295 300Gly Phe Thr Asn Glu Phe Val Lys305 31013799DNAStreptococcus pneumoniae 13tagctcaggt ggaaacgctg gttcatcctc tggaaaaaca actgccaaag ctcgcactat 60cgatgaaatc aaaaaaagcg gtgaactgcg aatcgccgtg tttggagata aaaaaccgtt 120tggctacgtt gacaatgatg gttctaccaa ggtacgctac gatattgaac tagggaacca 180actagctcaa gaccttggtg tcaaggttaa atacatttca gtcgatgctg ccaaccgtgc 240ggaatacttg atttcaaaca aggtagatat tactcttgct aactttacag taactgacga 300acgtaagaaa caagttgatt ttgcccttcc atatatgaaa gtttctctgg gtgtcgtatc 360acctaagact ggtctcatta cagacgtcaa acaacttgaa ggtaaaacct taattgtcac 420aaaaggaacg actgctgaga cttattttga aaagaatcat ccagaaatca aactccaaaa 480atacgaccaa tacagtgact cttaccaagc tcttcttgac ggacgtggag atgccttttc 540aactgacaat acggaagttc tagcttgggc gcttgaaaat aaaggatttg aagtaggaat 600tacttccctc ggtgatcccg ataccattgc ggcagcagtt caaaaaggca accaagaatt 660gctagacttc atcaataaag atattgaaaa attaggcaag gaaaacttct tccacaaggc 720ctatgaaaag acacttcacc caacctacgg tgacgctgct aaagcagatg acctggttgt 780tgaaggtgga aaagttgat 79914266PRTStreptococcus pneumoniae 14Ser Ser Gly Gly Asn Ala Gly Ser Ser Ser Gly Lys Thr Thr Ala Lys1 5 10 15Ala Arg Thr Ile Asp Glu Ile Lys Lys Ser Gly Glu Leu Arg Ile Ala 20 25 30Val Phe Gly Asp Lys Lys Pro Phe Gly Tyr Val Asp Asn Asp Gly Ser 35 40 45Thr Lys Val Arg Tyr Asp Ile Glu Leu Gly Asn Gln Leu Ala Gln Asp 50 55 60Leu Gly Val Lys Val Lys Tyr Ile Ser Val Asp Ala Ala Asn Arg Ala65 70 75 80Glu Tyr Leu Ile Ser Asn Lys Val Asp Ile Thr Leu Ala Asn Phe Thr 85 90 95Val Thr Asp Glu Arg Lys Lys Gln Val Asp Phe Ala Leu Pro Tyr Met 100 105 110Lys Val Ser Leu Gly Val Val Ser Pro Lys Thr Gly Leu Ile Thr Asp 115 120 125Val Lys Gln Leu Glu Gly Lys Thr Leu Ile Val Thr Lys Gly Thr Thr 130 135 140Ala Glu Thr Tyr Phe Glu Lys Asn His Pro Glu Ile Lys Leu Gln Lys145 150 155 160Tyr Asp Gln Tyr Ser Asp Ser Tyr Gln Ala Leu Leu Asp Gly Arg Gly 165 170 175Asp Ala Phe Ser Thr Asp Asn Thr Glu Val Leu Ala Trp Ala Leu Glu 180 185 190Asn Lys Gly Phe Glu Val Gly Ile Thr Ser Leu Gly Asp Pro Asp Thr 195 200 205Ile Ala Ala Ala Val Gln Lys Gly Asn Gln Glu Leu Leu Asp Phe Ile 210 215 220Asn Lys Asp Ile Glu Lys Leu Gly Lys Glu Asn Phe Phe His Lys Ala225 230 235 240Tyr Glu Lys Thr Leu His Pro Thr Tyr Gly Asp Ala Ala Lys Ala Asp 245 250 255Asp Leu Val Val Glu Gly Gly Lys Val Asp 260 265151189DNAStreptococcus pneumoniae 15ctccaactat ggtaaatctg cggatggcac agtgaccatc gagtatttca accagaaaaa 60agaaatgacc aaaaccttgg aagaaatcac tcgtgatttt gagaaggaaa accctaagat 120caaggtcaaa gtcgtcaatg taccaaatgc tggtgaagta ttgaagacac gcgttctcgc 180aggagatgtg cctgatgtgg tcaatattta cccacagtcc atcgaactgc aagaatgggc 240aaaagcaggt gtttttgaag atttgagcaa caaagactac ctgaaacgcg tgaaaaatgg 300ctacgctgaa aaatatgctg taaacgaaaa agtttacaac gttcctttta cagctaatgc 360ttatggaatt tactacaaca aagataaatt cgaagaactg ggcttgaagg ttcctgaaac 420ctgggatgaa tttgaacagt tagtcaaaga tatcgttgct aaaggacaaa caccatttgg 480aattgcaggt gcagatgctt ggacactcaa tggttacaat caattagcct ttgcgacagc 540aacaggtgga ggaaaagaag caaatcaata ccttcgttat tctcaaccaa atgccattaa 600attgtcggat ccgattatga aagatgatat caaggtcatg gacatccttc gcatcaatgg 660atctaagcaa aagaactggg aaggtgctgg ctataccgat gttatcggag ccttcgcacg 720tggggatgtc ctcatgacac caaatgggtc ttgggcgatc acagcgatta atgaacaaaa 780accgaacttt aagattggga ccttcatgat tccaggaaaa gaaaaaggac aaagcttaac 840cgttggtgcg ggagacttgg catggtctat ctcagccacc accaaacatc caaaagaagc 900caatgccttt gtggaatata tgacccgtcc agaagtcatg caaaaatact acgatgtgga 960cggatctcca acagcgatcg aaggggtcaa acaagcagga gaagattcac cgcttgctgg 1020tatgaccgaa tatgccttta cggatcgtca cttggtctgg ttgcaacaat actggaccag 1080tgaagcagac ttccatacct tgaccatgaa ctatgtcttg accggtgata aacaaggcat 1140ggtcaatgat ttgaatgcct tctttaaccc gatgaaagcg gatgtggat 118916396PRTStreptococcus pneumoniae 16Ser Asn Tyr Gly Lys Ser Ala Asp Gly Thr Val Thr Ile Glu Tyr Phe1 5 10 15Asn Gln Lys Lys Glu Met Thr Lys Thr Leu Glu Glu Ile Thr Arg Asp 20 25 30Phe Glu Lys Glu Asn Pro Lys Ile Lys Val Lys Val Val Asn Val Pro 35 40 45Asn Ala Gly Glu Val Leu Lys Thr Arg Val Leu Ala Gly Asp Val Pro 50 55 60Asp Val Val Asn Ile Tyr Pro Gln Ser Ile Glu Leu Gln Glu Trp Ala65 70 75 80Lys Ala Gly Val Phe Glu Asp Leu Ser Asn Lys Asp Tyr Leu Lys Arg 85 90 95Val Lys Asn Gly Tyr Ala Glu Lys Tyr Ala Val Asn Glu Lys Val Tyr 100 105 110Asn Val Pro Phe Thr Ala Asn Ala Tyr Gly Ile Tyr Tyr Asn Lys Asp 115 120 125Lys Phe Glu Glu Leu Gly Leu Lys Val Pro Glu Thr Trp Asp Glu Phe 130 135 140Glu Gln Leu Val Lys Asp Ile Val Ala Lys Gly Gln Thr Pro Phe Gly145 150 155 160Ile Ala Gly Ala Asp Ala Trp Thr Leu Asn Gly Tyr Asn Gln Leu Ala 165 170 175Phe Ala Thr Ala Thr Gly Gly Gly Lys Glu Ala Asn Gln Tyr Leu Arg 180 185 190Tyr Ser Gln Pro Asn Ala Ile Lys Leu Ser Asp Pro Ile Met Lys Asp 195 200 205Asp Ile Lys Val Met Asp Ile Leu Arg Ile Asn Gly Ser Lys Gln Lys 210 215 220Asn Trp Glu Gly Ala Gly Tyr Thr Asp Val Ile Gly Ala Phe Ala Arg225 230 235 240Gly Asp Val Leu Met Thr Pro Asn Gly Ser Trp Ala Ile Thr Ala Ile 245 250 255Asn Glu Gln Lys Pro Asn Phe Lys Ile Gly Thr Phe Met Ile Pro Gly 260 265 270Lys Glu Lys Gly Gln Ser Leu Thr Val Gly Ala Gly Asp Leu Ala Trp 275 280 285Ser Ile Ser Ala Thr Thr Lys His Pro Lys Glu Ala Asn Ala Phe Val 290 295 300Glu Tyr Met Thr Arg Pro Glu Val Met Gln Lys Tyr Tyr Asp Val Asp305 310 315 320Gly Ser Pro Thr Ala Ile Glu Gly Val Lys Gln Ala Gly Glu Asp Ser 325 330 335Pro Leu Ala Gly Met Thr Glu Tyr Ala Phe Thr Asp Arg His Leu Val 340 345 350Trp

Leu Gln Gln Tyr Trp Thr Ser Glu Ala Asp Phe His Thr Leu Thr 355 360 365Met Asn Tyr Val Leu Thr Gly Asp Lys Gln Gly Met Val Asn Asp Leu 370 375 380Asn Ala Phe Phe Asn Pro Met Lys Ala Asp Val Asp385 390 39517775DNAStreptococcus pneumoniae 17tgggaaaaat tctagcgaaa ctagtggaga taattggtca aagtaccagt ctaacaagtc 60tattactatt ggatttgata gtacttttgt tccaatggga tttgctcaga aagatggttc 120ttatgcagga tttgatattg atttagctac agctgttttt gaaaaatacg gaatcacggt 180aaattggcaa ccgattgatt gggatttgaa agaagctgaa ttgacaaaag gaacgattga 240tctgatttgg aatggctatt ccgctacaga cgaacgccgt gaaaaggtgg ctttcagtaa 300ctcatatatg aagaatgagc aggtattggt tacgaagaaa tcatctggta tcacgactgc 360aaaggatatg actggaaaga cattaggagc tcaagctggt tcatctggtt atgcggactt 420tgaagcaaat ccagaaattt tgaagaatat tgtcgctaat aaggaagcga atcaatacca 480aacctttaat gaagccttga ttgatttgaa aaacgatcga attgatggtc tattgattga 540ccgtgtctat gcaaactatt atttagaagc agaaggtgtt ttaaacgatt ataatgtctt 600tacagttgga ctagaaacag aagcttttgc ggttggagcc cgtaaggaag atacaaactt 660ggttaagaag ataaatgaag ctttttctag tctttacaag gacggcaagt tccaagaaat 720cagccaaaaa tggtttggag aagatgtagc aaccaaagaa gtaaaagaag gacag 77518258PRTStreptococcus pneumoniae 18Gly Lys Asn Ser Ser Glu Thr Ser Gly Asp Asn Trp Ser Lys Tyr Gln1 5 10 15Ser Asn Lys Ser Ile Thr Ile Gly Phe Asp Ser Thr Phe Val Pro Met 20 25 30Gly Phe Ala Gln Lys Asp Gly Ser Tyr Ala Gly Phe Asp Ile Asp Leu 35 40 45Ala Thr Ala Val Phe Glu Lys Tyr Gly Ile Thr Val Asn Trp Gln Pro 50 55 60Ile Asp Trp Asp Leu Lys Glu Ala Glu Leu Thr Lys Gly Thr Ile Asp65 70 75 80Leu Ile Trp Asn Gly Tyr Ser Ala Thr Asp Glu Arg Arg Glu Lys Val 85 90 95Ala Phe Ser Asn Ser Tyr Met Lys Asn Glu Gln Val Leu Val Thr Lys 100 105 110Lys Ser Ser Gly Ile Thr Thr Ala Lys Asp Met Thr Gly Lys Thr Leu 115 120 125Gly Ala Gln Ala Gly Ser Ser Gly Tyr Ala Asp Phe Glu Ala Asn Pro 130 135 140Glu Ile Leu Lys Asn Ile Val Ala Asn Lys Glu Ala Asn Gln Tyr Gln145 150 155 160Thr Phe Asn Glu Ala Leu Ile Asp Leu Lys Asn Asp Arg Ile Asp Gly 165 170 175Leu Leu Ile Asp Arg Val Tyr Ala Asn Tyr Tyr Leu Glu Ala Glu Gly 180 185 190Val Leu Asn Asp Tyr Asn Val Phe Thr Val Gly Leu Glu Thr Glu Ala 195 200 205Phe Ala Val Gly Ala Arg Lys Glu Asp Thr Asn Leu Val Lys Lys Ile 210 215 220Asn Glu Ala Phe Ser Ser Leu Tyr Lys Asp Gly Lys Phe Gln Glu Ile225 230 235 240Ser Gln Lys Trp Phe Gly Glu Asp Val Ala Thr Lys Glu Val Lys Glu 245 250 255Gly Gln19868DNAStreptococcus pneumoniae 19tgctagcgga aaaaaagata caacttctgg tcaaaaacta aaagttgttg ctacaaactc 60aatcatcgct gatattacta aaaatattgc tggtgacaaa attgaccttc atagtatcgt 120tccgattggg caagacccac acgaatacga accacttcct gaagacgtta agaaaacttc 180tgaggctaat ttgattttct ataacggtat caaccttgaa acaggtggca atgcttggtt 240tacaaaattg gtagaaaatg ccaagaaaac tgaaaacaaa gactacttcg cagtcagcga 300cggcgttgat gttatctacc ttgaaggtca aaatgaaaaa ggaaaagaag acccacacgc 360ttggcttaac cttgaaaacg gtattatttt tgctaaaaat atcgccaaac aattgagcgc 420caaagaccct aacaataaag aattctatga aaaaaatctc aaagaatata ctgataagtt 480agacaaactt gataaagaaa gtaaggataa atttaataag atccctgctg aaaagaaact 540cattgtaacc agcgaaggag cattcaaata cttctctaaa gcctatggtg tcccaagtgc 600ttacatctgg gaaatcaata ctgaagaaga aggaactcct gaacaaatca agaccttggt 660tgaaaaactt cgccaaacaa aagttccatc actctttgta gaatcaagtg tggatgaccg 720tccaatgaaa actgtttctc aagacacaaa catcccaatc tacgctcaaa tctttactga 780ctctatcgca gaacaaggta aagaaggcga cagctactac agcatgatga aatacaacct 840tgacaagatt gctgaaggat tggcaaaa 86820289PRTStreptococcus pneumoniae 20Ala Ser Gly Lys Lys Asp Thr Thr Ser Gly Gln Lys Leu Lys Val Val1 5 10 15Ala Thr Asn Ser Ile Ile Ala Asp Ile Thr Lys Asn Ile Ala Gly Asp 20 25 30Lys Ile Asp Leu His Ser Ile Val Pro Ile Gly Gln Asp Pro His Glu 35 40 45Tyr Glu Pro Leu Pro Glu Asp Val Lys Lys Thr Ser Glu Ala Asn Leu 50 55 60Ile Phe Tyr Asn Gly Ile Asn Leu Glu Thr Gly Gly Asn Ala Trp Phe65 70 75 80Thr Lys Leu Val Glu Asn Ala Lys Lys Thr Glu Asn Lys Asp Tyr Phe 85 90 95Ala Val Ser Asp Gly Val Asp Val Ile Tyr Leu Glu Gly Gln Asn Glu 100 105 110Lys Gly Lys Glu Asp Pro His Ala Trp Leu Asn Leu Glu Asn Gly Ile 115 120 125Ile Phe Ala Lys Asn Ile Ala Lys Gln Leu Ser Ala Lys Asp Pro Asn 130 135 140Asn Lys Glu Phe Tyr Glu Lys Asn Leu Lys Glu Tyr Thr Asp Lys Leu145 150 155 160Asp Lys Leu Asp Lys Glu Ser Lys Asp Lys Phe Asn Lys Ile Pro Ala 165 170 175Glu Lys Lys Leu Ile Val Thr Ser Glu Gly Ala Phe Lys Tyr Phe Ser 180 185 190Lys Ala Tyr Gly Val Pro Ser Ala Tyr Ile Trp Glu Ile Asn Thr Glu 195 200 205Glu Glu Gly Thr Pro Glu Gln Ile Lys Thr Leu Val Glu Lys Leu Arg 210 215 220Gln Thr Lys Val Pro Ser Leu Phe Val Glu Ser Ser Val Asp Asp Arg225 230 235 240Pro Met Lys Thr Val Ser Gln Asp Thr Asn Ile Pro Ile Tyr Ala Gln 245 250 255Ile Phe Thr Asp Ser Ile Ala Glu Gln Gly Lys Glu Gly Asp Ser Tyr 260 265 270Tyr Ser Met Met Lys Tyr Asn Leu Asp Lys Ile Ala Glu Gly Leu Ala 275 280 285Lys211546DNAStreptococcus pneumoniae 21tggctcaaaa aatacagctt caagtccaga ttataagttg gaaggtgtaa cattcccgct 60tcaagaaaag aaaacattga agtttatgac agccagttca ccgttatctc ctaaagaccc 120aaatgaaaag ttaattttgc aacgtttgga gaaggaaact ggcgttcata ttgactggac 180caactaccaa tccgactttg cagaaaaacg taacttggat atttctagtg gtgatttacc 240agatgctatc cacaacgacg gagcttcaga tgtggacttg atgaactggg ctaaaaaagg 300tgttattatt ccagttgaag atttgattga taaatacatg ccaaatctta agaaaatttt 360ggatgagaaa ccagagtaca aggccttgat gacagcacct gatgggcaca tttactcatt 420tccatggatt gaagagcttg gagatggtaa agagtctatt cacagtgtca acgatatggc 480ttggattaac aaagattggc ttaagaaact tggtcttgaa atgccaaaaa ctactgatga 540tttgattaaa gtcctagaag ctttcaaaaa cggggatcca aatggaaatg gagaggctga 600tgaaattcca ttttcattta ttagtggtaa cggaaacgaa gattttaaat tcctatttgc 660tgcatttggt ataggggata acgatgatca tttagtagta ggaaatgatg gcaaagttga 720cttcacagca gataacgata actataaaga aggtgtcaaa tttatccgtc aattgcaaga 780aaaaggcctg attgataaag aagctttcga acatgattgg aatagttaca ttgctaaagg 840tcatgatcag aaatttggtg tttactttac atgggataag aataatgtta ctggaagtaa 900cgaaagttat gatgttttac cagtacttgc tggaccaagt ggtcaaaaac acgtagctcg 960tacaaacggt atgggatttg cacgtgacaa gatggttatt accagtgtaa acaaaaacct 1020agaattgaca gctaaatgga ttgatgcaca atacgctcca ctccaatctg tgcaaaataa 1080ctggggaact tacggagatg acaaacaaca aaacatcttt gaattggatc aagcgtcaaa 1140tagtctaaaa cacttaccac taaacggaac tgcaccagca gaacttcgtc aaaagactga 1200agtaggagga ccactagcta tcctagattc atactatggt aaagtaacaa ccatgcctga 1260tgatgccaaa tggcgtttgg atcttatcaa agaatattat gttccttaca tgagcaatgt 1320caataactat ccaagagtct ttatgacaca ggaagatttg gacaagattg cccatatcga 1380agcagatatg aatgactata tctaccgtaa acgtgctgaa tggattgtaa atggcaatat 1440tgatactgag tgggatgatt acaagaaaga acttgaaaaa tacggacttt ctgattacct 1500cgctattaaa caaaaatact acgaccaata ccaagcaaac aaaaac 154622515PRTStreptococcus pneumoniae 22Gly Ser Lys Asn Thr Ala Ser Ser Pro Asp Tyr Lys Leu Glu Gly Val1 5 10 15Thr Phe Pro Leu Gln Glu Lys Lys Thr Leu Lys Phe Met Thr Ala Ser 20 25 30Ser Pro Leu Ser Pro Lys Asp Pro Asn Glu Lys Leu Ile Leu Gln Arg 35 40 45Leu Glu Lys Glu Thr Gly Val His Ile Asp Trp Thr Asn Tyr Gln Ser 50 55 60Asp Phe Ala Glu Lys Arg Asn Leu Asp Ile Ser Ser Gly Asp Leu Pro65 70 75 80Asp Ala Ile His Asn Asp Gly Ala Ser Asp Val Asp Leu Met Asn Trp 85 90 95Ala Lys Lys Gly Val Ile Ile Pro Val Glu Asp Leu Ile Asp Lys Tyr 100 105 110Met Pro Asn Leu Lys Lys Ile Leu Asp Glu Lys Pro Glu Tyr Lys Ala 115 120 125Leu Met Thr Ala Pro Asp Gly His Ile Tyr Ser Phe Pro Trp Ile Glu 130 135 140Glu Leu Gly Asp Gly Lys Glu Ser Ile His Ser Val Asn Asp Met Ala145 150 155 160Trp Ile Asn Lys Asp Trp Leu Lys Lys Leu Gly Leu Glu Met Pro Lys 165 170 175Thr Thr Asp Asp Leu Ile Lys Val Leu Glu Ala Phe Lys Asn Gly Asp 180 185 190Pro Asn Gly Asn Gly Glu Ala Asp Glu Ile Pro Phe Ser Phe Ile Ser 195 200 205Gly Asn Gly Asn Glu Asp Phe Lys Phe Leu Phe Ala Ala Phe Gly Ile 210 215 220Gly Asp Asn Asp Asp His Leu Val Val Gly Asn Asp Gly Lys Val Asp225 230 235 240Phe Thr Ala Asp Asn Asp Asn Tyr Lys Glu Gly Val Lys Phe Ile Arg 245 250 255Gln Leu Gln Glu Lys Gly Leu Ile Asp Lys Glu Ala Phe Glu His Asp 260 265 270Trp Asn Ser Tyr Ile Ala Lys Gly His Asp Gln Lys Phe Gly Val Tyr 275 280 285Phe Thr Trp Asp Lys Asn Asn Val Thr Gly Ser Asn Glu Ser Tyr Asp 290 295 300Val Leu Pro Val Leu Ala Gly Pro Ser Gly Gln Lys His Val Ala Arg305 310 315 320Thr Asn Gly Met Gly Phe Ala Arg Asp Lys Met Val Ile Thr Ser Val 325 330 335Asn Lys Asn Leu Glu Leu Thr Ala Lys Trp Ile Asp Ala Gln Tyr Ala 340 345 350Pro Leu Gln Ser Val Gln Asn Asn Trp Gly Thr Tyr Gly Asp Asp Lys 355 360 365Gln Gln Asn Ile Phe Glu Leu Asp Gln Ala Ser Asn Ser Leu Lys His 370 375 380Leu Pro Leu Asn Gly Thr Ala Pro Ala Glu Leu Arg Gln Lys Thr Glu385 390 395 400Val Gly Gly Pro Leu Ala Ile Leu Asp Ser Tyr Tyr Gly Lys Val Thr 405 410 415Thr Met Pro Asp Asp Ala Lys Trp Arg Leu Asp Leu Ile Lys Glu Tyr 420 425 430Tyr Val Pro Tyr Met Ser Asn Val Asn Asn Tyr Pro Arg Val Phe Met 435 440 445Thr Gln Glu Asp Leu Asp Lys Ile Ala His Ile Glu Ala Asp Met Asn 450 455 460Asp Tyr Ile Tyr Arg Lys Arg Ala Glu Trp Ile Val Asn Gly Asn Ile465 470 475 480Asp Thr Glu Trp Asp Asp Tyr Lys Lys Glu Leu Glu Lys Tyr Gly Leu 485 490 495Ser Asp Tyr Leu Ala Ile Lys Gln Lys Tyr Tyr Asp Gln Tyr Gln Ala 500 505 510Asn Lys Asn 51523895DNAStreptococcus pneumoniae 23tagtacaaac tcaagcacta gtcagacaga gaccagtagc tctgctccaa cagaggtaac 60cattaaaagt tcactggacg aggtcaaact ttccaaagtt cctgaaaaga ttgtgacctt 120tgacctcggc gctgcggata ctattcgcgc tttaggattt gaaaaaaata tcgtcggaat 180gcctacaaaa actgttccga cttatctaaa agacctagtg ggaactgtca aaaatgttgg 240ttctatgaaa gaacctgatt tagaagctat cgccgccctt gagcctgatt tgattatcgc 300ttcgccacgt acacaaaaat tcgtagacaa attcaaagaa atcgccccaa ccgttctctt 360ccaagcaagc aaggacgact actggacttc taccaaggct aatatcgaat ccttagcaag 420tgccttcggc gaaactggta cacagaaagc caaggaagaa ttgaccaagc tagacaagag 480catccaagaa gtcgctacta aaaatgaaag ctctgacaaa aaagcccttg cgatcctcct 540taatgaagga aaaatggcag cctttggtgc caaatctcgt ttctctttct tgtaccaaac 600cttgaaattc aaaccaactg atacaaaatt tgaagactca cgccacggac aagaagtcag 660ctttgaaagt gtcaaagaaa tcaaccctga catcctcttt gtcatcaacc gtacccttgc 720catcggtggg gacaactcta gcaacgacgg tgtcctagaa aatgccctta tcgctgaaac 780acctgctgct aaaaatggta agattatcca actaacacca gacctctggt atctaagcgg 840aggcggactt gaatcaacaa aactcatgat tgaagacata caaaaagctt tgaaa 89524298PRTStreptococcus pneumoniae 24Ser Thr Asn Ser Ser Thr Ser Gln Thr Glu Thr Ser Ser Ser Ala Pro1 5 10 15Thr Glu Val Thr Ile Lys Ser Ser Leu Asp Glu Val Lys Leu Ser Lys 20 25 30Val Pro Glu Lys Ile Val Thr Phe Asp Leu Gly Ala Ala Asp Thr Ile 35 40 45Arg Ala Leu Gly Phe Glu Lys Asn Ile Val Gly Met Pro Thr Lys Thr 50 55 60Val Pro Thr Tyr Leu Lys Asp Leu Val Gly Thr Val Lys Asn Val Gly65 70 75 80Ser Met Lys Glu Pro Asp Leu Glu Ala Ile Ala Ala Leu Glu Pro Asp 85 90 95Leu Ile Ile Ala Ser Pro Arg Thr Gln Lys Phe Val Asp Lys Phe Lys 100 105 110Glu Ile Ala Pro Thr Val Leu Phe Gln Ala Ser Lys Asp Asp Tyr Trp 115 120 125Thr Ser Thr Lys Ala Asn Ile Glu Ser Leu Ala Ser Ala Phe Gly Glu 130 135 140Thr Gly Thr Gln Lys Ala Lys Glu Glu Leu Thr Lys Leu Asp Lys Ser145 150 155 160Ile Gln Glu Val Ala Thr Lys Asn Glu Ser Ser Asp Lys Lys Ala Leu 165 170 175Ala Ile Leu Leu Asn Glu Gly Lys Met Ala Ala Phe Gly Ala Lys Ser 180 185 190Arg Phe Ser Phe Leu Tyr Gln Thr Leu Lys Phe Lys Pro Thr Asp Thr 195 200 205Lys Phe Glu Asp Ser Arg His Gly Gln Glu Val Ser Phe Glu Ser Val 210 215 220Lys Glu Ile Asn Pro Asp Ile Leu Phe Val Ile Asn Arg Thr Leu Ala225 230 235 240Ile Gly Gly Asp Asn Ser Ser Asn Asp Gly Val Leu Glu Asn Ala Leu 245 250 255Ile Ala Glu Thr Pro Ala Ala Lys Asn Gly Lys Ile Ile Gln Leu Thr 260 265 270Pro Asp Leu Trp Tyr Leu Ser Gly Gly Gly Leu Glu Ser Thr Lys Leu 275 280 285Met Ile Glu Asp Ile Gln Lys Ala Leu Lys 290 295251261DNAStreptococcus pneumoniae 25tggcaattct ggcggaagta aagatgctgc caaatcaggt ggtgacggtg ccaaaacaga 60aatcacttgg tgggcattcc cagtatttac ccaagaaaaa actggtgacg gtgttggaac 120ttatgaaaaa tcaatcatcg aagcgtttga aaaagcaaac ccagatataa aagtgaaatt 180ggaaaccatc gacttcaagt caggtcctga aaaaatcaca acagccatcg aagcaggaac 240agctccagac gtactctttg atgcaccagg acgtatcatc caatacggta aaaacggtaa 300attggctgag ttgaatgacc tcttcacaga tgaatttgtt aaagatgtca acaatgaaaa 360catcgtacaa gcaagtaaag ctggagacaa ggcttatatg tatccgatta gttctgcccc 420attctacatg gcaatgaaca agaaaatgtt agaagatgct ggagtagcaa accttgtaaa 480agaaggttgg acaactgatg attttgaaaa agtattgaaa gcacttaaag acaagggtta 540cacaccaggt tcattgttca gttctggtca agggggagac caaggaacac gtgcctttat 600ctctaacctt tatagcggtt ctgtaacaga tgaaaaagtt agcaaatata caactgatga 660tcctaaattc gtcaaaggtc ttgaaaaagc aactagctgg attaaagaca atttgatcaa 720taatggttca caatttgacg gtggggcaga tatccaaaac tttgccaacg gtcaaacatc 780ttacacaatc ctttgggcac cagctcaaaa tggtatccaa gctaaacttt tagaagcaag 840taaggtagaa gtggtagaag taccattccc atcagacgaa ggtaagccag ctcttgagta 900ccttgtaaac gggtttgcag tattcaacaa taaagacgac aagaaagtcg ctgcatctaa 960gaaattcatc cagtttatcg cagatgacaa ggagtgggga cctaaagacg tagttcgtac 1020aggtgctttc ccagtccgta cttcatttgg aaaactttat gaagacaaac gcatggaaac 1080aatcagcggc tggactcaat actactcacc atactacaac actattgatg gatttgctga 1140aatgagaaca ctttggttcc caatgttgca atctgtatca aatggtgacg aaaaaccagc 1200agatgctttg aaagccttca ctgaaaaagc gaacgaaaca atcaaaaaag ctatgaaaca 1260a 126126420PRTStreptococcus pneumoniae 26Gly Asn Ser Gly Gly Ser Lys Asp Ala Ala Lys Ser Gly Gly Asp Gly1 5 10 15Ala Lys Thr Glu Ile Thr Trp Trp Ala Phe Pro Val Phe Thr Gln Glu 20 25 30Lys Thr Gly Asp Gly Val Gly Thr Tyr Glu Lys Ser Ile Ile Glu Ala 35 40 45Phe Glu Lys Ala Asn Pro Asp Ile Lys Val Lys Leu Glu Thr Ile Asp 50 55 60Phe Lys Ser Gly Pro Glu Lys Ile Thr Thr Ala Ile Glu Ala Gly Thr65 70 75 80Ala Pro Asp Val Leu Phe Asp Ala Pro Gly Arg Ile Ile Gln Tyr Gly 85 90 95Lys Asn Gly Lys Leu Ala Glu Leu Asn Asp Leu Phe Thr Asp Glu Phe 100 105 110Val Lys Asp Val Asn Asn Glu Asn Ile Val Gln Ala Ser Lys Ala Gly 115 120 125Asp Lys

Ala Tyr Met Tyr Pro Ile Ser Ser Ala Pro Phe Tyr Met Ala 130 135 140Met Asn Lys Lys Met Leu Glu Asp Ala Gly Val Ala Asn Leu Val Lys145 150 155 160Glu Gly Trp Thr Thr Asp Asp Phe Glu Lys Val Leu Lys Ala Leu Lys 165 170 175Asp Lys Gly Tyr Thr Pro Gly Ser Leu Phe Ser Ser Gly Gln Gly Gly 180 185 190Asp Gln Gly Thr Arg Ala Phe Ile Ser Asn Leu Tyr Ser Gly Ser Val 195 200 205Thr Asp Glu Lys Val Ser Lys Tyr Thr Thr Asp Asp Pro Lys Phe Val 210 215 220Lys Gly Leu Glu Lys Ala Thr Ser Trp Ile Lys Asp Asn Leu Ile Asn225 230 235 240Asn Gly Ser Gln Phe Asp Gly Gly Ala Asp Ile Gln Asn Phe Ala Asn 245 250 255Gly Gln Thr Ser Tyr Thr Ile Leu Trp Ala Pro Ala Gln Asn Gly Ile 260 265 270Gln Ala Lys Leu Leu Glu Ala Ser Lys Val Glu Val Val Glu Val Pro 275 280 285Phe Pro Ser Asp Glu Gly Lys Pro Ala Leu Glu Tyr Leu Val Asn Gly 290 295 300Phe Ala Val Phe Asn Asn Lys Asp Asp Lys Lys Val Ala Ala Ser Lys305 310 315 320Lys Phe Ile Gln Phe Ile Ala Asp Asp Lys Glu Trp Gly Pro Lys Asp 325 330 335Val Val Arg Thr Gly Ala Phe Pro Val Arg Thr Ser Phe Gly Lys Leu 340 345 350Tyr Glu Asp Lys Arg Met Glu Thr Ile Ser Gly Trp Thr Gln Tyr Tyr 355 360 365Ser Pro Tyr Tyr Asn Thr Ile Asp Gly Phe Ala Glu Met Arg Thr Leu 370 375 380Trp Phe Pro Met Leu Gln Ser Val Ser Asn Gly Asp Glu Lys Pro Ala385 390 395 400Asp Ala Leu Lys Ala Phe Thr Glu Lys Ala Asn Glu Thr Ile Lys Lys 405 410 415Ala Met Lys Gln 42027658DNAStreptococcus pneumoniae 27ttcacaagaa aaaacaaaaa atgaagatgg agaaactaag acagaacaga cagccaaagc 60tgatggaaca gtcggtagta agtctcaagg agctgcccag aagaaagcag aagtggtcaa 120taaaggtgat tactacagca ttcaagggaa atacgatgaa atcatcgtag ccaacaaaca 180ctatccattg tctaaagact ataatccagg ggaaaatcca acagccaagg cagagttggt 240caaactcatc aaagcgatgc aagaggcagg tttccctatt agtgatcatt acagtggttt 300tagaagttat gaaactcaga ccaagctcta tcaagattat gtcaaccaag atggaaaggc 360agcagctgac cgttactctg cccgtcctgg ctatagcgaa caccagacag gcttggcctt 420tgatgtgatt gggactgatg gtgatttggt gacagaagaa aaagcagccc aatggctctt 480ggatcatgca gctgattatg gctttgttgt ccgttatctc aaaggcaagg aaaaggaaac 540aggctatatg gctgaagaat ggcacctgcg ttatgtagga aaagaagcta aagaaattgc 600tgcaagtggt ctcagtttgg aagaatacta tggctttgaa ggcggagact acgtcgat 65828219PRTStreptococcus pneumoniae 28Ser Gln Glu Lys Thr Lys Asn Glu Asp Gly Glu Thr Lys Thr Glu Gln1 5 10 15Thr Ala Lys Ala Asp Gly Thr Val Gly Ser Lys Ser Gln Gly Ala Ala 20 25 30Gln Lys Lys Ala Glu Val Val Asn Lys Gly Asp Tyr Tyr Ser Ile Gln 35 40 45Gly Lys Tyr Asp Glu Ile Ile Val Ala Asn Lys His Tyr Pro Leu Ser 50 55 60Lys Asp Tyr Asn Pro Gly Glu Asn Pro Thr Ala Lys Ala Glu Leu Val65 70 75 80Lys Leu Ile Lys Ala Met Gln Glu Ala Gly Phe Pro Ile Ser Asp His 85 90 95Tyr Ser Gly Phe Arg Ser Tyr Glu Thr Gln Thr Lys Leu Tyr Gln Asp 100 105 110Tyr Val Asn Gln Asp Gly Lys Ala Ala Ala Asp Arg Tyr Ser Ala Arg 115 120 125Pro Gly Tyr Ser Glu His Gln Thr Gly Leu Ala Phe Asp Val Ile Gly 130 135 140Thr Asp Gly Asp Leu Val Thr Glu Glu Lys Ala Ala Gln Trp Leu Leu145 150 155 160Asp His Ala Ala Asp Tyr Gly Phe Val Val Arg Tyr Leu Lys Gly Lys 165 170 175Glu Lys Glu Thr Gly Tyr Met Ala Glu Glu Trp His Leu Arg Tyr Val 180 185 190Gly Lys Glu Ala Lys Glu Ile Ala Ala Ser Gly Leu Ser Leu Glu Glu 195 200 205Tyr Tyr Gly Phe Glu Gly Gly Asp Tyr Val Asp 210 21529790DNAStreptococcus pneumoniae 29gaaaggtctg tggtcaaata atcttacctg cggttatgat gaaaaaataa tcttggaaaa 60tataaatata aaaatacctg aagaaaaaat atcagttatt attgggtcaa atggttgtgg 120gaaatcaaca ctcattaaaa ccttgtctcg acttataaag ccattagagg gagaagtatt 180gcttgataat aaatcaatta attcttataa agaaaaagat ttagcaaaac acatagctat 240attacctcaa tctccaataa tccctgaatc aataacagta gctgatcttg taagccgtgg 300tcgtttcccc tacagaaagc cttttaagag tcttggaaaa gatgaccttg aaataataaa 360cagatcaatg gttaaggcca atgttgaaga tctagcaaat aacctagttg aagaactttc 420tgggggtcaa aggcaaagag tatggatagc tctagcccta gcccaagata caagtatcct 480acttttagat gagccaacta cttacttgga tatctcatat caaatagaac tattagacct 540cttgactgat ctaaaccaaa aatataagac aaccatttgc atgattttgc acgatataaa 600tctaacagca agatacgctg attacctatt tgcaattaaa gaaggtaaac ttgttgcaga 660gggaaagcct gaagatatac taaatgataa actagttaaa gatatcttta atcttgaagc 720aaaaattata cgtgacccta tttccaattc gcctctaatg attcctattg gcaagcacca 780tgttaactct 79030262PRTStreptococcus pneumoniae 30Lys Gly Leu Trp Ser Asn Asn Leu Thr Cys Gly Tyr Asp Glu Lys Ile1 5 10 15Ile Leu Glu Asn Ile Asn Ile Lys Ile Pro Glu Glu Lys Ile Ser Val 20 25 30Ile Ile Gly Ser Asn Gly Cys Gly Lys Ser Thr Leu Ile Lys Thr Leu 35 40 45Ser Arg Leu Ile Lys Pro Leu Glu Gly Glu Val Leu Leu Asp Asn Lys 50 55 60Ser Ile Asn Ser Tyr Lys Glu Lys Asp Leu Ala Lys His Ile Ala Ile65 70 75 80Leu Pro Gln Ser Pro Ile Ile Pro Glu Ser Ile Thr Val Ala Asp Leu 85 90 95Val Ser Arg Gly Arg Phe Pro Tyr Arg Lys Pro Phe Lys Ser Leu Gly 100 105 110Lys Asp Asp Leu Glu Ile Ile Asn Arg Ser Met Val Lys Ala Asn Val 115 120 125Glu Asp Leu Ala Asn Asn Leu Val Glu Glu Leu Ser Gly Gly Gln Arg 130 135 140Gln Arg Val Trp Ile Ala Leu Ala Leu Ala Gln Asp Thr Ser Ile Leu145 150 155 160Leu Leu Asp Glu Pro Thr Thr Tyr Leu Asp Ile Ser Tyr Gln Ile Glu 165 170 175Leu Leu Asp Leu Leu Thr Asp Leu Asn Gln Lys Tyr Lys Thr Thr Ile 180 185 190Cys Met Ile Leu His Asp Ile Asn Leu Thr Ala Arg Tyr Ala Asp Tyr 195 200 205Leu Phe Ala Ile Lys Glu Gly Lys Leu Val Ala Glu Gly Lys Pro Glu 210 215 220Asp Ile Leu Asn Asp Lys Leu Val Lys Asp Ile Phe Asn Leu Glu Ala225 230 235 240Lys Ile Ile Arg Asp Pro Ile Ser Asn Ser Pro Leu Met Ile Pro Ile 245 250 255Gly Lys His His Val Ser 26031781DNAStreptococcus pneumoniae 31aaactcagaa aagaaagcag acaatgcaac aactatcaaa atcgcaactg ttaaccgtag 60cggttctgaa gaaaaacgtt gggacaaaat ccaagaattg gttaaaaaag acggaattac 120cttggaattt acagagttca cagactactc acaaccaaac aaagcaactg ctgatggcga 180agtagatttg aacgctttcc aacactataa cttcttgaac aactggaaca aagaaaacgg 240aaaagacctt gtagcgattg cagatactta catctctcca atccgccttt actcaggttt 300gaatggaagt gccaacaagt acactaaagt agaagacatc ccagcaaacg gagaaatcgc 360tgtaccgaat gacgctacaa acgaaagccg tgcgctttat ttgcttcaat cagctggctt 420gattaaattg gatgtttctg gaactgctct tgcaacagtt gccaacatca aagaaaatcc 480aaagaacttg aaaatcactg aattggacgc tagccaaaca gctcgttcat tgtcatcagt 540tgacgctgcc gttgtaaaca ataccttcgt tacagaagca aaattggact acaagaaatc 600acttttcaaa gaacaagctg atgaaaactc aaaacaatgg tacaacatca ttgttgcaaa 660aaaagattgg gaaacatcac ctaaggctga tgctatcaag aaagtaatcg cagcttacca 720cacagatgac gtgaaaaaag ttatcgaaga atcatcagat ggtttggatc aaccagtttg 780g 78132260PRTStreptococcus pneumoniae 32Asn Ser Glu Lys Lys Ala Asp Asn Ala Thr Thr Ile Lys Ile Ala Thr1 5 10 15Val Asn Arg Ser Gly Ser Glu Glu Lys Arg Trp Asp Lys Ile Gln Glu 20 25 30Leu Val Lys Lys Asp Gly Ile Thr Leu Glu Phe Thr Glu Phe Thr Asp 35 40 45Tyr Ser Gln Pro Asn Lys Ala Thr Ala Asp Gly Glu Val Asp Leu Asn 50 55 60Ala Phe Gln His Tyr Asn Phe Leu Asn Asn Trp Asn Lys Glu Asn Gly65 70 75 80Lys Asp Leu Val Ala Ile Ala Asp Thr Tyr Ile Ser Pro Ile Arg Leu 85 90 95Tyr Ser Gly Leu Asn Gly Ser Ala Asn Lys Tyr Thr Lys Val Glu Asp 100 105 110Ile Pro Ala Asn Gly Glu Ile Ala Val Pro Asn Asp Ala Thr Asn Glu 115 120 125Ser Arg Ala Leu Tyr Leu Leu Gln Ser Ala Gly Leu Ile Lys Leu Asp 130 135 140Val Ser Gly Thr Ala Leu Ala Thr Val Ala Asn Ile Lys Glu Asn Pro145 150 155 160Lys Asn Leu Lys Ile Thr Glu Leu Asp Ala Ser Gln Thr Ala Arg Ser 165 170 175Leu Ser Ser Val Asp Ala Ala Val Val Asn Asn Thr Phe Val Thr Glu 180 185 190Ala Lys Leu Asp Tyr Lys Lys Ser Leu Phe Lys Glu Gln Ala Asp Glu 195 200 205Asn Ser Lys Gln Trp Tyr Asn Ile Ile Val Ala Lys Lys Asp Trp Glu 210 215 220Thr Ser Pro Lys Ala Asp Ala Ile Lys Lys Val Ile Ala Ala Tyr His225 230 235 240Thr Asp Asp Val Lys Lys Val Ile Glu Glu Ser Ser Asp Gly Leu Asp 245 250 255Gln Pro Val Trp 26033640DNAStreptococcus pneumoniae 33ttcgaaaggg tcagaaggtg cagaccttat cagcatgaaa ggggatgtca ttacagaaca 60tcaattttat gagcaagtga aaagcaaccc ttcagcccaa caagtcttgt taaatatgac 120catccaaaaa gtttttgaaa aacaatatgg ctcagagctt gatgataaag aggttgatga 180tactattgcc gaagaaaaaa aacaatatgg cgaaaactac caacgtgtct tgtcacaagc 240aggtatgact cttgaaacac gtaaagctca aattcgtaca agtaaattag ttgagttggc 300agttaagaag gtagcagaag ctgaattgac agatgaagcc tataagaaag cctttgatga 360gtacactcca gatgtaacgg ctcaaatcat ccgtcttaat aatgaagata aggccaaaga 420agttctcgaa aaagccaagg cagaaggtgc tgattttgct caattagcca aagataattc 480aactgatgaa aaaacaaaag aaaatggtgg agaaattacc tttgattctg cttcaacaga 540agtacctgga gcaagtccaa aaaagccgct tttcgctttt agatgtggga tggtgtttct 600ggatgtggat tacagcaact ggggcacacc aagcctacag 64034213PRTStreptococcus pneumoniae 34Ser Lys Gly Ser Glu Gly Ala Asp Leu Ile Ser Met Lys Gly Asp Val1 5 10 15Ile Thr Glu His Gln Phe Tyr Glu Gln Val Lys Ser Asn Pro Ser Ala 20 25 30Gln Gln Val Leu Leu Asn Met Thr Ile Gln Lys Val Phe Glu Lys Gln 35 40 45Tyr Gly Ser Glu Leu Asp Asp Lys Glu Val Asp Asp Thr Ile Ala Glu 50 55 60Glu Lys Lys Gln Tyr Gly Glu Asn Tyr Gln Arg Val Leu Ser Gln Ala65 70 75 80Gly Met Thr Leu Glu Thr Arg Lys Ala Gln Ile Arg Thr Ser Lys Leu 85 90 95Val Glu Leu Ala Val Lys Lys Val Ala Glu Ala Glu Leu Thr Asp Glu 100 105 110Ala Tyr Lys Lys Ala Phe Asp Glu Tyr Thr Pro Asp Val Thr Ala Gln 115 120 125Ile Ile Arg Leu Asn Asn Glu Asp Lys Ala Lys Glu Val Leu Glu Lys 130 135 140Ala Lys Ala Glu Gly Ala Asp Phe Ala Gln Leu Ala Lys Asp Asn Ser145 150 155 160Thr Asp Glu Lys Thr Lys Glu Asn Gly Gly Glu Ile Thr Phe Asp Ser 165 170 175Ala Ser Thr Glu Val Pro Gly Ala Ser Pro Lys Lys Pro Leu Phe Ala 180 185 190Phe Arg Cys Gly Met Val Phe Leu Asp Val Asp Tyr Ser Asn Trp Gly 195 200 205Thr Pro Ser Leu Gln 21035631DNAStreptococcus pneumoniae 35ggggatggca gcttttaaaa atcctaacaa tcaatacaaa gctattacaa ttgctcaaac 60tctaggtgat gatgcttctt cagaggaatt ggctggtaga tatggttctg ctgttcagtg 120tacagaagtg actgcctcaa acctttcaac agttaaaact aaagctacgg ttgtagaaaa 180accactgaaa gattttagag cgtctacgtc tgatcagtct ggttgggtgg aatctaatgg 240taaatggtat ttctatgagt ctggtgatgt gaagacaggt tgggtgaaaa cagatggtaa 300atggtactat ttgaatgact taggtgtcat gcagactgga tttgtaaaat tttctggtag 360ctggtattac ttgagcaatt caggtgctat gtttacaggc tggggaacag atggtagcag 420atggttctac tttgacggct caggagctat gaagacaggc tggtacaagg aaaatggcac 480ttggtattac cttgacgaag caggtatcat gaagacaggt tggtttaaag tcggaccaca 540ctggtactat gcctacggtt caggagcttt ggctgtgagc acaacaacac cagatggtta 600ccgtgtaaat ggtaatggtg aatgggtaaa c 63136210PRTStreptococcus pneumoniae 36Gly Met Ala Ala Phe Lys Asn Pro Asn Asn Gln Tyr Lys Ala Ile Thr1 5 10 15Ile Ala Gln Thr Leu Gly Asp Asp Ala Ser Ser Glu Glu Leu Ala Gly 20 25 30Arg Tyr Gly Ser Ala Val Gln Cys Thr Glu Val Thr Ala Ser Asn Leu 35 40 45Ser Thr Val Lys Thr Lys Ala Thr Val Val Glu Lys Pro Leu Lys Asp 50 55 60Phe Arg Ala Ser Thr Ser Asp Gln Ser Gly Trp Val Glu Ser Asn Gly65 70 75 80Lys Trp Tyr Phe Tyr Glu Ser Gly Asp Val Lys Thr Gly Trp Val Lys 85 90 95Thr Asp Gly Lys Trp Tyr Tyr Leu Asn Asp Leu Gly Val Met Gln Thr 100 105 110Gly Phe Val Lys Phe Ser Gly Ser Trp Tyr Tyr Leu Ser Asn Ser Gly 115 120 125Ala Met Phe Thr Gly Trp Gly Thr Asp Gly Ser Arg Trp Phe Tyr Phe 130 135 140Asp Gly Ser Gly Ala Met Lys Thr Gly Trp Tyr Lys Glu Asn Gly Thr145 150 155 160Trp Tyr Tyr Leu Asp Glu Ala Gly Ile Met Lys Thr Gly Trp Phe Lys 165 170 175Val Gly Pro His Trp Tyr Tyr Ala Tyr Gly Ser Gly Ala Leu Ala Val 180 185 190Ser Thr Thr Thr Pro Asp Gly Tyr Arg Val Asn Gly Asn Gly Glu Trp 195 200 205Val Asn 210371360DNAStreptococcus pneumoniae 37agacgagcaa aaaattaagc aagcagaagc ggaagttgag agtaaacaag ctgaggctac 60aaggttaaaa aaaatcaaga cagatcgtga agaagcagaa gaagaagcta aacgaagagc 120agatgctaaa gagcaaggta aaccaaaggg gcgggcaaaa cgaggagttc ctggagagct 180agcaacacct gataaaaaag aaaatgatgc gaagtcttca gattctagcg taggtgaaga 240aactcttcca agcccatccc tgaaaccaga aaaaaaggta gcagaagctg agaagaaggt 300tgaagaagct aagaaaaaag ccgaggatca aaaagaagaa gatcgccgta actacccaac 360caatacttac aaaacgcttg aacttgaaat tgctgagtcc gatgtggaag ttaaaaaagc 420ggagcttgaa ctagtaaaag aggaagctaa ggaacctcga aacgaggaaa aagttaagca 480agcaaaagcg gaagttgaga gtaaaaaagc tgaggctaca aggttagaaa aaatcaagac 540agatcgtaaa aaagcagaag aagaagctaa acgaaaagca gcagaagaag ataaagttaa 600agaaaaacca gctgaacaac cacaaccagc gccggctcca aaagcagaaa aaccagctcc 660agctccaaaa ccagagaatc cagctgaaca accaaaagca gaaaaaccag ctgatcaaca 720agctgaagaa gactatgctc gtagatcaga agaagaatat aatcgcttga ctcaacagca 780accgccaaaa actgaaaaac cagcacaacc atctactcca aaaacaggct ggaaacaaga 840aaacggtatg tggtacttct acaatactga tggttcaatg gcgacaggat ggctccaaaa 900caatggctca tggtactacc tcaacagcaa tggcgctatg gcgacaggat ggctccaaaa 960caatggttca tggtactatc taaacgctaa tggttcaatg gcaacaggat ggctccaaaa 1020caatggttca tggtactacc taaacgctaa tggttcaatg gcgacaggat ggctccaata 1080caatggctca tggtactacc taaacgctaa tggttcaatg gcgacaggat ggctccaata 1140caatggctca tggtactacc taaacgctaa tggtgatatg gcgacaggtt gggtgaaaga 1200tggagatacc tggtactatc ttgaagcatc aggtgctatg aaagcaagcc aatggttcaa 1260agtatcagat aaatggtact atgtcaatgg ctcaggtgcc cttgcagtca acacaactgt 1320agatggctat ggagtcaatg ccaatggtga atgggtaaac 136038453PRTStreptococcus pneumoniae 38Asp Glu Gln Lys Ile Lys Gln Ala Glu Ala Glu Val Glu Ser Lys Gln1 5 10 15Ala Glu Ala Thr Arg Leu Lys Lys Ile Lys Thr Asp Arg Glu Glu Ala 20 25 30Glu Glu Glu Ala Lys Arg Arg Ala Asp Ala Lys Glu Gln Gly Lys Pro 35 40 45Lys Gly Arg Ala Lys Arg Gly Val Pro Gly Glu Leu Ala Thr Pro Asp 50 55 60Lys Lys Glu Asn Asp Ala Lys Ser Ser Asp Ser Ser Val Gly Glu Glu65 70 75 80Thr Leu Pro Ser Pro Ser Leu Lys Pro Glu Lys Lys Val Ala Glu Ala 85 90 95Glu Lys Lys Val Glu Glu Ala Lys Lys Lys Ala Glu Asp Gln Lys Glu 100 105 110Glu Asp Arg Arg Asn Tyr Pro Thr Asn Thr Tyr Lys Thr Leu Glu Leu 115 120 125Glu Ile Ala Glu Ser Asp Val Glu Val Lys Lys Ala Glu Leu Glu Leu

130 135 140Val Lys Glu Glu Ala Lys Glu Pro Arg Asn Glu Glu Lys Val Lys Gln145 150 155 160Ala Lys Ala Glu Val Glu Ser Lys Lys Ala Glu Ala Thr Arg Leu Glu 165 170 175Lys Ile Lys Thr Asp Arg Lys Lys Ala Glu Glu Glu Ala Lys Arg Lys 180 185 190Ala Ala Glu Glu Asp Lys Val Lys Glu Lys Pro Ala Glu Gln Pro Gln 195 200 205Pro Ala Pro Ala Pro Lys Ala Glu Lys Pro Ala Pro Ala Pro Lys Pro 210 215 220Glu Asn Pro Ala Glu Gln Pro Lys Ala Glu Lys Pro Ala Asp Gln Gln225 230 235 240Ala Glu Glu Asp Tyr Ala Arg Arg Ser Glu Glu Glu Tyr Asn Arg Leu 245 250 255Thr Gln Gln Gln Pro Pro Lys Thr Glu Lys Pro Ala Gln Pro Ser Thr 260 265 270Pro Lys Thr Gly Trp Lys Gln Glu Asn Gly Met Trp Tyr Phe Tyr Asn 275 280 285Thr Asp Gly Ser Met Ala Thr Gly Trp Leu Gln Asn Asn Gly Ser Trp 290 295 300Tyr Tyr Leu Asn Ser Asn Gly Ala Met Ala Thr Gly Trp Leu Gln Asn305 310 315 320Asn Gly Ser Trp Tyr Tyr Leu Asn Ala Asn Gly Ser Met Ala Thr Gly 325 330 335Trp Leu Gln Asn Asn Gly Ser Trp Tyr Tyr Leu Asn Ala Asn Gly Ser 340 345 350Met Ala Thr Gly Trp Leu Gln Tyr Asn Gly Ser Trp Tyr Tyr Leu Asn 355 360 365Ala Asn Gly Ser Met Ala Thr Gly Trp Leu Gln Tyr Asn Gly Ser Trp 370 375 380Tyr Tyr Leu Asn Ala Asn Gly Asp Met Ala Thr Gly Trp Val Lys Asp385 390 395 400Gly Asp Thr Trp Tyr Tyr Leu Glu Ala Ser Gly Ala Met Lys Ala Ser 405 410 415Gln Trp Phe Lys Val Ser Asp Lys Trp Tyr Tyr Val Asn Gly Ser Gly 420 425 430Ala Leu Ala Val Asn Thr Thr Val Asp Gly Tyr Gly Val Asn Ala Asn 435 440 445Gly Glu Trp Val Asn 45039412DNAStreptococcus pneumoniae 39ctgtggtgag gaagaaacta aaaagactca agcagcacaa cagccaaaac aacaaacgac 60tgtacaacaa attgctgttg gaaaagatgc tccagacttc acattgcaat ccatggatgg 120caaagaagtt aagttatctg attttaaggg taaaaaggtt tacttgaagt tttgggcttc 180atggtgtggt ccatgcaaga aaagtatgcc agagttgatg gaactagcgg cgaaaccaga 240tcgtgatttc gaaattctta ctgtcattgc accaggaatt caaggtgaaa aaactgttga 300gcaattccca caatggttcc aggaacaagg atataaggat atcccagttc tttatgatac 360caaagcaacc acttccaagc ttatcaaatt cgaagcattc ctacagaata tt 41240137PRTStreptococcus pneumoniae 40Cys Gly Glu Glu Glu Thr Lys Lys Thr Gln Ala Ala Gln Gln Pro Lys1 5 10 15Gln Gln Thr Thr Val Gln Gln Ile Ala Val Gly Lys Asp Ala Pro Asp 20 25 30Phe Thr Leu Gln Ser Met Asp Gly Lys Glu Val Lys Leu Ser Asp Phe 35 40 45Lys Gly Lys Lys Val Tyr Leu Lys Phe Trp Ala Ser Trp Cys Gly Pro 50 55 60Cys Lys Lys Ser Met Pro Glu Leu Met Glu Leu Ala Ala Lys Pro Asp65 70 75 80Arg Asp Phe Glu Ile Leu Thr Val Ile Ala Pro Gly Ile Gln Gly Glu 85 90 95Lys Thr Val Glu Gln Phe Pro Gln Trp Phe Gln Glu Gln Gly Tyr Lys 100 105 110Asp Ile Pro Val Leu Tyr Asp Thr Lys Ala Thr Thr Ser Lys Leu Ile 115 120 125Lys Phe Glu Ala Phe Leu Gln Asn Ile 130 135411462DNAStreptococcus pneumoniae 41gacttttaac aataaaacta ttgaagagtt gcacaatctc cttgtctcta aggaaatttc 60tgcaacagaa ttgacccaag caacacttga aaatatcaag tctcgtgagg aagccctcaa 120ttcatttgtc accatcgctg aggagcaagc tcttgttcaa gctaaagcca ttgatgaagc 180tggaattgat gctgacaatg tcctttcagg aattccactt gctgttaagg ataacatctc 240tacagacggt attctcacaa ctgctgcctc aaaaatgctc tacaactatg agccaatctt 300tgatgcgaca gctgttgcca atgcaaaaac caagggcatg attgtcgttg gaaagaccaa 360catggacgaa tttgctatgg gtggttcagg tgaaacttca cactacggag caactaaaaa 420cgcttggaac cacagcaagg ttcctggtgg gtcatcaagt ggttctgccg cagctgtagc 480ctcaggacaa gttcgcttgt cacttggttc tgatactggt ggttccatcc gccaacctgc 540tgccttcaac ggaatcgttg gtctcaaacc aacctacgga acagtttcac gtttcggtct 600cattgccttt ggtagctcat tagaccagat tggacctttt gctcctactg ttaaggaaaa 660tgccctcttg ctcaacgcta ttgccagcga agatgctaaa gactctactt ctgctcctgt 720ccgcatcgcc gactttactt caaaaatcgg ccaagacatc aagggtatga aaatcgcttt 780gcctaaggaa tacctaggcg aaggaattga tccagaggtt aaggaaacaa tcttaaacgc 840ggccaaacac tttgaaaaat tgggtgctat cgtcgaagaa gtcagccttc ctcactctaa 900atacggtgtt gccgtttatt acatcatcgc ttcatcagaa gcttcatcaa acttgcaacg 960cttcgacggt atccgttacg gctatcgcgc agaagatgca accaaccttg atgaaatcta 1020tgtaaacagc cgaagccaag gttttggtga agaggtaaaa cgtcgtatca tgctgggtac 1080tttcagtctt tcatcaggtt actatgatgc ctactacaaa aaggctggtc aagtccgtac 1140cctcatcatt caagatttcg aaaaagtctt cgcggattac gatttgattt tgggtccaac 1200tgctccaagt gttgcctatg acttggattc tctcaaccat gacccagttg ccatgtactt 1260agccgaccta ttgaccatac ctgtaaactt ggcaggactg cctggaattt cgattcctgc 1320tggattctct caaggtctac ctgtcggact ccaattgatt ggtcccaagt actctgagga 1380aaccatttac caagctgctg ctgcttttga agcaacaaca gactaccaca aacaacaacc 1440cgtgattttt ggaggtgaca ac 146242487PRTStreptococcus pneumoniae 42Thr Phe Asn Asn Lys Thr Ile Glu Glu Leu His Asn Leu Leu Val Ser1 5 10 15Lys Glu Ile Ser Ala Thr Glu Leu Thr Gln Ala Thr Leu Glu Asn Ile 20 25 30Lys Ser Arg Glu Glu Ala Leu Asn Ser Phe Val Thr Ile Ala Glu Glu 35 40 45Gln Ala Leu Val Gln Ala Lys Ala Ile Asp Glu Ala Gly Ile Asp Ala 50 55 60Asp Asn Val Leu Ser Gly Ile Pro Leu Ala Val Lys Asp Asn Ile Ser65 70 75 80Thr Asp Gly Ile Leu Thr Thr Ala Ala Ser Lys Met Leu Tyr Asn Tyr 85 90 95Glu Pro Ile Phe Asp Ala Thr Ala Val Ala Asn Ala Lys Thr Lys Gly 100 105 110Met Ile Val Val Gly Lys Thr Asn Met Asp Glu Phe Ala Met Gly Gly 115 120 125Ser Gly Glu Thr Ser His Tyr Gly Ala Thr Lys Asn Ala Trp Asn His 130 135 140Ser Lys Val Pro Gly Gly Ser Ser Ser Gly Ser Ala Ala Ala Val Ala145 150 155 160Ser Gly Gln Val Arg Leu Ser Leu Gly Ser Asp Thr Gly Gly Ser Ile 165 170 175Arg Gln Pro Ala Ala Phe Asn Gly Ile Val Gly Leu Lys Pro Thr Tyr 180 185 190Gly Thr Val Ser Arg Phe Gly Leu Ile Ala Phe Gly Ser Ser Leu Asp 195 200 205Gln Ile Gly Pro Phe Ala Pro Thr Val Lys Glu Asn Ala Leu Leu Leu 210 215 220Asn Ala Ile Ala Ser Glu Asp Ala Lys Asp Ser Thr Ser Ala Pro Val225 230 235 240Arg Ile Ala Asp Phe Thr Ser Lys Ile Gly Gln Asp Ile Lys Gly Met 245 250 255Lys Ile Ala Leu Pro Lys Glu Tyr Leu Gly Glu Gly Ile Asp Pro Glu 260 265 270Val Lys Glu Thr Ile Leu Asn Ala Ala Lys His Phe Glu Lys Leu Gly 275 280 285Ala Ile Val Glu Glu Val Ser Leu Pro His Ser Lys Tyr Gly Val Ala 290 295 300Val Tyr Tyr Ile Ile Ala Ser Ser Glu Ala Ser Ser Asn Leu Gln Arg305 310 315 320Phe Asp Gly Ile Arg Tyr Gly Tyr Arg Ala Glu Asp Ala Thr Asn Leu 325 330 335Asp Glu Ile Tyr Val Asn Ser Arg Ser Gln Gly Phe Gly Glu Glu Val 340 345 350Lys Arg Arg Ile Met Leu Gly Thr Phe Ser Leu Ser Ser Gly Tyr Tyr 355 360 365Asp Ala Tyr Tyr Lys Lys Ala Gly Gln Val Arg Thr Leu Ile Ile Gln 370 375 380Asp Phe Glu Lys Val Phe Ala Asp Tyr Asp Leu Ile Leu Gly Pro Thr385 390 395 400Ala Pro Ser Val Ala Tyr Asp Leu Asp Ser Leu Asn His Asp Pro Val 405 410 415Ala Met Tyr Leu Ala Asp Leu Leu Thr Ile Pro Val Asn Leu Ala Gly 420 425 430Leu Pro Gly Ile Ser Ile Pro Ala Gly Phe Ser Gln Gly Leu Pro Val 435 440 445Gly Leu Gln Leu Ile Gly Pro Lys Tyr Ser Glu Glu Thr Ile Tyr Gln 450 455 460Ala Ala Ala Ala Phe Glu Ala Thr Thr Asp Tyr His Lys Gln Gln Pro465 470 475 480Val Ile Phe Gly Gly Asp Asn 48543433DNAStreptococcus pneumoniae 43ctttacaggt aaacaactac aagtcggcga caaggcgctt gatttttctc ttactacaac 60agatctttct aaaaaatctc tggctgattt tgatggcaag aaaaaagtct tgagtgtcgt 120tccttctatc gatacaggca tctgctcaac tcaaacacgt cgttttaatg aagaattggc 180tggactggac aacacggtcg tattgactgt ttcaatggac ctaccttttg ctcaaaaacg 240ttggtgcggt gctgaaggcc ttgacaatgc cattatgctt tcagactact ttgaccattc 300tttcgggcgc gattatgccc tcttgatcaa cgaatggcac ctattagcac gcgcagtctt 360tgtcctcgat actgacaata cgattcgcta cgttgaatac gtggataata tcaattctga 420gccaaacttc gaa 43344144PRTStreptococcus pneumoniae 44Phe Thr Gly Lys Gln Leu Gln Val Gly Asp Lys Ala Leu Asp Phe Ser1 5 10 15Leu Thr Thr Thr Asp Leu Ser Lys Lys Ser Leu Ala Asp Phe Asp Gly 20 25 30Lys Lys Lys Val Leu Ser Val Val Pro Ser Ile Asp Thr Gly Ile Cys 35 40 45Ser Thr Gln Thr Arg Arg Phe Asn Glu Glu Leu Ala Gly Leu Asp Asn 50 55 60Thr Val Val Leu Thr Val Ser Met Asp Leu Pro Phe Ala Gln Lys Arg65 70 75 80Trp Cys Gly Ala Glu Gly Leu Asp Asn Ala Ile Met Leu Ser Asp Tyr 85 90 95Phe Asp His Ser Phe Gly Arg Asp Tyr Ala Leu Leu Ile Asn Glu Trp 100 105 110His Leu Leu Ala Arg Ala Val Phe Val Leu Asp Thr Asp Asn Thr Ile 115 120 125Arg Tyr Val Glu Tyr Val Asp Asn Ile Asn Ser Glu Pro Asn Phe Glu 130 135 14045724DNAStreptococcus pneumoniaemisc_feature(88)..(88)n is a, c, g, or t 45ccaggctgat acaagtatcg cagacattca aaaaagaggc gaactggttg tcggtgtcaa 60acaagacgtt cccaattttg gttacaanga tcccaagacc ggtacttatt ctggtatcga 120aaccgacttg gccaagatgg tagctgatga actcaaggtc aagattcgct atgtgccggt 180tacagcacaa acccgcggcc cccttctaga caatgaacag gtcgatatgg atatcgcgac 240ctttaccatc acggacgaac gcaaaaaact ctacaacttt accagtccct actacacaga 300cgcttctgga tttttggtca ataaatctgc caaaatcaaa aagattgagg acctaaacgg 360caaaaccatc ggagtcgccc aaggttctat cacccaacgc ctgattactg aactgggtaa 420aaagaaaggt ctgaagttta aattcgtcga acttggttcc tacccagaat tgattacttc 480cctgcacgct catcgtatcg ataccttttc cgttgaccgc tctattctat ctggctacac 540tagtaaacgg acagcactac tagatgatag tttcaagcca tctgactacg gtattgttac 600caagaaatca aatacagagc tcaacgacta tcttgataac ttggttacta aatggagcaa 660ggatggtagt ttgcagaaac tttatgaccg ttacaagctc aaaccatcta gccatactgc 720agat 72446241PRTStreptococcus pneumoniaeSITE(29)..(29)Xaa can be any naturally occurring amino acid 46Gln Ala Asp Thr Ser Ile Ala Asp Ile Gln Lys Arg Gly Glu Leu Val1 5 10 15Val Gly Val Lys Gln Asp Val Pro Asn Phe Gly Tyr Xaa Asp Pro Lys 20 25 30Thr Gly Thr Tyr Ser Gly Ile Glu Thr Asp Leu Ala Lys Met Val Ala 35 40 45Asp Glu Leu Lys Val Lys Ile Arg Tyr Val Pro Val Thr Ala Gln Thr 50 55 60Arg Gly Pro Leu Leu Asp Asn Glu Gln Val Asp Met Asp Ile Ala Thr65 70 75 80Phe Thr Ile Thr Asp Glu Arg Lys Lys Leu Tyr Asn Phe Thr Ser Pro 85 90 95Tyr Tyr Thr Asp Ala Ser Gly Phe Leu Val Asn Lys Ser Ala Lys Ile 100 105 110Lys Lys Ile Glu Asp Leu Asn Gly Lys Thr Ile Gly Val Ala Gln Gly 115 120 125Ser Ile Thr Gln Arg Leu Ile Thr Glu Leu Gly Lys Lys Lys Gly Leu 130 135 140Lys Phe Lys Phe Val Glu Leu Gly Ser Tyr Pro Glu Leu Ile Thr Ser145 150 155 160Leu His Ala His Arg Ile Asp Thr Phe Ser Val Asp Arg Ser Ile Leu 165 170 175Ser Gly Tyr Thr Ser Lys Arg Thr Ala Leu Leu Asp Asp Ser Phe Lys 180 185 190Pro Ser Asp Tyr Gly Ile Val Thr Lys Lys Ser Asn Thr Glu Leu Asn 195 200 205Asp Tyr Leu Asp Asn Leu Val Thr Lys Trp Ser Lys Asp Gly Ser Leu 210 215 220Gln Lys Leu Tyr Asp Arg Tyr Lys Leu Lys Pro Ser Ser His Thr Ala225 230 235 240Asp471279DNAStreptococcus pneumoniae 47gtctgtatca tttgaaaaca aagaaacaaa ccgtggtgtc ttgactttca ctatctctca 60agaccaaatc aaaccagaat tggaccgtgt cttcaagtca gtgaagaaat ctcttaatgt 120tccaggtttc cgtaaaggtc accttccacg ccctatcttc gaccaaaaat ttggtgaaga 180agctctttat caagatgcaa tgaacgcact tttgccaaac gcttatgaag cagctgtaaa 240agaagctggt cttgaagtgg ttgcccaacc aaaaattgac gtaacttcaa tggaaaaagg 300tcaagactgg gttatcactg ctgaagtcgt tacaaaacct gaagtaaaat tgggtgacta 360caaaaacctt gaagtatcag ttgatgtaga aaaagaagta actgacgctg atgtcgaaga 420gcgtatcgaa cgcgaacgca acaacctggc tgaattggtt atcaaggaag ctgctgctga 480aaacggcgac actgttgtga tcgacttcgt tggttctatc gacggtgttg aatttgacgg 540tggaaaaggt gaaaacttct cacttggact tggttcaggt caattcatcc ctggtttcga 600agaccaattg gtaggtcact cagctggcga aaccgttgat gttatcgtaa cattcccaga 660agactaccaa gcagaagacc ttgcaggtaa agaagctaaa ttcgtgacaa ctatccacga 720agtaaaagct aaagaagttc cggctcttga cgatgaactt gcaaaagaca ttgatgaaga 780agttgaaaca cttgctgact tgaaagaaaa atacagcaaa gaattggctg ctgctaaaga 840agaagcttac aaagatgcag ttgaaggtgc agcaattgat acagctgtag aaaatgctga 900aatcgtagaa cttccagaag aaatgatcca tgaagaagtt caccgttcag taaatgaatt 960ccttgggaat ttgcaacgtc aagggatcaa ccctgacatg tacttccaaa tcactggaac 1020tactcaagaa gaccttcaca accaatacca agcagaagct gagtcacgta ctaagactaa 1080ccttgttatc gaagcagttg ccaaagctga aggatttgat gcttcagaag aagaaatcca 1140aaaagaagtt gagcaattgg cagcagacta caacatggaa gttgcacaag ttcaaaactt 1200gctttcagct gacatgttga aacatgatat cactatcaaa aaagctgttg aattgatcac 1260aagcacagca acagtaaaa 127948426PRTStreptococcus pneumoniae 48Ser Val Ser Phe Glu Asn Lys Glu Thr Asn Arg Gly Val Leu Thr Phe1 5 10 15Thr Ile Ser Gln Asp Gln Ile Lys Pro Glu Leu Asp Arg Val Phe Lys 20 25 30Ser Val Lys Lys Ser Leu Asn Val Pro Gly Phe Arg Lys Gly His Leu 35 40 45Pro Arg Pro Ile Phe Asp Gln Lys Phe Gly Glu Glu Ala Leu Tyr Gln 50 55 60Asp Ala Met Asn Ala Leu Leu Pro Asn Ala Tyr Glu Ala Ala Val Lys65 70 75 80Glu Ala Gly Leu Glu Val Val Ala Gln Pro Lys Ile Asp Val Thr Ser 85 90 95Met Glu Lys Gly Gln Asp Trp Val Ile Thr Ala Glu Val Val Thr Lys 100 105 110Pro Glu Val Lys Leu Gly Asp Tyr Lys Asn Leu Glu Val Ser Val Asp 115 120 125Val Glu Lys Glu Val Thr Asp Ala Asp Val Glu Glu Arg Ile Glu Arg 130 135 140Glu Arg Asn Asn Leu Ala Glu Leu Val Ile Lys Glu Ala Ala Ala Glu145 150 155 160Asn Gly Asp Thr Val Val Ile Asp Phe Val Gly Ser Ile Asp Gly Val 165 170 175Glu Phe Asp Gly Gly Lys Gly Glu Asn Phe Ser Leu Gly Leu Gly Ser 180 185 190Gly Gln Phe Ile Pro Gly Phe Glu Asp Gln Leu Val Gly His Ser Ala 195 200 205Gly Glu Thr Val Asp Val Ile Val Thr Phe Pro Glu Asp Tyr Gln Ala 210 215 220Glu Asp Leu Ala Gly Lys Glu Ala Lys Phe Val Thr Thr Ile His Glu225 230 235 240Val Lys Ala Lys Glu Val Pro Ala Leu Asp Asp Glu Leu Ala Lys Asp 245 250 255Ile Asp Glu Glu Val Glu Thr Leu Ala Asp Leu Lys Glu Lys Tyr Ser 260 265 270Lys Glu Leu Ala Ala Ala Lys Glu Glu Ala Tyr Lys Asp Ala Val Glu 275 280 285Gly Ala Ala Ile Asp Thr Ala Val Glu Asn Ala Glu Ile Val Glu Leu 290 295 300Pro Glu Glu Met Ile His Glu Glu Val His Arg Ser Val Asn Glu Phe305 310 315 320Leu Gly Asn Leu Gln Arg Gln Gly Ile Asn Pro Asp Met Tyr Phe Gln 325 330 335Ile Thr Gly Thr Thr Gln Glu Asp Leu His Asn Gln Tyr Gln Ala Glu 340

345 350Ala Glu Ser Arg Thr Lys Thr Asn Leu Val Ile Glu Ala Val Ala Lys 355 360 365Ala Glu Gly Phe Asp Ala Ser Glu Glu Glu Ile Gln Lys Glu Val Glu 370 375 380Gln Leu Ala Ala Asp Tyr Asn Met Glu Val Ala Gln Val Gln Asn Leu385 390 395 400Leu Ser Ala Asp Met Leu Lys His Asp Ile Thr Ile Lys Lys Ala Val 405 410 415Glu Leu Ile Thr Ser Thr Ala Thr Val Lys 420 42549490DNAStreptococcus pneumoniae 49tggtcaaaag gaaagtcaga caggaaaggg gatgaaaatt gtgaccagtt tttatcctat 60ctacgctatg gttaaggaag tatctggtga cttgaatgat gttcggatga ttcagtcaag 120tagtggtatt cactcctttg aaccttcggc aaatgatatc gcagccatct atgatgcaga 180tgtctttgtt taccattctc atacactcga atcttgggca ggaagtctgg atccaaatct 240aaaaaaatcc aaagtgaagg tcttagaggc ttctgaggga atgaccttgg aacgtgtccc 300tggactagag gatgtggaag caggggatgg agttgatgaa aaaacgctct atgaccctca 360cacatggcta gatcctgaaa aagctggaga agaagcccaa attatcgctg ataaactttc 420agaggtggat agtgagcata aagagactta tcaaaaaaat gcgcaacctt tatcaaaaaa 480gctcaggaat 49050163PRTStreptococcus pneumoniae 50Gly Gln Lys Glu Ser Gln Thr Gly Lys Gly Met Lys Ile Val Thr Ser1 5 10 15Phe Tyr Pro Ile Tyr Ala Met Val Lys Glu Val Ser Gly Asp Leu Asn 20 25 30Asp Val Arg Met Ile Gln Ser Ser Ser Gly Ile His Ser Phe Glu Pro 35 40 45Ser Ala Asn Asp Ile Ala Ala Ile Tyr Asp Ala Asp Val Phe Val Tyr 50 55 60His Ser His Thr Leu Glu Ser Trp Ala Gly Ser Leu Asp Pro Asn Leu65 70 75 80Lys Lys Ser Lys Val Lys Val Leu Glu Ala Ser Glu Gly Met Thr Leu 85 90 95Glu Arg Val Pro Gly Leu Glu Asp Val Glu Ala Gly Asp Gly Val Asp 100 105 110Glu Lys Thr Leu Tyr Asp Pro His Thr Trp Leu Asp Pro Glu Lys Ala 115 120 125Gly Glu Glu Ala Gln Ile Ile Ala Asp Lys Leu Ser Glu Val Asp Ser 130 135 140Glu His Lys Glu Thr Tyr Gln Lys Asn Ala Gln Pro Leu Ser Lys Lys145 150 155 160Leu Arg Asn511006DNAStreptococcus pneumoniaemisc_feature(935)..(935)n is a, c, g, or t 51gaaggataga tatattttag catttgagac atcctgtgat gagaccagtg tcgccgtctt 60gaaaaacgac gatgagctct tgtccaatgt cattgctagt caaattgaga gtcacaaacg 120ttttggtggc gtagtgcccg aagtagccag tcgtcaccat gtcgaggtca ttacagcctg 180tatcgaggag gcattggcag aagcagggat taccgaagag gacgtgacag ctgttgcggt 240tacctacgga ccaggcttgg tcggagcctt gctagttggt ttgtcagctg ccaaggcctt 300tgcttgggct cacggacttc cactgattcc tgttaatcac atggctgggc acctcatggc 360agctcagagt gtggagcctt tggagtttcc cttgctagcc ctcttggtca gcggcggaca 420cacagagttg gtttatgttt cggaggcagg agattataag attgttgggg aaacccgtga 480tgatgcggtt ggtgaggctt atgataaggt cggccgtgtc atgggcttga cctatcctgc 540aggtcgtgag attgacgagc tggctcatca ggggcaggat atttatgatt tcccccgtgc 600catgattaag gaagataatc tggagttctc cttctcaggt ttgaaatctg cctttatcaa 660tcttcatcac aatgccgagc aaaagggaga aagcctgtct acagaagatt tgtgtgcttc 720cttccaagca gcagttatgg acattctcat ggcaaaaacc aagaaggctt tggagaaata 780tcctgttaaa atcctagttg tggcaggtgg tgtggcagcc aataaaggtc tcagagaacg 840cctagcagcc gaaatcacag atgtcaaggt tatcatcccc cctctgcgac tctgcggaga 900caatgcaggt atgattgcct atgccagcgt cagcnagtgg aacaaagaaa acttcgcagg 960ctgggacctc aatgccaaac caagtcttgc ctttgatacc atggaa 100652335PRTStreptococcus pneumoniaeSITE(312)..(312)Xaa can be any naturally occurring amino acid 52Lys Asp Arg Tyr Ile Leu Ala Phe Glu Thr Ser Cys Asp Glu Thr Ser1 5 10 15Val Ala Val Leu Lys Asn Asp Asp Glu Leu Leu Ser Asn Val Ile Ala 20 25 30Ser Gln Ile Glu Ser His Lys Arg Phe Gly Gly Val Val Pro Glu Val 35 40 45Ala Ser Arg His His Val Glu Val Ile Thr Ala Cys Ile Glu Glu Ala 50 55 60Leu Ala Glu Ala Gly Ile Thr Glu Glu Asp Val Thr Ala Val Ala Val65 70 75 80Thr Tyr Gly Pro Gly Leu Val Gly Ala Leu Leu Val Gly Leu Ser Ala 85 90 95Ala Lys Ala Phe Ala Trp Ala His Gly Leu Pro Leu Ile Pro Val Asn 100 105 110His Met Ala Gly His Leu Met Ala Ala Gln Ser Val Glu Pro Leu Glu 115 120 125Phe Pro Leu Leu Ala Leu Leu Val Ser Gly Gly His Thr Glu Leu Val 130 135 140Tyr Val Ser Glu Ala Gly Asp Tyr Lys Ile Val Gly Glu Thr Arg Asp145 150 155 160Asp Ala Val Gly Glu Ala Tyr Asp Lys Val Gly Arg Val Met Gly Leu 165 170 175Thr Tyr Pro Ala Gly Arg Glu Ile Asp Glu Leu Ala His Gln Gly Gln 180 185 190Asp Ile Tyr Asp Phe Pro Arg Ala Met Ile Lys Glu Asp Asn Leu Glu 195 200 205Phe Ser Phe Ser Gly Leu Lys Ser Ala Phe Ile Asn Leu His His Asn 210 215 220Ala Glu Gln Lys Gly Glu Ser Leu Ser Thr Glu Asp Leu Cys Ala Ser225 230 235 240Phe Gln Ala Ala Val Met Asp Ile Leu Met Ala Lys Thr Lys Lys Ala 245 250 255Leu Glu Lys Tyr Pro Val Lys Ile Leu Val Val Ala Gly Gly Val Ala 260 265 270Ala Asn Lys Gly Leu Arg Glu Arg Leu Ala Ala Glu Ile Thr Asp Val 275 280 285Lys Val Ile Ile Pro Pro Leu Arg Leu Cys Gly Asp Asn Ala Gly Met 290 295 300Ile Ala Tyr Ala Ser Val Ser Xaa Trp Asn Lys Glu Asn Phe Ala Gly305 310 315 320Trp Asp Leu Asn Ala Lys Pro Ser Leu Ala Phe Asp Thr Met Glu 325 330 335531000DNAStreptococcus pneumoniae 53ggtagttaaa gttggtatta acggtttcgg acgtatcggt cgtcttgctt tccgtcgtat 60ccaaaacgta gaaggtgttg aagttacacg catcaacgac cttacagatc cagttatgct 120tgcacacttg ttgaaatacg acacaactca aggtcgtttc gacggtactg ttgaagttaa 180agaaggtgga tttgaagtta acggtaaatt catcaaagtt tctgctgaac gtgatccaga 240acaaatcgac tgggctactg acggtgtaga aatcgttctt gaagctactg gtttctttgc 300taagaaagaa gcagctgaaa aacaccttaa aggtggagct aaaaaagttg ttatcactgc 360tcctggtgga aacgacgtta aaacagttgt attcaacact aaccacgacg ttcttgacgg 420tactgaaaca gttatctcag gtgcttcatg tactacaaac tgcttggctc caatggctaa 480agctcttcaa gacaactttg gtgttgttga aggattgatg actactatcc acgcttacac 540tggtgaccaa atgatccttg acggaccaca ccgtggtggt gaccttcgcc gtgctcgcgc 600tggtgctgca aacatcgttc ctaactcaac tggtgctgca aaagctatcg gtcttgtaat 660cccagaattg aatggtaaac ttgacggatc tgcacaacgc gttccaactc caactggatc 720agttactgaa ttggtagcag ttcttgaaaa gaacgttact gttgatgaag tgaacgcagc 780tatgaaagca gcttcaaacg aatcatacgg ttacacagaa gatccaatcg tatcttcaga 840tatcgtaggt atgtcttacg gttcattgtt tgacgcaact caaactaaag ttcttgacgt 900tgacggtaaa caattggtta aagttgtatc atggtacgac aacgaaatgt catacactgc 960acaacttgtt cgtactcttg gaatacttcg caaaaattgc 100054333PRTStreptococcus pneumoniae 54Val Val Lys Val Gly Ile Asn Gly Phe Gly Arg Ile Gly Arg Leu Ala1 5 10 15Phe Arg Arg Ile Gln Asn Val Glu Gly Val Glu Val Thr Arg Ile Asn 20 25 30Asp Leu Thr Asp Pro Val Met Leu Ala His Leu Leu Lys Tyr Asp Thr 35 40 45Thr Gln Gly Arg Phe Asp Gly Thr Val Glu Val Lys Glu Gly Gly Phe 50 55 60Glu Val Asn Gly Lys Phe Ile Lys Val Ser Ala Glu Arg Asp Pro Glu65 70 75 80Gln Ile Asp Trp Ala Thr Asp Gly Val Glu Ile Val Leu Glu Ala Thr 85 90 95Gly Phe Phe Ala Lys Lys Glu Ala Ala Glu Lys His Leu Lys Gly Gly 100 105 110Ala Lys Lys Val Val Ile Thr Ala Pro Gly Gly Asn Asp Val Lys Thr 115 120 125Val Val Phe Asn Thr Asn His Asp Val Leu Asp Gly Thr Glu Thr Val 130 135 140Ile Ser Gly Ala Ser Cys Thr Thr Asn Cys Leu Ala Pro Met Ala Lys145 150 155 160Ala Leu Gln Asp Asn Phe Gly Val Val Glu Gly Leu Met Thr Thr Ile 165 170 175His Ala Tyr Thr Gly Asp Gln Met Ile Leu Asp Gly Pro His Arg Gly 180 185 190Gly Asp Leu Arg Arg Ala Arg Ala Gly Ala Ala Asn Ile Val Pro Asn 195 200 205Ser Thr Gly Ala Ala Lys Ala Ile Gly Leu Val Ile Pro Glu Leu Asn 210 215 220Gly Lys Leu Asp Gly Ser Ala Gln Arg Val Pro Thr Pro Thr Gly Ser225 230 235 240Val Thr Glu Leu Val Ala Val Leu Glu Lys Asn Val Thr Val Asp Glu 245 250 255Val Asn Ala Ala Met Lys Ala Ala Ser Asn Glu Ser Tyr Gly Tyr Thr 260 265 270Glu Asp Pro Ile Val Ser Ser Asp Ile Val Gly Met Ser Tyr Gly Ser 275 280 285Leu Phe Asp Ala Thr Gln Thr Lys Val Leu Asp Val Asp Gly Lys Gln 290 295 300Leu Val Lys Val Val Ser Trp Tyr Asp Asn Glu Met Ser Tyr Thr Ala305 310 315 320Gln Leu Val Arg Thr Leu Gly Ile Leu Arg Lys Asn Cys 325 330552389DNAStreptococcus pneumoniaemisc_feature(1368)..(1368)n is a, c, g, or t 55ttcttacgag ttgggactgt atcaagctag aacggttaag gaaaataatc gtgtttccta 60tatagatgga aaacaagcga cgcaaaaaac ggagaatttg actcctgatg aggttagcaa 120gcgtgaagga atcaatgctg agcaaatcgt catcaagata acagaccaag gctatgtcac 180ttcacatggc gaccactatc attattacaa tggtaaggtt ccttatgacg ctatcatcag 240tgaagaatta ctcatgaaag atccaaacta taagctaaaa gatgaggata ttgttaatga 300ggtcaagggt ggatatgtta tcaaggtaga tggaaaatac tatgtttacc ttaaggatgc 360tgcccacgcg gataacgtcc gtacaaaaga ggaaatcaat cgacaaaaac aagagcatag 420tcaacatcgt gaaggtggaa ctccaagaaa cgatggtgct gttgccttgg cacgttcgca 480aggacgctat actacagatg atggttatat ctttaatgct tctgatatca tagaggatac 540tggtgatgct tatatcgttc ctcatggaga tcattaccat tacattccta agaatgagtt 600atcagctagc gagttggctg ctgcagaagc cttcctatct ggtcgaggaa atctgtcaaa 660ttcaagaacc tatcgccgac aaaatagcga taacacttca agaacaaact gggtaccttc 720tgtaagcaat ccaggaacta caaatactaa cacaagcaac aacagcaaca ctaacagtca 780agcaagtcaa agtaatgaca ttgatagtct cttgaaacag ctctacaaac tgcctttgag 840tcaacgacat gtagaatctg atggccttgt ctttgatcca gcacaaatca caagtcgaac 900agctagaggt gttgcagtgc cacacggaga tcattaccac ttcatccctt actctcaaat 960gtctgaattg gaagaacgaa tcgctcgtat tattcccctt cgttatcgtt caaaccattg 1020ggtaccagat tcaaggccag aacaaccaag tccacaaccg actccggaac ctagtccagg 1080cccgcaacct gcaccaaatc ttaaaataga ctcaaattct tctttggtta gtcagctggt 1140acgaaaagtt ggggaaggat atgtattcga agaaaagggc atctctcgtt atgtctttgc 1200gaaagattta ccatctgaaa ctgttaaaaa tcttgaaagc aagttatcaa aacaagagag 1260tgtttcacac actttaactg ctaaaaaaga aaatgttgct cctcgtgacc aagaatttta 1320tgataaagca tataatctgt taactgaggc tcataaagcc ttgtttgnaa ataagggtcg 1380taattctgat ttccaagcct tagacaaatt attagaacgc ttgaatgatg aatcgactaa 1440taaagaaaaa ttggtagatg atttattggc attcctagca ccaattaccc atccagagcg 1500acttggcaaa ccaaattctc aaattgagta tactgaagac gaagttcgta ttgctcaatt 1560agctgataag tatacaacgt cagatggtta catttttgat gaacatgata taatcagtga 1620tgaaggagat gcatatgtaa cgcctcatat gggccatagt cactggattg gaaaagatag 1680cctttctgat aaggaaaaag ttgcagctca agcctatact aaagaaaaag gtatcctacc 1740tccatctcca gacgcagatg ttaaagcaaa tccaactgga gatagtgcag cagctattta 1800caatcgtgtg aaaggggaaa aacgaattcc actcgttcga cttccatata tggttgagca 1860tacagttgag gttaaaaacg gtaatttgat tattcctcat aaggatcatt accataatat 1920taaatttgct tggtttgatg atcacacata caaagctcca aatggctata ccttggaaga 1980tttgtttgcg acgattaagt actacgtaga acaccctgac gaacgtccac attctaatga 2040tggatggggc aatgccagtg agcatgtgtt aggcaagaaa gaccacagtg aagatccaaa 2100taagaacttc aaagcggatg aagagccagt agaggaaaca cctgctgagc cagaagtccc 2160tcaagtagag actgaaaaag tagaagccca actcaaagaa gcagaagttt tgcttgcgaa 2220agtaacggat tctagtctga aagccaatgc aacagaaact ctagctggtt tacgaaataa 2280tttgactctt caaattatgg ataacaatag tatcatggca gaagcagaaa aattacttgc 2340gttgttaaaa ggaagtaatc cttcatctgt aagtaaggaa aaaataaac 238956796PRTStreptococcus pneumoniaeSITE(456)..(456)Xaa can be any naturally occurring amino acid 56Ser Tyr Glu Leu Gly Leu Tyr Gln Ala Arg Thr Val Lys Glu Asn Asn1 5 10 15Arg Val Ser Tyr Ile Asp Gly Lys Gln Ala Thr Gln Lys Thr Glu Asn 20 25 30Leu Thr Pro Asp Glu Val Ser Lys Arg Glu Gly Ile Asn Ala Glu Gln 35 40 45Ile Val Ile Lys Ile Thr Asp Gln Gly Tyr Val Thr Ser His Gly Asp 50 55 60His Tyr His Tyr Tyr Asn Gly Lys Val Pro Tyr Asp Ala Ile Ile Ser65 70 75 80Glu Glu Leu Leu Met Lys Asp Pro Asn Tyr Lys Leu Lys Asp Glu Asp 85 90 95Ile Val Asn Glu Val Lys Gly Gly Tyr Val Ile Lys Val Asp Gly Lys 100 105 110Tyr Tyr Val Tyr Leu Lys Asp Ala Ala His Ala Asp Asn Val Arg Thr 115 120 125Lys Glu Glu Ile Asn Arg Gln Lys Gln Glu His Ser Gln His Arg Glu 130 135 140Gly Gly Thr Pro Arg Asn Asp Gly Ala Val Ala Leu Ala Arg Ser Gln145 150 155 160Gly Arg Tyr Thr Thr Asp Asp Gly Tyr Ile Phe Asn Ala Ser Asp Ile 165 170 175Ile Glu Asp Thr Gly Asp Ala Tyr Ile Val Pro His Gly Asp His Tyr 180 185 190His Tyr Ile Pro Lys Asn Glu Leu Ser Ala Ser Glu Leu Ala Ala Ala 195 200 205Glu Ala Phe Leu Ser Gly Arg Gly Asn Leu Ser Asn Ser Arg Thr Tyr 210 215 220Arg Arg Gln Asn Ser Asp Asn Thr Ser Arg Thr Asn Trp Val Pro Ser225 230 235 240Val Ser Asn Pro Gly Thr Thr Asn Thr Asn Thr Ser Asn Asn Ser Asn 245 250 255Thr Asn Ser Gln Ala Ser Gln Ser Asn Asp Ile Asp Ser Leu Leu Lys 260 265 270Gln Leu Tyr Lys Leu Pro Leu Ser Gln Arg His Val Glu Ser Asp Gly 275 280 285Leu Val Phe Asp Pro Ala Gln Ile Thr Ser Arg Thr Ala Arg Gly Val 290 295 300Ala Val Pro His Gly Asp His Tyr His Phe Ile Pro Tyr Ser Gln Met305 310 315 320Ser Glu Leu Glu Glu Arg Ile Ala Arg Ile Ile Pro Leu Arg Tyr Arg 325 330 335Ser Asn His Trp Val Pro Asp Ser Arg Pro Glu Gln Pro Ser Pro Gln 340 345 350Pro Thr Pro Glu Pro Ser Pro Gly Pro Gln Pro Ala Pro Asn Leu Lys 355 360 365Ile Asp Ser Asn Ser Ser Leu Val Ser Gln Leu Val Arg Lys Val Gly 370 375 380Glu Gly Tyr Val Phe Glu Glu Lys Gly Ile Ser Arg Tyr Val Phe Ala385 390 395 400Lys Asp Leu Pro Ser Glu Thr Val Lys Asn Leu Glu Ser Lys Leu Ser 405 410 415Lys Gln Glu Ser Val Ser His Thr Leu Thr Ala Lys Lys Glu Asn Val 420 425 430Ala Pro Arg Asp Gln Glu Phe Tyr Asp Lys Ala Tyr Asn Leu Leu Thr 435 440 445Glu Ala His Lys Ala Leu Phe Xaa Asn Lys Gly Arg Asn Ser Asp Phe 450 455 460Gln Ala Leu Asp Lys Leu Leu Glu Arg Leu Asn Asp Glu Ser Thr Asn465 470 475 480Lys Glu Lys Leu Val Asp Asp Leu Leu Ala Phe Leu Ala Pro Ile Thr 485 490 495His Pro Glu Arg Leu Gly Lys Pro Asn Ser Gln Ile Glu Tyr Thr Glu 500 505 510Asp Glu Val Arg Ile Ala Gln Leu Ala Asp Lys Tyr Thr Thr Ser Asp 515 520 525Gly Tyr Ile Phe Asp Glu His Asp Ile Ile Ser Asp Glu Gly Asp Ala 530 535 540Tyr Val Thr Pro His Met Gly His Ser His Trp Ile Gly Lys Asp Ser545 550 555 560Leu Ser Asp Lys Glu Lys Val Ala Ala Gln Ala Tyr Thr Lys Glu Lys 565 570 575Gly Ile Leu Pro Pro Ser Pro Asp Ala Asp Val Lys Ala Asn Pro Thr 580 585 590Gly Asp Ser Ala Ala Ala Ile Tyr Asn Arg Val Lys Gly Glu Lys Arg 595 600 605Ile Pro Leu Val Arg Leu Pro Tyr Met Val Glu His Thr Val Glu Val 610 615 620Lys Asn Gly Asn Leu Ile Ile Pro His Lys Asp His Tyr His Asn Ile625 630 635 640Lys Phe Ala Trp Phe Asp Asp His Thr Tyr Lys Ala Pro Asn Gly Tyr 645 650 655Thr Leu Glu Asp Leu Phe Ala Thr Ile Lys Tyr Tyr Val Glu His Pro 660 665 670Asp Glu Arg Pro His Ser

Asn Asp Gly Trp Gly Asn Ala Ser Glu His 675 680 685Val Leu Gly Lys Lys Asp His Ser Glu Asp Pro Asn Lys Asn Phe Lys 690 695 700Ala Asp Glu Glu Pro Val Glu Glu Thr Pro Ala Glu Pro Glu Val Pro705 710 715 720Gln Val Glu Thr Glu Lys Val Glu Ala Gln Leu Lys Glu Ala Glu Val 725 730 735Leu Leu Ala Lys Val Thr Asp Ser Ser Leu Lys Ala Asn Ala Thr Glu 740 745 750Thr Leu Ala Gly Leu Arg Asn Asn Leu Thr Leu Gln Ile Met Asp Asn 755 760 765Asn Ser Ile Met Ala Glu Ala Glu Lys Leu Leu Ala Leu Leu Lys Gly 770 775 780Ser Asn Pro Ser Ser Val Ser Lys Glu Lys Ile Asn785 790 795571180DNAStreptococcus pneumoniaemisc_feature(819)..(820)n is a, c, g, or t 57tactgagatg catcataatc taggagctga aaagcgttca gcagtggcta ctactatcga 60tagttttaag gagcgaagtc aaaaagtcag agcactatct gatccaaatg tgcgttttgt 120tcccttcttt ggctctagtg aatggcttcg ttttgacggt gctcattctg cggtattagc 180tgagaaatac aatcgttcct accgtcctta tcttttagga caggggggag ctgcatcgct 240taaccaatat tttggaatgc aacagatgtt accacagctg gagaataaac aagttgtgta 300tgttatctca cctcagtggt tcagtaaaaa tggctatgat ccagcagcct tccagcagta 360ttttaatgga gaccagttga ctagttttct gaaacatcaa tctggggatc aggctagtca 420atatgcagcg actcgcttac tgcaacagtt cccaaacgta gctatgaagg acctggttca 480gaagttggca agtaaagaag aattgtcgac agcagacaat gaaatgattg aattattggc 540tcgttttaat gaacgccaag cttccttttt tggtcagttt tcggttagag gctatgttaa 600ctacgataag catgtagcta agtatttaaa aatcttgcca gaccagtttt cttatcaggc 660aatagaagat gttgtcaaag cagatgctga aaaaaatact tccaataatg agatgggaat 720ggaaaattat ttctataatg agcagatcaa gaaggatttg aagaaattaa aggattctca 780gaaaagcttt acctatctca agtcgccaga gtataatgnn ttgcagttgg ttttaacaca 840gttttctaaa tctaaggtaa acccgatttt tatcattcca cctgttaata aaaaatggat 900gnactatgct ggtctacgag aggatatgta ccaacaaacg gtgcagaaga ttcgctacca 960gttagaaagt caaggtttta ccaatatagc agatttttct aaggacggcg gggagccttt 1020ctttatgaag gacaccattc accttggttg gttgggttgg ttggcttttg acaaggcagt 1080tgatcctttc ctatccaatc ccacaccagc tccgacttac catctgaatg agcgcttttt 1140cagcaaagat tgggcgactt atgatggaga tgtcaaagaa 118058393PRTStreptococcus pneumoniaeSITE(273)..(273)Xaa can be any naturally occurring amino acid 58Thr Glu Met His His Asn Leu Gly Ala Glu Lys Arg Ser Ala Val Ala1 5 10 15Thr Thr Ile Asp Ser Phe Lys Glu Arg Ser Gln Lys Val Arg Ala Leu 20 25 30Ser Asp Pro Asn Val Arg Phe Val Pro Phe Phe Gly Ser Ser Glu Trp 35 40 45Leu Arg Phe Asp Gly Ala His Ser Ala Val Leu Ala Glu Lys Tyr Asn 50 55 60Arg Ser Tyr Arg Pro Tyr Leu Leu Gly Gln Gly Gly Ala Ala Ser Leu65 70 75 80Asn Gln Tyr Phe Gly Met Gln Gln Met Leu Pro Gln Leu Glu Asn Lys 85 90 95Gln Val Val Tyr Val Ile Ser Pro Gln Trp Phe Ser Lys Asn Gly Tyr 100 105 110Asp Pro Ala Ala Phe Gln Gln Tyr Phe Asn Gly Asp Gln Leu Thr Ser 115 120 125Phe Leu Lys His Gln Ser Gly Asp Gln Ala Ser Gln Tyr Ala Ala Thr 130 135 140Arg Leu Leu Gln Gln Phe Pro Asn Val Ala Met Lys Asp Leu Val Gln145 150 155 160Lys Leu Ala Ser Lys Glu Glu Leu Ser Thr Ala Asp Asn Glu Met Ile 165 170 175Glu Leu Leu Ala Arg Phe Asn Glu Arg Gln Ala Ser Phe Phe Gly Gln 180 185 190Phe Ser Val Arg Gly Tyr Val Asn Tyr Asp Lys His Val Ala Lys Tyr 195 200 205Leu Lys Ile Leu Pro Asp Gln Phe Ser Tyr Gln Ala Ile Glu Asp Val 210 215 220Val Lys Ala Asp Ala Glu Lys Asn Thr Ser Asn Asn Glu Met Gly Met225 230 235 240Glu Asn Tyr Phe Tyr Asn Glu Gln Ile Lys Lys Asp Leu Lys Lys Leu 245 250 255Lys Asp Ser Gln Lys Ser Phe Thr Tyr Leu Lys Ser Pro Glu Tyr Asn 260 265 270Xaa Leu Gln Leu Val Leu Thr Gln Phe Ser Lys Ser Lys Val Asn Pro 275 280 285Ile Phe Ile Ile Pro Pro Val Asn Lys Lys Trp Met Xaa Tyr Ala Gly 290 295 300Leu Arg Glu Asp Met Tyr Gln Gln Thr Val Gln Lys Ile Arg Tyr Gln305 310 315 320Leu Glu Ser Gln Gly Phe Thr Asn Ile Ala Asp Phe Ser Lys Asp Gly 325 330 335Gly Glu Pro Phe Phe Met Lys Asp Thr Ile His Leu Gly Trp Leu Gly 340 345 350Trp Leu Ala Phe Asp Lys Ala Val Asp Pro Phe Leu Ser Asn Pro Thr 355 360 365Pro Ala Pro Thr Tyr His Leu Asn Glu Arg Phe Phe Ser Lys Asp Trp 370 375 380Ala Thr Tyr Asp Gly Asp Val Lys Glu385 390591423DNAStreptococcus pneumoniae 59ggttttgaga aagtatttgc agggggccct gattgagtcg attgagcaag tggaaaatga 60ccgtattgtg gaaattacag tttccaataa aaacgagatt ggagaccata tccaggctac 120cttgattatc gaaattatgg ggaaacacag taatattcta ctggtcgata aaagcagtca 180taaaatcctc gaagttatca aacacgtcgg cttttcacaa aatagctacc gcaccttact 240tccaggatcg acctatatcg ctccgccaag tacaaaatct ctcaatcctt ttactatcaa 300ggatgaaaag ctctttgaaa tcctgcaaac ccaagaacta acagcaaaaa atcttcaaag 360cctctttcaa ggtctgggac gcgatacggc aaatgaattg gaaaggatac tggttagtga 420aaaactttcc gctttccgaa attttttcaa tcaagaaacc aagccatgct tgactgagac 480ttccttcagt ccagttcctt ttgcaaatca ggtgggagag ccttttgcaa atctttctga 540tttgttggac acctactata aggataaggc tgagcgcgac cgcgtcaaac agcaggccag 600tgaactgatt cgtcgtgttg aaaatgaact tcagaaaaac cgacacaaac tcaaaaaaca 660ggaaaaagag ttactggcga cagacaacgc tgaagaattt cgtcaaaaag gagaattgct 720gacaaccttc ctccaccaag tgcctaacga ccaagaccag gttatcctag acaactacta 780taccaaccaa cctatcatga ttgcgcttga taaggctctg actcccaacc agaatgccca 840acgctatttt aaacggtatc agaaactcaa agaagctgtc aaatacttga ctgatttgat 900tgaagaaacc aaagccacta ttctctatct ggaaagtgta gaaaccgtcc tcaaccaagc 960tggactggaa gaaatcgctg aaatccgtga agaattgatt caaacaggtt ttatccgcag 1020aagacaacgg gagaaaatcc agaaacgcaa aaaactagaa caatatctag caagcgatgg 1080caaaaccatc atctatgtcg gacgaaacaa tcttcaaaat gaggaattga cctttaaaat 1140ggcccgcaag gaggaacttt ggttccatgc taaggacatt cctggaagcc atgttgtcat 1200ctcaggaaat cttgacccat ctgatgcagt caagacagac gcagcagagt tagctgccta 1260cttctctcaa gggcgcctgt cgaatctggt gcaggtagat atgattgaag tcaaaaaact 1320caataaacca actggtggaa aacccggctt tgtcacttac acaggacaaa agaccctccg 1380cgtcacacca gactccaaaa aaattgcatc catgaaaaaa tcc 142360474PRTStreptococcus pneumoniae 60Val Leu Arg Lys Tyr Leu Gln Gly Ala Leu Ile Glu Ser Ile Glu Gln1 5 10 15Val Glu Asn Asp Arg Ile Val Glu Ile Thr Val Ser Asn Lys Asn Glu 20 25 30Ile Gly Asp His Ile Gln Ala Thr Leu Ile Ile Glu Ile Met Gly Lys 35 40 45His Ser Asn Ile Leu Leu Val Asp Lys Ser Ser His Lys Ile Leu Glu 50 55 60Val Ile Lys His Val Gly Phe Ser Gln Asn Ser Tyr Arg Thr Leu Leu65 70 75 80Pro Gly Ser Thr Tyr Ile Ala Pro Pro Ser Thr Lys Ser Leu Asn Pro 85 90 95Phe Thr Ile Lys Asp Glu Lys Leu Phe Glu Ile Leu Gln Thr Gln Glu 100 105 110Leu Thr Ala Lys Asn Leu Gln Ser Leu Phe Gln Gly Leu Gly Arg Asp 115 120 125Thr Ala Asn Glu Leu Glu Arg Ile Leu Val Ser Glu Lys Leu Ser Ala 130 135 140Phe Arg Asn Phe Phe Asn Gln Glu Thr Lys Pro Cys Leu Thr Glu Thr145 150 155 160Ser Phe Ser Pro Val Pro Phe Ala Asn Gln Val Gly Glu Pro Phe Ala 165 170 175Asn Leu Ser Asp Leu Leu Asp Thr Tyr Tyr Lys Asp Lys Ala Glu Arg 180 185 190Asp Arg Val Lys Gln Gln Ala Ser Glu Leu Ile Arg Arg Val Glu Asn 195 200 205Glu Leu Gln Lys Asn Arg His Lys Leu Lys Lys Gln Glu Lys Glu Leu 210 215 220Leu Ala Thr Asp Asn Ala Glu Glu Phe Arg Gln Lys Gly Glu Leu Leu225 230 235 240Thr Thr Phe Leu His Gln Val Pro Asn Asp Gln Asp Gln Val Ile Leu 245 250 255Asp Asn Tyr Tyr Thr Asn Gln Pro Ile Met Ile Ala Leu Asp Lys Ala 260 265 270Leu Thr Pro Asn Gln Asn Ala Gln Arg Tyr Phe Lys Arg Tyr Gln Lys 275 280 285Leu Lys Glu Ala Val Lys Tyr Leu Thr Asp Leu Ile Glu Glu Thr Lys 290 295 300Ala Thr Ile Leu Tyr Leu Glu Ser Val Glu Thr Val Leu Asn Gln Ala305 310 315 320Gly Leu Glu Glu Ile Ala Glu Ile Arg Glu Glu Leu Ile Gln Thr Gly 325 330 335Phe Ile Arg Arg Arg Gln Arg Glu Lys Ile Gln Lys Arg Lys Lys Leu 340 345 350Glu Gln Tyr Leu Ala Ser Asp Gly Lys Thr Ile Ile Tyr Val Gly Arg 355 360 365Asn Asn Leu Gln Asn Glu Glu Leu Thr Phe Lys Met Ala Arg Lys Glu 370 375 380Glu Leu Trp Phe His Ala Lys Asp Ile Pro Gly Ser His Val Val Ile385 390 395 400Ser Gly Asn Leu Asp Pro Ser Asp Ala Val Lys Thr Asp Ala Ala Glu 405 410 415Leu Ala Ala Tyr Phe Ser Gln Gly Arg Leu Ser Asn Leu Val Gln Val 420 425 430Asp Met Ile Glu Val Lys Lys Leu Asn Lys Pro Thr Gly Gly Lys Pro 435 440 445Gly Phe Val Thr Tyr Thr Gly Gln Lys Thr Leu Arg Val Thr Pro Asp 450 455 460Ser Lys Lys Ile Ala Ser Met Lys Lys Ser465 47061544DNAStreptococcus pneumoniae 61gacaacattt actatccata cagtagagtc agcaccagca gaagtgaaag aaattcttga 60aacagtagaa aaagacaaca atggctatat tcccaaccta atcggtctct tggccaatgc 120cccgactgtt ttagaagcct accaaattgt ctcatctatc caccgtcgca acagcctgac 180acccgttgag cgtgaagtgg tgcaaatcac ggcagccgtg accaatggtt gtgccttctg 240tgtcgcaggt cacacagcct tttccatcaa acaaatccag atgaatgatg acttgattca 300agctcttcgc aatcgtactc caattgaaac agatcctaaa ttggataccc tagctaagtt 360taccttggca gttatcaata ccaagggtcg tgtaggagat gaagccttgt ctgagttttt 420agaagctggc tacactcaac aaaatgcctt ggatgtggtt tttggtgtca gcctagcaat 480cctctgtaac tatgccaaca acttagctaa tacaccaatt aatccagaat tgcaacctta 540tgcc 54462181PRTStreptococcus pneumoniae 62Thr Thr Phe Thr Ile His Thr Val Glu Ser Ala Pro Ala Glu Val Lys1 5 10 15Glu Ile Leu Glu Thr Val Glu Lys Asp Asn Asn Gly Tyr Ile Pro Asn 20 25 30Leu Ile Gly Leu Leu Ala Asn Ala Pro Thr Val Leu Glu Ala Tyr Gln 35 40 45Ile Val Ser Ser Ile His Arg Arg Asn Ser Leu Thr Pro Val Glu Arg 50 55 60Glu Val Val Gln Ile Thr Ala Ala Val Thr Asn Gly Cys Ala Phe Cys65 70 75 80Val Ala Gly His Thr Ala Phe Ser Ile Lys Gln Ile Gln Met Asn Asp 85 90 95Asp Leu Ile Gln Ala Leu Arg Asn Arg Thr Pro Ile Glu Thr Asp Pro 100 105 110Lys Leu Asp Thr Leu Ala Lys Phe Thr Leu Ala Val Ile Asn Thr Lys 115 120 125Gly Arg Val Gly Asp Glu Ala Leu Ser Glu Phe Leu Glu Ala Gly Tyr 130 135 140Thr Gln Gln Asn Ala Leu Asp Val Val Phe Gly Val Ser Leu Ala Ile145 150 155 160Leu Cys Asn Tyr Ala Asn Asn Leu Ala Asn Thr Pro Ile Asn Pro Glu 165 170 175Leu Gln Pro Tyr Ala 18063811DNAStreptococcus pneumoniae 63ggctaaggaa agagtggatg tactagctta taaacagggg ttgtttgaaa cgagagagca 60ggccaagcga ggtgtgatgg ctggcctagt cgtagcagtc cttaatggag aacggtttga 120caagccagga gagaaaattc cagatgacac cgaattaaaa ctcaaggggg agaaactcaa 180gtatgtcagc cgtggtggtt tgaaactgga aaaggccttg caggtctttg atttgtcggt 240ggatggcgcg actacgattg atatcggggc ctctactgga ggttttaccg atgtcatgct 300acagaatagt gccaagttgg tctttgcagt cgatgttggt accaatcagt tggcttggaa 360attacgccaa gacccacgag ttgtcagcat ggagcagttc aatttccgct atgctgaaaa 420gactgatttc gagcaggagc cgagctttgc cagtattgat gtgagtttca tttcccttag 480tctgattttg ccagccttgc accgtgtctt ggctgatcaa ggtcaggtgg tagcacttgt 540caaacctcag tttgaggcag gacgtgagca gattgggaaa aatggaatta ttcgagatgc 600taaggttcat cagaatgtcc ttgaatctgt aacagctatg gcagtagagg taggtttttc 660agtccttggc ttggactttt ctcccatcca aggtggacat ggaaatattg aatttttagc 720gtatttgaaa aaagaaaagt cagcaagcaa tcagattctt gctgagatta aagaagcagt 780agagagggcg catagtcaat ttaaaaatga a 81164270PRTStreptococcus pneumoniae 64Ala Lys Glu Arg Val Asp Val Leu Ala Tyr Lys Gln Gly Leu Phe Glu1 5 10 15Thr Arg Glu Gln Ala Lys Arg Gly Val Met Ala Gly Leu Val Val Ala 20 25 30Val Leu Asn Gly Glu Arg Phe Asp Lys Pro Gly Glu Lys Ile Pro Asp 35 40 45Asp Thr Glu Leu Lys Leu Lys Gly Glu Lys Leu Lys Tyr Val Ser Arg 50 55 60Gly Gly Leu Lys Leu Glu Lys Ala Leu Gln Val Phe Asp Leu Ser Val65 70 75 80Asp Gly Ala Thr Thr Ile Asp Ile Gly Ala Ser Thr Gly Gly Phe Thr 85 90 95Asp Val Met Leu Gln Asn Ser Ala Lys Leu Val Phe Ala Val Asp Val 100 105 110Gly Thr Asn Gln Leu Ala Trp Lys Leu Arg Gln Asp Pro Arg Val Val 115 120 125Ser Met Glu Gln Phe Asn Phe Arg Tyr Ala Glu Lys Thr Asp Phe Glu 130 135 140Gln Glu Pro Ser Phe Ala Ser Ile Asp Val Ser Phe Ile Ser Leu Ser145 150 155 160Leu Ile Leu Pro Ala Leu His Arg Val Leu Ala Asp Gln Gly Gln Val 165 170 175Val Ala Leu Val Lys Pro Gln Phe Glu Ala Gly Arg Glu Gln Ile Gly 180 185 190Lys Asn Gly Ile Ile Arg Asp Ala Lys Val His Gln Asn Val Leu Glu 195 200 205Ser Val Thr Ala Met Ala Val Glu Val Gly Phe Ser Val Leu Gly Leu 210 215 220Asp Phe Ser Pro Ile Gln Gly Gly His Gly Asn Ile Glu Phe Leu Ala225 230 235 240Tyr Leu Lys Lys Glu Lys Ser Ala Ser Asn Gln Ile Leu Ala Glu Ile 245 250 255Lys Glu Ala Val Glu Arg Ala His Ser Gln Phe Lys Asn Glu 260 265 270652290DNAStreptococcus pneumoniaemisc_feature(154)..(154)n is a, c, g, or t 65ttgttcctat gaacttggtc gtcaccaagc tggtcaggtt aagaaagagt ctaatcgagt 60ttcttatata gatggtgatc aggctggtca aaaggcagaa aacttgacac cagatgaagt 120cagtaagagg gaggggatca acgccgaaca aatngtnatc aagattacgg atcaaggtta 180tgtgacctct catggagacc attatcatta ctataatggc aaggttcctt atgatgccat 240catcagtgaa gagctcctca tgaaagatcc gaattatcag ttgaaggatt cagacattgt 300caatgaaatc aagggtggtt atgtcattaa ggtaaacggt aaatactatg tntaccttaa 360ggatgcagct catgcggata atattcggac aaaagaagag attaaacgtc agaagcagga 420acgcagtcat aatcataact caagagcaga taatgctgtt gctgcagcca gagcccaagg 480acgttataca acggatgatg ggtatatctt caatgcatct gatatcattg aggacacggg 540tgatgcttat atcgttcctc acggcgacca ttaccattac attcctaaga atgagttatc 600agctagcgag ttagctgctg cagaagccta ttggaatggg aagcagggat ctcgtccttc 660ttcaagttct agttataatg caaatccagc tcaaccaaga ttgtcagaga accacaatct 720gactgtcact ccaacttatc atcaaaatca aggggaaaac atttcaagcc ttttacgtga 780attgtatgct aaacccttat cagaacgcca tgtggaatct gatggcctta ttttcgaccc 840agcgcaaatc acaagtcgaa ccgccagagg tgtagctgtc cctcatggta accattacca 900ctttatccct tatgaacaaa tgtctgaatt ggaaaaacga attgctcgta ttattcccct 960tcgttatcgt tcaaaccatt gggtaccaga ttcaagacca gaacaaccaa gtccacaatc 1020gactccggaa cctagtccaa gtccgcaacc tgcaccaaat cctcaaccag ctccaagcaa 1080tccaattgat gagaaattgg tcaaagaagc tgttcgaaaa gtaggcgatg gttatgtctt 1140tgaggagaat ggagtttctc gttatatccc agccaaggat ctttcagcag aaacagcagc 1200aggcattgat agcaaactgg ccaagcagga aagtttatct cataagctag gagctaagaa 1260aactgacctc ccatctagtg atcgagaatt ttacaataag gcttatgact tactagcaag 1320aattcaccaa gatttacttg ataataaagg tcgacaagtt gattttgagg ctttggataa 1380cctgttggaa cgactcaagg atgtcncaag tgataaagtc aagttagtgg angatattct 1440tgccttctta gctccgattc gtcatccaga acgtttagga aaaccaaatg cgcaaattac 1500ctacactgat gatgagattc aagtagccaa gttggcaggc aagtacacaa cagaagacgg 1560ttatatcttt gatcctcgtg atataaccag tgatgagggg gatgcctatg taactccaca 1620tatgacccat agccactgga ttaaaaaaga tagtttgtct gaagctgaga gagcggcagc 1680ccaggcttat gctaaagaga aaggtttgac ccctccttcg acagaccatc aggattcagg 1740aaatactgag gcaaaaggag cagaagctat ctacaaccgc gtgaaagcag ctaagaaggt 1800gccacttgat cgtatgcctt acaatcttca atatactgta gaagtcaaaa acggtagttt

1860aatcatacct cattatgacc attaccataa catcaaattt gagtggtttg acgaaggcct 1920ttatgaggca cctaaggggt atactcttga ggatcttttg gcgactgtca agtactatgt 1980cgaacatcca aacgaacgtc cgcattcaga taatggtttt ggtaacgcta gcgaccatgt 2040tcaaagaaac aaaaatggtc aagctgatac caatcaaacg gaaaaaccaa gcgaggagaa 2100acctcagaca gaaaaacctg aggaagaaac ccctcgagaa gagaaaccgc aaagcgagaa 2160accagagtct ccaaaaccaa cagaggaacc agaagaatca ccagaggaat cagaagaacc 2220tcaggtcgag actgaaaagg ttgaagaaaa actgagagag gctgaagatt tacttggaaa 2280aatccaggat 229066763PRTStreptococcus pneumoniaeSITE(51)..(51)Xaa can be any naturally occurring amino acid 66Cys Ser Tyr Glu Leu Gly Arg His Gln Ala Gly Gln Val Lys Lys Glu1 5 10 15Ser Asn Arg Val Ser Tyr Ile Asp Gly Asp Gln Ala Gly Gln Lys Ala 20 25 30Glu Asn Leu Thr Pro Asp Glu Val Ser Lys Arg Glu Gly Ile Asn Ala 35 40 45Glu Gln Xaa Val Ile Lys Ile Thr Asp Gln Gly Tyr Val Thr Ser His 50 55 60Gly Asp His Tyr His Tyr Tyr Asn Gly Lys Val Pro Tyr Asp Ala Ile65 70 75 80Ile Ser Glu Glu Leu Leu Met Lys Asp Pro Asn Tyr Gln Leu Lys Asp 85 90 95Ser Asp Ile Val Asn Glu Ile Lys Gly Gly Tyr Val Ile Lys Val Asn 100 105 110Gly Lys Tyr Tyr Val Tyr Leu Lys Asp Ala Ala His Ala Asp Asn Ile 115 120 125Arg Thr Lys Glu Glu Ile Lys Arg Gln Lys Gln Glu Arg Ser His Asn 130 135 140His Asn Ser Arg Ala Asp Asn Ala Val Ala Ala Ala Arg Ala Gln Gly145 150 155 160Arg Tyr Thr Thr Asp Asp Gly Tyr Ile Phe Asn Ala Ser Asp Ile Ile 165 170 175Glu Asp Thr Gly Asp Ala Tyr Ile Val Pro His Gly Asp His Tyr His 180 185 190Tyr Ile Pro Lys Asn Glu Leu Ser Ala Ser Glu Leu Ala Ala Ala Glu 195 200 205Ala Tyr Trp Asn Gly Lys Gln Gly Ser Arg Pro Ser Ser Ser Ser Ser 210 215 220Tyr Asn Ala Asn Pro Ala Gln Pro Arg Leu Ser Glu Asn His Asn Leu225 230 235 240Thr Val Thr Pro Thr Tyr His Gln Asn Gln Gly Glu Asn Ile Ser Ser 245 250 255Leu Leu Arg Glu Leu Tyr Ala Lys Pro Leu Ser Glu Arg His Val Glu 260 265 270Ser Asp Gly Leu Ile Phe Asp Pro Ala Gln Ile Thr Ser Arg Thr Ala 275 280 285Arg Gly Val Ala Val Pro His Gly Asn His Tyr His Phe Ile Pro Tyr 290 295 300Glu Gln Met Ser Glu Leu Glu Lys Arg Ile Ala Arg Ile Ile Pro Leu305 310 315 320Arg Tyr Arg Ser Asn His Trp Val Pro Asp Ser Arg Pro Glu Gln Pro 325 330 335Ser Pro Gln Ser Thr Pro Glu Pro Ser Pro Ser Pro Gln Pro Ala Pro 340 345 350Asn Pro Gln Pro Ala Pro Ser Asn Pro Ile Asp Glu Lys Leu Val Lys 355 360 365Glu Ala Val Arg Lys Val Gly Asp Gly Tyr Val Phe Glu Glu Asn Gly 370 375 380Val Ser Arg Tyr Ile Pro Ala Lys Asp Leu Ser Ala Glu Thr Ala Ala385 390 395 400Gly Ile Asp Ser Lys Leu Ala Lys Gln Glu Ser Leu Ser His Lys Leu 405 410 415Gly Ala Lys Lys Thr Asp Leu Pro Ser Ser Asp Arg Glu Phe Tyr Asn 420 425 430Lys Ala Tyr Asp Leu Leu Ala Arg Ile His Gln Asp Leu Leu Asp Asn 435 440 445Lys Gly Arg Gln Val Asp Phe Glu Ala Leu Asp Asn Leu Leu Glu Arg 450 455 460Leu Lys Asp Val Xaa Ser Asp Lys Val Lys Leu Val Xaa Asp Ile Leu465 470 475 480Ala Phe Leu Ala Pro Ile Arg His Pro Glu Arg Leu Gly Lys Pro Asn 485 490 495Ala Gln Ile Thr Tyr Thr Asp Asp Glu Ile Gln Val Ala Lys Leu Ala 500 505 510Gly Lys Tyr Thr Thr Glu Asp Gly Tyr Ile Phe Asp Pro Arg Asp Ile 515 520 525Thr Ser Asp Glu Gly Asp Ala Tyr Val Thr Pro His Met Thr His Ser 530 535 540His Trp Ile Lys Lys Asp Ser Leu Ser Glu Ala Glu Arg Ala Ala Ala545 550 555 560Gln Ala Tyr Ala Lys Glu Lys Gly Leu Thr Pro Pro Ser Thr Asp His 565 570 575Gln Asp Ser Gly Asn Thr Glu Ala Lys Gly Ala Glu Ala Ile Tyr Asn 580 585 590Arg Val Lys Ala Ala Lys Lys Val Pro Leu Asp Arg Met Pro Tyr Asn 595 600 605Leu Gln Tyr Thr Val Glu Val Lys Asn Gly Ser Leu Ile Ile Pro His 610 615 620Tyr Asp His Tyr His Asn Ile Lys Phe Glu Trp Phe Asp Glu Gly Leu625 630 635 640Tyr Glu Ala Pro Lys Gly Tyr Thr Leu Glu Asp Leu Leu Ala Thr Val 645 650 655Lys Tyr Tyr Val Glu His Pro Asn Glu Arg Pro His Ser Asp Asn Gly 660 665 670Phe Gly Asn Ala Ser Asp His Val Gln Arg Asn Lys Asn Gly Gln Ala 675 680 685Asp Thr Asn Gln Thr Glu Lys Pro Ser Glu Glu Lys Pro Gln Thr Glu 690 695 700Lys Pro Glu Glu Glu Thr Pro Arg Glu Glu Lys Pro Gln Ser Glu Lys705 710 715 720Pro Glu Ser Pro Lys Pro Thr Glu Glu Pro Glu Glu Ser Pro Glu Glu 725 730 735Ser Glu Glu Pro Gln Val Glu Thr Glu Lys Val Glu Glu Lys Leu Arg 740 745 750Glu Ala Glu Asp Leu Leu Gly Lys Ile Gln Asp 755 76067352DNAStreptococcus pneumoniae 67ttataagggt gaattagaaa aaggatacca atttgatggt tgggaaattt ctggtttcga 60aggtaaaaaa gacgctggct atgttattaa tctatcaaaa gataccttta taaaacctgt 120attcaagaaa atagaggaga aaaaggagga agaaaataaa cctacttttg atgtatcgaa 180aaagaaagat aacccacaag taaaccatag tcaattaaat gaaagtcaca gaaaagagga 240tttacaaaga gaagagcatt cacaaaaatc tgattcaact aaggatgtta cagctacagt 300tcttgataaa aacaatatca gtagtaaatc aactactaac aatcctaata ag 35268117PRTStreptococcus pneumoniae 68Tyr Lys Gly Glu Leu Glu Lys Gly Tyr Gln Phe Asp Gly Trp Glu Ile1 5 10 15Ser Gly Phe Glu Gly Lys Lys Asp Ala Gly Tyr Val Ile Asn Leu Ser 20 25 30Lys Asp Thr Phe Ile Lys Pro Val Phe Lys Lys Ile Glu Glu Lys Lys 35 40 45Glu Glu Glu Asn Lys Pro Thr Phe Asp Val Ser Lys Lys Lys Asp Asn 50 55 60Pro Gln Val Asn His Ser Gln Leu Asn Glu Ser His Arg Lys Glu Asp65 70 75 80Leu Gln Arg Glu Glu His Ser Gln Lys Ser Asp Ser Thr Lys Asp Val 85 90 95Thr Ala Thr Val Leu Asp Lys Asn Asn Ile Ser Ser Lys Ser Thr Thr 100 105 110Asn Asn Pro Asn Lys 115691312DNAStreptococcus pneumoniae 69gaatgttcag gctcaagaaa gttcaggaaa taaaatccac tttatcaatg ttcaagaagg 60tggcagtgat gcgattattc ttgaaagcaa tggacatttt gccatggtgg atacaggaga 120agattatgat ttcccagatg gaagtgattc tcgctatcca tggagagaag gaattgaaac 180gtcttataag catgttctaa cagaccgtgt ctttcgtcgt ttgaaggaat tgggtgtcca 240aaaacttgat tttattttgg tgacccatac ccacagtgat catattggaa atgttgatga 300attactgtct acctatccag ttgaccgagt ctatcttaag aaatatagtg atagtcgtat 360tactaattct gaacgtctat gggataatct gtatggctat gataaggttt tacagactgc 420tgcagaaaaa ggtgtttcag ttattcaaaa tatcacacaa ggggatgctc attttcagtt 480tggggacatg gatattcagc tctataatta tgaaaatgaa actgattcat cgggtgaatt 540aaagaaaatt tgggatgaca attccaattc cttgattagc gtggtgaaag tcaatggcaa 600gaaaatttac cttgggggcg atttagataa tgttcatgga gcagaagaca agtatggtcc 660tctcattgga aaagttgatt tgatgaagtt taatcatcac catgatacca acaaatcaaa 720taccaaggat ttcattaaaa atttgagtcc gagtttgatt gttcaaactt cggatagtct 780accttggaaa aatggtgttg atagtgagta tgttaattgg ctcaaagaac gaggaattga 840gagaatcaac gcagccagca aagactatga tgcaacagtt tttgatattc gaaaagacgg 900ttttgtcaat atttcaacat cctacaagcc gattccaagt tttcaagctg gttggcataa 960gagtgcatat gggaactggt ggtatcaagc gcctgattct acaggagagt atgctgtcgg 1020ttggaatgaa atcgaaggtg aatggtatta ctttaaccaa acgggtatct tgttacagaa 1080tcaatggaaa aaatggaaca atcattggtt ctatttgaca gactctggtg cttctgctaa 1140aaattggaag aaaatcgctg gaatctggta ttattttaac aaagaaaacc agatggaaat 1200tggttggatt caagataaag agcagtggta ttatttggat gttgatggtt ctatgaagac 1260aggatggctt caatatatgg ggcaatggta ttactttgct ccatcagggg aa 131270437PRTStreptococcus pneumoniae 70Asn Val Gln Ala Gln Glu Ser Ser Gly Asn Lys Ile His Phe Ile Asn1 5 10 15Val Gln Glu Gly Gly Ser Asp Ala Ile Ile Leu Glu Ser Asn Gly His 20 25 30Phe Ala Met Val Asp Thr Gly Glu Asp Tyr Asp Phe Pro Asp Gly Ser 35 40 45Asp Ser Arg Tyr Pro Trp Arg Glu Gly Ile Glu Thr Ser Tyr Lys His 50 55 60Val Leu Thr Asp Arg Val Phe Arg Arg Leu Lys Glu Leu Gly Val Gln65 70 75 80Lys Leu Asp Phe Ile Leu Val Thr His Thr His Ser Asp His Ile Gly 85 90 95Asn Val Asp Glu Leu Leu Ser Thr Tyr Pro Val Asp Arg Val Tyr Leu 100 105 110Lys Lys Tyr Ser Asp Ser Arg Ile Thr Asn Ser Glu Arg Leu Trp Asp 115 120 125Asn Leu Tyr Gly Tyr Asp Lys Val Leu Gln Thr Ala Ala Glu Lys Gly 130 135 140Val Ser Val Ile Gln Asn Ile Thr Gln Gly Asp Ala His Phe Gln Phe145 150 155 160Gly Asp Met Asp Ile Gln Leu Tyr Asn Tyr Glu Asn Glu Thr Asp Ser 165 170 175Ser Gly Glu Leu Lys Lys Ile Trp Asp Asp Asn Ser Asn Ser Leu Ile 180 185 190Ser Val Val Lys Val Asn Gly Lys Lys Ile Tyr Leu Gly Gly Asp Leu 195 200 205Asp Asn Val His Gly Ala Glu Asp Lys Tyr Gly Pro Leu Ile Gly Lys 210 215 220Val Asp Leu Met Lys Phe Asn His His His Asp Thr Asn Lys Ser Asn225 230 235 240Thr Lys Asp Phe Ile Lys Asn Leu Ser Pro Ser Leu Ile Val Gln Thr 245 250 255Ser Asp Ser Leu Pro Trp Lys Asn Gly Val Asp Ser Glu Tyr Val Asn 260 265 270Trp Leu Lys Glu Arg Gly Ile Glu Arg Ile Asn Ala Ala Ser Lys Asp 275 280 285Tyr Asp Ala Thr Val Phe Asp Ile Arg Lys Asp Gly Phe Val Asn Ile 290 295 300Ser Thr Ser Tyr Lys Pro Ile Pro Ser Phe Gln Ala Gly Trp His Lys305 310 315 320Ser Ala Tyr Gly Asn Trp Trp Tyr Gln Ala Pro Asp Ser Thr Gly Glu 325 330 335Tyr Ala Val Gly Trp Asn Glu Ile Glu Gly Glu Trp Tyr Tyr Phe Asn 340 345 350Gln Thr Gly Ile Leu Leu Gln Asn Gln Trp Lys Lys Trp Asn Asn His 355 360 365Trp Phe Tyr Leu Thr Asp Ser Gly Ala Ser Ala Lys Asn Trp Lys Lys 370 375 380Ile Ala Gly Ile Trp Tyr Tyr Phe Asn Lys Glu Asn Gln Met Glu Ile385 390 395 400Gly Trp Ile Gln Asp Lys Glu Gln Trp Tyr Tyr Leu Asp Val Asp Gly 405 410 415Ser Met Lys Thr Gly Trp Leu Gln Tyr Met Gly Gln Trp Tyr Tyr Phe 420 425 430Ala Pro Ser Gly Glu 435711855DNAStreptococcus pneumoniae 71cttgggtgta acccatatcc agctccttcc agtcttgtct tactactttg tcaatgaatt 60gaaaaaccat gaacgcttgt ctgactacgc ttcaagcaac agcaactaca actggggata 120tgaccctcaa aactacttct ccttgactgg tatgtactca agcgatccta agaatccaga 180aaaacgaatc gcagaattta aaaacctcat caacgaaatc cacaaacgtg gtatgggagc 240tatcctagat gtcgtttata accacacagc caaagtcgat ctctttgaag atttggaacc 300aaactactac cactttatgg atgccgatgg cacacctcga actagctttg gtggtggacg 360cttggggaca acccaccata tgaccaaacg gctcctaatt gactctatca aatacctagt 420tgatacctac aaagtggatg gcttccgttt cgatatgatg ggagaccatg acgccgcttc 480tatcgaagaa gcttacaagg ctgcacgcgc cctcaatcca aacctcatca tgcttggtga 540aggttggaga acctatgccg gtgatgaaaa catgcctact aaagctgctg accaagattg 600gatgaaacat accgatactg tcgctgtctt ttcagatgac atccgtaaca acctcaaatc 660tggttatcca aacgaaggtc aacctgcctt tatcacaggt ggcaagcgtg atgtcaacac 720catctttaaa aatctcattg ctcaaccaac taactttgaa gctgacagcc ctggagatgt 780catccaatac atcgcagccc atgataactt gaccctcttt gacatcattg cccagtctat 840caaaaaagac ccaagcaagg ctgagaacta tgctgaaatc caccgtcgtt tacgacttgg 900aaatctcatg gtcttgacag ctcaaggaac tccatttatc cactccggtc aggaatatgg 960acgtactaaa caattccgtg acccagccta caagactcca gtagcagagg ataaggttcc 1020aaacaaatct cacttgttgc gtgataagga cggcaaccca tttgactatc cttacttcat 1080ccatgactct tacgattcta gtgatgcagt caacaagttt gactggacta aggctacaga 1140tggtaaagct tatcctgaaa atgtcaagag ccgtgactat atgaaaggtt tgattgccct 1200tcgtcaatct acagatgcct tccgacttaa gagtcttcaa gatatcaaag accgtgtcca 1260cctcatcact gtcccaggcc aaaatggtgt ggaaaaagag gatgtagtga ttggctacca 1320aatcactgct ccaaacggcg atatctacgc agtctttgtc aatgcggatg aaaaagctcg 1380cgaatttaat ttgggaactg cctttgcaca tctaagaaat gcggaagttt tggcagatga 1440aaaccaagca ggaccagtcg gaattgccaa cccgaaagga cttgaatgga ctgaaaaagg 1500cttgaaattg aatgccctta cagctactgt tcttcgagtc tctcaaaatg gaactagcca 1560tgagtcaact gcagaagaga aaccagactc aaccccttcc aagcctgaac atcaaaatga 1620agcttctcac cctgcacatc aagacccagc tccagaagct agacctgatt ctactaaacc 1680agatgccaaa gtagctgatg cggaaaataa acctagccaa gctacagctg attcacaagc 1740tgaacaacca gcacaagaag cacaagcatc atctgtaaaa gaagcggttc gaaacgaatc 1800ggtagaaaac tctagcaagg aaaatatacc tgcaacccca gataaacaag ctgaa 185572618PRTStreptococcus pneumoniae 72Leu Gly Val Thr His Ile Gln Leu Leu Pro Val Leu Ser Tyr Tyr Phe1 5 10 15Val Asn Glu Leu Lys Asn His Glu Arg Leu Ser Asp Tyr Ala Ser Ser 20 25 30Asn Ser Asn Tyr Asn Trp Gly Tyr Asp Pro Gln Asn Tyr Phe Ser Leu 35 40 45Thr Gly Met Tyr Ser Ser Asp Pro Lys Asn Pro Glu Lys Arg Ile Ala 50 55 60Glu Phe Lys Asn Leu Ile Asn Glu Ile His Lys Arg Gly Met Gly Ala65 70 75 80Ile Leu Asp Val Val Tyr Asn His Thr Ala Lys Val Asp Leu Phe Glu 85 90 95Asp Leu Glu Pro Asn Tyr Tyr His Phe Met Asp Ala Asp Gly Thr Pro 100 105 110Arg Thr Ser Phe Gly Gly Gly Arg Leu Gly Thr Thr His His Met Thr 115 120 125Lys Arg Leu Leu Ile Asp Ser Ile Lys Tyr Leu Val Asp Thr Tyr Lys 130 135 140Val Asp Gly Phe Arg Phe Asp Met Met Gly Asp His Asp Ala Ala Ser145 150 155 160Ile Glu Glu Ala Tyr Lys Ala Ala Arg Ala Leu Asn Pro Asn Leu Ile 165 170 175Met Leu Gly Glu Gly Trp Arg Thr Tyr Ala Gly Asp Glu Asn Met Pro 180 185 190Thr Lys Ala Ala Asp Gln Asp Trp Met Lys His Thr Asp Thr Val Ala 195 200 205Val Phe Ser Asp Asp Ile Arg Asn Asn Leu Lys Ser Gly Tyr Pro Asn 210 215 220Glu Gly Gln Pro Ala Phe Ile Thr Gly Gly Lys Arg Asp Val Asn Thr225 230 235 240Ile Phe Lys Asn Leu Ile Ala Gln Pro Thr Asn Phe Glu Ala Asp Ser 245 250 255Pro Gly Asp Val Ile Gln Tyr Ile Ala Ala His Asp Asn Leu Thr Leu 260 265 270Phe Asp Ile Ile Ala Gln Ser Ile Lys Lys Asp Pro Ser Lys Ala Glu 275 280 285Asn Tyr Ala Glu Ile His Arg Arg Leu Arg Leu Gly Asn Leu Met Val 290 295 300Leu Thr Ala Gln Gly Thr Pro Phe Ile His Ser Gly Gln Glu Tyr Gly305 310 315 320Arg Thr Lys Gln Phe Arg Asp Pro Ala Tyr Lys Thr Pro Val Ala Glu 325 330 335Asp Lys Val Pro Asn Lys Ser His Leu Leu Arg Asp Lys Asp Gly Asn 340 345 350Pro Phe Asp Tyr Pro Tyr Phe Ile His Asp Ser Tyr Asp Ser Ser Asp 355 360 365Ala Val Asn Lys Phe Asp Trp Thr Lys Ala Thr Asp Gly Lys Ala Tyr 370 375 380Pro Glu Asn Val Lys Ser Arg Asp Tyr Met Lys Gly Leu Ile Ala Leu385 390 395 400Arg Gln Ser Thr Asp Ala Phe Arg Leu Lys Ser Leu Gln Asp Ile Lys 405 410 415Asp Arg Val His Leu Ile Thr Val Pro Gly Gln Asn Gly Val Glu Lys 420 425 430Glu Asp Val Val Ile Gly Tyr Gln Ile Thr Ala Pro Asn Gly Asp Ile 435 440 445Tyr Ala Val Phe Val Asn Ala

Asp Glu Lys Ala Arg Glu Phe Asn Leu 450 455 460Gly Thr Ala Phe Ala His Leu Arg Asn Ala Glu Val Leu Ala Asp Glu465 470 475 480Asn Gln Ala Gly Pro Val Gly Ile Ala Asn Pro Lys Gly Leu Glu Trp 485 490 495Thr Glu Lys Gly Leu Lys Leu Asn Ala Leu Thr Ala Thr Val Leu Arg 500 505 510Val Ser Gln Asn Gly Thr Ser His Glu Ser Thr Ala Glu Glu Lys Pro 515 520 525Asp Ser Thr Pro Ser Lys Pro Glu His Gln Asn Glu Ala Ser His Pro 530 535 540Ala His Gln Asp Pro Ala Pro Glu Ala Arg Pro Asp Ser Thr Lys Pro545 550 555 560Asp Ala Lys Val Ala Asp Ala Glu Asn Lys Pro Ser Gln Ala Thr Ala 565 570 575Asp Ser Gln Ala Glu Gln Pro Ala Gln Glu Ala Gln Ala Ser Ser Val 580 585 590Lys Glu Ala Val Arg Asn Glu Ser Val Glu Asn Ser Ser Lys Glu Asn 595 600 605Ile Pro Ala Thr Pro Asp Lys Gln Ala Glu 610 615731774DNAStreptococcus pneumoniaemisc_feature(73)..(73)n is a, c, g, or t 73tagtgatggt acttggcaag gaaaacagta tctgaaagaa gatggcagtc aagcagcaaa 60tgagtgggtt ttngatactc attatcaatc ttggttctat ataaaagcag atgctaacta 120tgctgaaaat gaatggctaa agcaaggtga cgactatttt tacctcaaat ctggtggcta 180tatggccaaa tcagaatggg tagaagacaa gggagccttt tattatcttg accaagatgg 240aaagatgaaa agaaatgctt gggtaggaac ttcctatgtt ggtgcaacag gtgccaaagt 300aatagaagac tgggtctatg attctcaata cgatgcttgg ttttatatca aagcagatgg 360acagcacgca gagaaagaat ggctccaaat taaagggaag gactattatt tcaaatccgg 420tggttatcta ctgacaagtc agtggattaa tcaagcttat gtgaatgcta gtggtgccaa 480agtacagcaa ggttggcttt ttgacaaaca ataccaatct tggttttaca tcaaagaaaa 540tggaaactat gctgataaag aatggatttt cgagaatggt cactattatt atctaaaatc 600cggtggctac atggcagcca atgaatggat ttgggataag gaatcttggt tttatctcaa 660atttgatggg aaaatggctg aaaaagaatg ggtctacgat tctcatagtc aagcttggta 720ctacttcaaa tccggtggtt acatgacagc caatgaatgg atttgggata aggaatcttg 780gttttacctc aaatctgatg ggaaaatagc tgaaaaagaa tgggtctacg attctcatag 840tcaagcttgg tactacttca aatctggtgg ctacatggcg aaaaatgaga cagtagatgg 900ttatcagctt ggaagcgatg gtaaatggct tggaggaaaa actacaaatg aaaatgctgc 960ttactatcaa gtagtgcctg ttacagccaa tgtttatgat tcagatggtg aaaagctttc 1020ctatatatcg caaggtagtg tcgtatggct agataaggat agaaaaagtg atgacaagcg 1080cttggctatt actatttctg gtttgtcagg ctatatgaaa acagaagatt tacaagcgct 1140agatgctagt aaggacttta tcccttatta tgagagtgat ggccaccgtt tttatcacta 1200tgtggctcag aatgctagta tcccagtagc ttctcatctt tctgatatgg aagtaggcaa 1260gaaatattat tcggcagatg gcctgcattt tgatggtttt aagcttgaga atcccttcct 1320tttcaaagat ttaacagagg ctacaaacta cagtgctgaa gaattggata aggtatttag 1380tttgctaaac attaacaata gccttttgga gaacaagggc gctactttta aggaagccga 1440agaacattac catatcaatg ctctttatct ccttgcccat agtgccctag aaagtaactg 1500gggaagaagt aaaattgcca aagataagaa taatttcttt ggcattacag cctatgatac 1560gaccccttac ctttctgcta agacatttga tgatgtggat aagggaattt taggtgcaac 1620caagtggatt aaggaaaatt atatcgatag gggaagaact ttccttggaa acaaggcttc 1680tggtatgaat gtggaatatg cttcagaccc ttattggggc gaaaaaattg ctagtgtgat 1740gatgaaaatc aatgagaagc taggtggcaa agat 177474591PRTStreptococcus pneumoniaeSITE(24)..(24)Xaa can be any naturally occurring amino acid 74Ser Asp Gly Thr Trp Gln Gly Lys Gln Tyr Leu Lys Glu Asp Gly Ser1 5 10 15Gln Ala Ala Asn Glu Trp Val Xaa Asp Thr His Tyr Gln Ser Trp Phe 20 25 30Tyr Ile Lys Ala Asp Ala Asn Tyr Ala Glu Asn Glu Trp Leu Lys Gln 35 40 45Gly Asp Asp Tyr Phe Tyr Leu Lys Ser Gly Gly Tyr Met Ala Lys Ser 50 55 60Glu Trp Val Glu Asp Lys Gly Ala Phe Tyr Tyr Leu Asp Gln Asp Gly65 70 75 80Lys Met Lys Arg Asn Ala Trp Val Gly Thr Ser Tyr Val Gly Ala Thr 85 90 95Gly Ala Lys Val Ile Glu Asp Trp Val Tyr Asp Ser Gln Tyr Asp Ala 100 105 110Trp Phe Tyr Ile Lys Ala Asp Gly Gln His Ala Glu Lys Glu Trp Leu 115 120 125Gln Ile Lys Gly Lys Asp Tyr Tyr Phe Lys Ser Gly Gly Tyr Leu Leu 130 135 140Thr Ser Gln Trp Ile Asn Gln Ala Tyr Val Asn Ala Ser Gly Ala Lys145 150 155 160Val Gln Gln Gly Trp Leu Phe Asp Lys Gln Tyr Gln Ser Trp Phe Tyr 165 170 175Ile Lys Glu Asn Gly Asn Tyr Ala Asp Lys Glu Trp Ile Phe Glu Asn 180 185 190Gly His Tyr Tyr Tyr Leu Lys Ser Gly Gly Tyr Met Ala Ala Asn Glu 195 200 205Trp Ile Trp Asp Lys Glu Ser Trp Phe Tyr Leu Lys Phe Asp Gly Lys 210 215 220Met Ala Glu Lys Glu Trp Val Tyr Asp Ser His Ser Gln Ala Trp Tyr225 230 235 240Tyr Phe Lys Ser Gly Gly Tyr Met Thr Ala Asn Glu Trp Ile Trp Asp 245 250 255Lys Glu Ser Trp Phe Tyr Leu Lys Ser Asp Gly Lys Ile Ala Glu Lys 260 265 270Glu Trp Val Tyr Asp Ser His Ser Gln Ala Trp Tyr Tyr Phe Lys Ser 275 280 285Gly Gly Tyr Met Ala Lys Asn Glu Thr Val Asp Gly Tyr Gln Leu Gly 290 295 300Ser Asp Gly Lys Trp Leu Gly Gly Lys Thr Thr Asn Glu Asn Ala Ala305 310 315 320Tyr Tyr Gln Val Val Pro Val Thr Ala Asn Val Tyr Asp Ser Asp Gly 325 330 335Glu Lys Leu Ser Tyr Ile Ser Gln Gly Ser Val Val Trp Leu Asp Lys 340 345 350Asp Arg Lys Ser Asp Asp Lys Arg Leu Ala Ile Thr Ile Ser Gly Leu 355 360 365Ser Gly Tyr Met Lys Thr Glu Asp Leu Gln Ala Leu Asp Ala Ser Lys 370 375 380Asp Phe Ile Pro Tyr Tyr Glu Ser Asp Gly His Arg Phe Tyr His Tyr385 390 395 400Val Ala Gln Asn Ala Ser Ile Pro Val Ala Ser His Leu Ser Asp Met 405 410 415Glu Val Gly Lys Lys Tyr Tyr Ser Ala Asp Gly Leu His Phe Asp Gly 420 425 430Phe Lys Leu Glu Asn Pro Phe Leu Phe Lys Asp Leu Thr Glu Ala Thr 435 440 445Asn Tyr Ser Ala Glu Glu Leu Asp Lys Val Phe Ser Leu Leu Asn Ile 450 455 460Asn Asn Ser Leu Leu Glu Asn Lys Gly Ala Thr Phe Lys Glu Ala Glu465 470 475 480Glu His Tyr His Ile Asn Ala Leu Tyr Leu Leu Ala His Ser Ala Leu 485 490 495Glu Ser Asn Trp Gly Arg Ser Lys Ile Ala Lys Asp Lys Asn Asn Phe 500 505 510Phe Gly Ile Thr Ala Tyr Asp Thr Thr Pro Tyr Leu Ser Ala Lys Thr 515 520 525Phe Asp Asp Val Asp Lys Gly Ile Leu Gly Ala Thr Lys Trp Ile Lys 530 535 540Glu Asn Tyr Ile Asp Arg Gly Arg Thr Phe Leu Gly Asn Lys Ala Ser545 550 555 560Gly Met Asn Val Glu Tyr Ala Ser Asp Pro Tyr Trp Gly Glu Lys Ile 565 570 575Ala Ser Val Met Met Lys Ile Asn Glu Lys Leu Gly Gly Lys Asp 580 585 590751105DNAStreptococcus pneumoniae 75tgggattcaa tatgtcagag atgatactag agataaagaa gagggaatag agtatgatga 60cgctgacaat ggggatatta ttgtaaaagt agcgactaaa cctaaggtag taaccaagaa 120aatttcaagt acgcgaattc gttatgaaaa agatgaaaca aaagaccgta gtgaaaatcc 180tgttacaatt gatggagagg atggctatgt aactacgaca aggacctacg atgttaatcc 240agagactggt tatgttaccg aacaggttac tgttgataga aaagaagcca cggatacagt 300tatcaaagtt ccagctaaaa gcaaggttga agaagttctt gttccatttg ctactaaata 360tgaagcagac aatgaccttt ctgcaggaca ggagcaagag attactctag gaaagaatgg 420gaaaacagtt acaacgataa cttataatgt agatggaaag agtggacaag taactgagag 480tactttaagt caaaaaaaag actctcaaac aagagttgtt aaaaaaagaa ccarkcccca 540agttcttgtc caagaaattc caatcgaaac agaatatctc gatggcccaa ctcttgataa 600aagtcaagaa gtagaagaag taggagaaat tggtaaatta ctcttactac aatctatact 660ggtagatgaa cgtgatggaa caattgaaga aactacttct cgtcaaatta ctaaagagat 720ggtaaaaaga cgtataagga gagggacgag agaacctgaa aaagttgttg ttcctgagca 780atcatctatt ccttcgtatc ctgtatctgt tacatctaac caaggaacag atgtagcagt 840agaaccagct aaagcagttg ctccaacaac agactggaaa caagaaaatg gtatgtggta 900tttttataat actgatggtt ccatggcaac aggttgggta caagttaata gttcatggta 960ctacctcaac agcaacggtt ctatgaaagt caatcaatgg ttccaagttg gtggtaaatg 1020gtattatgta aatacatcgg gtgagttagc ggtcaataca agtatagatg gctatagagt 1080caatgataat ggtgaatggg tgcgt 110576368PRTStreptococcus pneumoniaeSITE(178)..(178)Xaa can be any naturally occurring amino acid 76Gly Ile Gln Tyr Val Arg Asp Asp Thr Arg Asp Lys Glu Glu Gly Ile1 5 10 15Glu Tyr Asp Asp Ala Asp Asn Gly Asp Ile Ile Val Lys Val Ala Thr 20 25 30Lys Pro Lys Val Val Thr Lys Lys Ile Ser Ser Thr Arg Ile Arg Tyr 35 40 45Glu Lys Asp Glu Thr Lys Asp Arg Ser Glu Asn Pro Val Thr Ile Asp 50 55 60Gly Glu Asp Gly Tyr Val Thr Thr Thr Arg Thr Tyr Asp Val Asn Pro65 70 75 80Glu Thr Gly Tyr Val Thr Glu Gln Val Thr Val Asp Arg Lys Glu Ala 85 90 95Thr Asp Thr Val Ile Lys Val Pro Ala Lys Ser Lys Val Glu Glu Val 100 105 110Leu Val Pro Phe Ala Thr Lys Tyr Glu Ala Asp Asn Asp Leu Ser Ala 115 120 125Gly Gln Glu Gln Glu Ile Thr Leu Gly Lys Asn Gly Lys Thr Val Thr 130 135 140Thr Ile Thr Tyr Asn Val Asp Gly Lys Ser Gly Gln Val Thr Glu Ser145 150 155 160Thr Leu Ser Gln Lys Lys Asp Ser Gln Thr Arg Val Val Lys Lys Arg 165 170 175Thr Xaa Pro Gln Val Leu Val Gln Glu Ile Pro Ile Glu Thr Glu Tyr 180 185 190Leu Asp Gly Pro Thr Leu Asp Lys Ser Gln Glu Val Glu Glu Val Gly 195 200 205Glu Ile Gly Lys Leu Leu Leu Leu Gln Ser Ile Leu Val Asp Glu Arg 210 215 220Asp Gly Thr Ile Glu Glu Thr Thr Ser Arg Gln Ile Thr Lys Glu Met225 230 235 240Val Lys Arg Arg Ile Arg Arg Gly Thr Arg Glu Pro Glu Lys Val Val 245 250 255Val Pro Glu Gln Ser Ser Ile Pro Ser Tyr Pro Val Ser Val Thr Ser 260 265 270Asn Gln Gly Thr Asp Val Ala Val Glu Pro Ala Lys Ala Val Ala Pro 275 280 285Thr Thr Asp Trp Lys Gln Glu Asn Gly Met Trp Tyr Phe Tyr Asn Thr 290 295 300Asp Gly Ser Met Ala Thr Gly Trp Val Gln Val Asn Ser Ser Trp Tyr305 310 315 320Tyr Leu Asn Ser Asn Gly Ser Met Lys Val Asn Gln Trp Phe Gln Val 325 330 335Gly Gly Lys Trp Tyr Tyr Val Asn Thr Ser Gly Glu Leu Ala Val Asn 340 345 350Thr Ser Ile Asp Gly Tyr Arg Val Asn Asp Asn Gly Glu Trp Val Arg 355 360 36577661DNAStreptococcus pneumoniae 77ggataataga gaagcattaa aaacctttat gacgggtgaa aatttttatc tccaacatta 60tctaggagca catagggaag aactaaatgg agagcatggc tataccttcc gtgtttgggc 120acctaatgct caggctgttc acttggttgg tgattttacc aactggattg aaaatcagat 180tccaatggta agaaatgatt ttggggtctg ggaagtcttt accaatatgg ctcaagaagg 240gcatatttac aaatatcatg tcacacgtca aaatggtcat caactgatga agattgaccc 300ttttgctgtc aggtatgagg ctcgtccagg aacaggggca atcgtaacag agcttcctga 360gaagaaatgg aaggatggac tttggctggc acgaagaaaa cgttggggct ttgaagagcg 420tcctgtcaat atttatgaag ttcacgctgg atcatggaaa agaaattctg atggcagtcc 480ttatagtttt gcccagctca aggatgaact cattccttat ctcgttgaaa tgaactatac 540tcatattgag tttatgccct tgatgtccca tcctttgggc ttgagttggg ggtatcagct 600tatgggttac ttcgctttag agcatgctta tggccgacca gaggagtttc aagattttgt 660c 66178220PRTStreptococcus pneumoniae 78Asp Asn Arg Glu Ala Leu Lys Thr Phe Met Thr Gly Glu Asn Phe Tyr1 5 10 15Leu Gln His Tyr Leu Gly Ala His Arg Glu Glu Leu Asn Gly Glu His 20 25 30Gly Tyr Thr Phe Arg Val Trp Ala Pro Asn Ala Gln Ala Val His Leu 35 40 45Val Gly Asp Phe Thr Asn Trp Ile Glu Asn Gln Ile Pro Met Val Arg 50 55 60Asn Asp Phe Gly Val Trp Glu Val Phe Thr Asn Met Ala Gln Glu Gly65 70 75 80His Ile Tyr Lys Tyr His Val Thr Arg Gln Asn Gly His Gln Leu Met 85 90 95Lys Ile Asp Pro Phe Ala Val Arg Tyr Glu Ala Arg Pro Gly Thr Gly 100 105 110Ala Ile Val Thr Glu Leu Pro Glu Lys Lys Trp Lys Asp Gly Leu Trp 115 120 125Leu Ala Arg Arg Lys Arg Trp Gly Phe Glu Glu Arg Pro Val Asn Ile 130 135 140Tyr Glu Val His Ala Gly Ser Trp Lys Arg Asn Ser Asp Gly Ser Pro145 150 155 160Tyr Ser Phe Ala Gln Leu Lys Asp Glu Leu Ile Pro Tyr Leu Val Glu 165 170 175Met Asn Tyr Thr His Ile Glu Phe Met Pro Leu Met Ser His Pro Leu 180 185 190Gly Leu Ser Trp Gly Tyr Gln Leu Met Gly Tyr Phe Ala Leu Glu His 195 200 205Ala Tyr Gly Arg Pro Glu Glu Phe Gln Asp Phe Val 210 215 22079976DNAStreptococcus pneumoniaemisc_feature(60)..(60)n is a, c, g, or t 79agattttgtc gaggagtgtc atacccataa tattggggtt attgtggact gggtaccagn 60tcactttacc atcaacgatg atgccttagc ctattatgat gggacaccga cttttgaata 120ccaagaccat aataaggctc ataaccatgg ttggggtgcc cttaattttg accttggaaa 180aaatgaagtc cagtccttct taatttcttg cattaagcat tggattgatg tctatcattt 240ggatggtatt cgtgtggatg ctgttagcaa catgctctat ttggactatg atgatgctcc 300atggacacct aataaagatg gcggaaatct caactatgaa ggttattatt tccttcagcg 360cttgaatgag gttattaagt tagaatatcc agatgtgatg atgattgcag aagaaagttc 420gtctgcgatc aagattacgg gaatgaaaga gattggtggt ctaggatttg actacaaatg 480gaacatgggc tggatgaatg atatcctccg tttctacgaa gaagatccga tctatcgtaa 540atatgacttt aacctggtga ctttcagctt tatgtatgtt tncaaggaga attatctctt 600gccattctcg cacgatgaag tggttcatgg caagaagagt atgatgcata agatgtgggg 660agatcgttac aatcaattcg caggcttgcg caatctctat acgtaccaaa tttgtcaccc 720tggtaagaaa ttgctcttca tgggtagcga atacggtcaa ttcctagaat ggaaatctga 780agaacagttg gaatggtcta acctagaaga cccaatgaat gctaagatga agtatttcgc 840ttctcagcta aaccagtttt acaaagatca tcgctgtctg tgggaaattg ataccagcta 900tgatggtatt gaaatcattg atgcggataa tcgagaccag agtgttcttt cctttattcg 960taagggtaaa aaggga 97680325PRTStreptococcus pneumoniaeSITE(20)..(20)Xaa can be any naturally occurring amino acid 80Asp Phe Val Glu Glu Cys His Thr His Asn Ile Gly Val Ile Val Asp1 5 10 15Trp Val Pro Xaa His Phe Thr Ile Asn Asp Asp Ala Leu Ala Tyr Tyr 20 25 30Asp Gly Thr Pro Thr Phe Glu Tyr Gln Asp His Asn Lys Ala His Asn 35 40 45His Gly Trp Gly Ala Leu Asn Phe Asp Leu Gly Lys Asn Glu Val Gln 50 55 60Ser Phe Leu Ile Ser Cys Ile Lys His Trp Ile Asp Val Tyr His Leu65 70 75 80Asp Gly Ile Arg Val Asp Ala Val Ser Asn Met Leu Tyr Leu Asp Tyr 85 90 95Asp Asp Ala Pro Trp Thr Pro Asn Lys Asp Gly Gly Asn Leu Asn Tyr 100 105 110Glu Gly Tyr Tyr Phe Leu Gln Arg Leu Asn Glu Val Ile Lys Leu Glu 115 120 125Tyr Pro Asp Val Met Met Ile Ala Glu Glu Ser Ser Ser Ala Ile Lys 130 135 140Ile Thr Gly Met Lys Glu Ile Gly Gly Leu Gly Phe Asp Tyr Lys Trp145 150 155 160Asn Met Gly Trp Met Asn Asp Ile Leu Arg Phe Tyr Glu Glu Asp Pro 165 170 175Ile Tyr Arg Lys Tyr Asp Phe Asn Leu Val Thr Phe Ser Phe Met Tyr 180 185 190Val Xaa Lys Glu Asn Tyr Leu Leu Pro Phe Ser His Asp Glu Val Val 195 200 205His Gly Lys Lys Ser Met Met His Lys Met Trp Gly Asp Arg Tyr Asn 210 215 220Gln Phe Ala Gly Leu Arg Asn Leu Tyr Thr Tyr Gln Ile Cys His Pro225 230 235 240Gly Lys Lys Leu Leu Phe Met Gly Ser Glu Tyr Gly Gln Phe Leu Glu 245 250 255Trp Lys Ser Glu Glu Gln Leu Glu Trp Ser Asn Leu Glu Asp Pro Met 260 265 270Asn Ala Lys Met Lys Tyr Phe Ala Ser Gln Leu Asn Gln Phe Tyr Lys

275 280 285Asp His Arg Cys Leu Trp Glu Ile Asp Thr Ser Tyr Asp Gly Ile Glu 290 295 300Ile Ile Asp Ala Asp Asn Arg Asp Gln Ser Val Leu Ser Phe Ile Arg305 310 315 320Lys Gly Lys Lys Gly 325812134DNAStreptococcus pneumoniaemisc_feature(167)..(167)n is a, c, g, or t 81atctgtagtt tatgcggatg aaacacttat tactcatact gctgagaaac ctaaagagga 60aaaaatgata gtagaagaaa aggctgataa agctttggaa actaaaaata tagttgaaag 120gacagaacaa agtgaaccta gttcaactga ggctattgca tctgagnaga aagaagatga 180agccgtaact ccaaaagagg aaaaagtgtc tgctaaaccg gaagaaaaag ctccaaggat 240agaatcacaa gcttcaaatc aagaaaaacc gctcaaggaa gatgctaaag ctgtaacaaa 300tgaagaagtg aatcaaatga ttgaagacag gaaagtggat tttaatcaaa attggtactt 360taaactcaat gcaaattcta aggaagccat taaacctgat gcagacgtat ctacgtggaa 420aaaattagat ttaccgtatg actggagtat ctttaacgat ttcgatcatg aatctcctgc 480acaaaatgaa ggtggacagc tcaacggtgg ggaagcttgg tatcgcaaga ctttcaaact 540agatgaaaaa gacctcaaga aaaatgttcg ccttactttt gatggcgtct acatggattc 600tcaagtttat gtcaatggtc agttagtggg gcattatcca aatggttata accagttctc 660atatgatatc accaaatacc ttcaaaaaga tggtcgtgag aatgtgattg ctgtccatgc 720agtcaacaaa cagccaagta gccgttggta ttcaggaagt ggtatctatc gtgatgtgac 780tttacaagtg acagataagg tgcatgttga gaaaaatggg acaactattt taacaccaaa 840acttgaagaa caacaacatg gcaaggttga aactcatgtg accagcaaaa tcgtcaatac 900ggacgacaaa gaccatgaac ttgtagccga atatcaaatc gttgaacgag gtggtcatgc 960tgtaacaggc ttagttcgta cagcgagtcg taccttaaaa gcacatgaat caacaagcct 1020agatgcgatt ttagaagttg aaagaccaaa actctggact gttttaaatg acaaacctgc 1080cttgtacgaa ttgattacgc gtgtttaccg tgacggtcaa ttggttgatg ctaagaagga 1140tttgtttggt taccgttact atcactggac tccaaatgaa ggtttctctt tgaatggtga 1200acgtattaaa ttccatggag tatccttgca ccacgaccat ggggcgcttg gagcagaaga 1260aaactataaa gcagaatatc gccgtctcaa acaaatgaag gagatgggag ttaactccat 1320ccgtacaacc cacaaccctg ctagtgagca aaccttgcaa atcgcagcag aactaggttt 1380actcgttcag gaagaggcct ttgatacgtg gtatggtggc aagaaacctt atgactatgg 1440acgtttcttt gaaaaagatg ccactcaccc agaagctcga aaaggtgaaa aatggtctga 1500ttttgaccta cgtaccatgg tcgaaagagg caaaaacaac cctgctatct tcatgtggtc 1560aattggtaat gaaataggtg aagctaatgg tgatgcccac tctttagcaa ctgttaaacg 1620tttggttaag gttatcaagg atgttgataa gactcgctat gttaccatgg gagcagataa 1680attccgtttc ggtaatggta gcggagggca tgagaaaatt gctgatgaac tcgatgctgt 1740tggatttaac tattctgaag ataattacaa agcccttaga gctaagcatc caaaatggtt 1800gatttatgga tcagaaacat cttcagctac ccgtacacgt ggaagttact atcgccctga 1860acgtgaattg aaacatagca atggacctga gcgtaattat gaacagtcag attatggaaa 1920tgatcgtgtg ggttggggga aaacagcaac cgcttcatgg acttttgacc gtgacaacgc 1980tggctatgct ggacagttta tctggacagg tacggactat attggtgaac ctacaccatg 2040gcacaaccaa aatcaaactc ctgttaagag ctcttacttt ggtatcgtag atacagccgg 2100cattccaaaa catgacttct atctctacca aagc 213482711PRTStreptococcus pneumoniaeSITE(56)..(56)Xaa can be any naturally occurring amino acid 82Ser Val Val Tyr Ala Asp Glu Thr Leu Ile Thr His Thr Ala Glu Lys1 5 10 15Pro Lys Glu Glu Lys Met Ile Val Glu Glu Lys Ala Asp Lys Ala Leu 20 25 30Glu Thr Lys Asn Ile Val Glu Arg Thr Glu Gln Ser Glu Pro Ser Ser 35 40 45Thr Glu Ala Ile Ala Ser Glu Xaa Lys Glu Asp Glu Ala Val Thr Pro 50 55 60Lys Glu Glu Lys Val Ser Ala Lys Pro Glu Glu Lys Ala Pro Arg Ile65 70 75 80Glu Ser Gln Ala Ser Asn Gln Glu Lys Pro Leu Lys Glu Asp Ala Lys 85 90 95Ala Val Thr Asn Glu Glu Val Asn Gln Met Ile Glu Asp Arg Lys Val 100 105 110Asp Phe Asn Gln Asn Trp Tyr Phe Lys Leu Asn Ala Asn Ser Lys Glu 115 120 125Ala Ile Lys Pro Asp Ala Asp Val Ser Thr Trp Lys Lys Leu Asp Leu 130 135 140Pro Tyr Asp Trp Ser Ile Phe Asn Asp Phe Asp His Glu Ser Pro Ala145 150 155 160Gln Asn Glu Gly Gly Gln Leu Asn Gly Gly Glu Ala Trp Tyr Arg Lys 165 170 175Thr Phe Lys Leu Asp Glu Lys Asp Leu Lys Lys Asn Val Arg Leu Thr 180 185 190Phe Asp Gly Val Tyr Met Asp Ser Gln Val Tyr Val Asn Gly Gln Leu 195 200 205Val Gly His Tyr Pro Asn Gly Tyr Asn Gln Phe Ser Tyr Asp Ile Thr 210 215 220Lys Tyr Leu Gln Lys Asp Gly Arg Glu Asn Val Ile Ala Val His Ala225 230 235 240Val Asn Lys Gln Pro Ser Ser Arg Trp Tyr Ser Gly Ser Gly Ile Tyr 245 250 255Arg Asp Val Thr Leu Gln Val Thr Asp Lys Val His Val Glu Lys Asn 260 265 270Gly Thr Thr Ile Leu Thr Pro Lys Leu Glu Glu Gln Gln His Gly Lys 275 280 285Val Glu Thr His Val Thr Ser Lys Ile Val Asn Thr Asp Asp Lys Asp 290 295 300His Glu Leu Val Ala Glu Tyr Gln Ile Val Glu Arg Gly Gly His Ala305 310 315 320Val Thr Gly Leu Val Arg Thr Ala Ser Arg Thr Leu Lys Ala His Glu 325 330 335Ser Thr Ser Leu Asp Ala Ile Leu Glu Val Glu Arg Pro Lys Leu Trp 340 345 350Thr Val Leu Asn Asp Lys Pro Ala Leu Tyr Glu Leu Ile Thr Arg Val 355 360 365Tyr Arg Asp Gly Gln Leu Val Asp Ala Lys Lys Asp Leu Phe Gly Tyr 370 375 380Arg Tyr Tyr His Trp Thr Pro Asn Glu Gly Phe Ser Leu Asn Gly Glu385 390 395 400Arg Ile Lys Phe His Gly Val Ser Leu His His Asp His Gly Ala Leu 405 410 415Gly Ala Glu Glu Asn Tyr Lys Ala Glu Tyr Arg Arg Leu Lys Gln Met 420 425 430Lys Glu Met Gly Val Asn Ser Ile Arg Thr Thr His Asn Pro Ala Ser 435 440 445Glu Gln Thr Leu Gln Ile Ala Ala Glu Leu Gly Leu Leu Val Gln Glu 450 455 460Glu Ala Phe Asp Thr Trp Tyr Gly Gly Lys Lys Pro Tyr Asp Tyr Gly465 470 475 480Arg Phe Phe Glu Lys Asp Ala Thr His Pro Glu Ala Arg Lys Gly Glu 485 490 495Lys Trp Ser Asp Phe Asp Leu Arg Thr Met Val Glu Arg Gly Lys Asn 500 505 510Asn Pro Ala Ile Phe Met Trp Ser Ile Gly Asn Glu Ile Gly Glu Ala 515 520 525Asn Gly Asp Ala His Ser Leu Ala Thr Val Lys Arg Leu Val Lys Val 530 535 540Ile Lys Asp Val Asp Lys Thr Arg Tyr Val Thr Met Gly Ala Asp Lys545 550 555 560Phe Arg Phe Gly Asn Gly Ser Gly Gly His Glu Lys Ile Ala Asp Glu 565 570 575Leu Asp Ala Val Gly Phe Asn Tyr Ser Glu Asp Asn Tyr Lys Ala Leu 580 585 590Arg Ala Lys His Pro Lys Trp Leu Ile Tyr Gly Ser Glu Thr Ser Ser 595 600 605Ala Thr Arg Thr Arg Gly Ser Tyr Tyr Arg Pro Glu Arg Glu Leu Lys 610 615 620His Ser Asn Gly Pro Glu Arg Asn Tyr Glu Gln Ser Asp Tyr Gly Asn625 630 635 640Asp Arg Val Gly Trp Gly Lys Thr Ala Thr Ala Ser Trp Thr Phe Asp 645 650 655Arg Asp Asn Ala Gly Tyr Ala Gly Gln Phe Ile Trp Thr Gly Thr Asp 660 665 670Tyr Ile Gly Glu Pro Thr Pro Trp His Asn Gln Asn Gln Thr Pro Val 675 680 685Lys Ser Ser Tyr Phe Gly Ile Val Asp Thr Ala Gly Ile Pro Lys His 690 695 700Asp Phe Tyr Leu Tyr Gln Ser705 710832167DNAStreptococcus pneumoniae 83ttactttggt atcgtagata cagccggcat tccaaaacat gacttctatc tctaccaaag 60ccaatgggtt tctgttaaga agaaaccgat ggtacacctt cttcctcact ggaactggga 120aaacaaagaa ttagcatcca aagtagctga ctcagaaggt aagattccag ttcgtgctta 180ttcgaatgct tctagtgtag aattgttctt gaatggaaaa tctcttggtc ttaagacttt 240caataaaaaa caaaccagcg atgggcggac ttaccaagaa ggtgcaaatg ctaatgaact 300ttatcttgaa tggaaagttg cctatcaacc aggtaccttg gaagcaattg ctcgtgatga 360atctggcaag gaaattgctc gagataagat tacgactgct ggtaagccag cggcagttcg 420tcttattaag gaagaccatg cgattgcagc agatggaaaa gacttgactt acatctacta 480tgaaattgtt gacagccagg ggaatgtggt tccaactgct aataatctgg ttcgcttcca 540attgcatggc caaggtcaac tggtcggtgt agataacgga gaacaagcca gccgtgaacg 600ctataaggcg caagcagatg gttcttggat tcgtaaagca tttaatggta aaggtgttgc 660cattgtcaaa tcaactgaac aagcagggaa attcaccctg actgcccact ctgatctctt 720gaaatcgaac caagtcactg tctttactgg taagaaagaa ggacaagaga agactgtttt 780ggggacagaa gtgccaaaag tacagaccat tattggagag gcacctgaaa tgcctaccac 840tgttccgttt gtatacagtg atggtagccg tgcagaacgt cctgtaacct ggtcttcagt 900agatgtgagc aagcctggta ttgtaacggt gaaaggtatg gctgacggac gagaagtaga 960agctcgtgta gaagtgattg ctcttaaatc agagctacca gttgtgaaac gtattgctcc 1020aaatactgac ttgaattctg tagacaaatc tgtttcctat gttttgattg atggaagtgt 1080tgaagagtat gaagtggaca agtgggagat tgccgaagaa gataaagcta agttagcaat 1140tccaggttct cgtattcaag cgaccggtta tttagaaggt caaccaattc atgcaaccct 1200tgtggtagaa gaaggcaatc ctgcggcacc tgcagtacca actgtaacgg ttggtggtga 1260ggcagtaaca ggtcttacta gtcaaaaacc aatgcaatac cgcactcttg cttatggagc 1320taagttgcca gaagtcacag caagtgctaa aaatgcagct gttacagttc ttcaagcaag 1380cgcagcaaac ggcatgcgtg cgagcatctt tattcagcct aaagatggtg gccctcttca 1440aacctatgca attcaattcc ttgaagaagc gccaaaaatt gctcacttga gcttgcaagt 1500ggaaaaagct gacagtctca aagaagacca aactgtcaaa ttgtcggttc gagctcacta 1560tcaagatgga acgcaagctg tattaccagc tgataaagta accttctcta caagtggtga 1620aggggaagtc gcaattcgta aaggaatgct tgagttgcat aagccaggag cagtcactct 1680gaacgctgaa tatgagggag ctaaagacca agttgaactc actatccaag ccaatactga 1740gaagaagatt gcgcaatcca tccgtcctgt aaatgtagtg acagatttgc atcaggaacc 1800aagtcttcca gcaacagtaa cagttgagta tgacaaaggt ttccctaaaa ctcataaagt 1860cacttggcaa gctattccga aagaaaaact agactcctat caaacatttg aagtactagg 1920taaagttgaa ggaattgacc ttgaagcgcg tgcaaaagtc tctgtagaag gtatcgtttc 1980agttgaagaa gtcagtgtga caactccaat cgcagaagca ccacaattac cagaaagtgt 2040tcggacatat gattcaaatg gtcacgtttc atcagctaag gttgcatggg atgcgattcg 2100tccagagcaa tacgctaagg aaggtgtctt tacagttaat ggtcgcttag aaggtacgca 2160attaaca 216784722PRTStreptococcus pneumoniae 84Tyr Phe Gly Ile Val Asp Thr Ala Gly Ile Pro Lys His Asp Phe Tyr1 5 10 15Leu Tyr Gln Ser Gln Trp Val Ser Val Lys Lys Lys Pro Met Val His 20 25 30Leu Leu Pro His Trp Asn Trp Glu Asn Lys Glu Leu Ala Ser Lys Val 35 40 45Ala Asp Ser Glu Gly Lys Ile Pro Val Arg Ala Tyr Ser Asn Ala Ser 50 55 60Ser Val Glu Leu Phe Leu Asn Gly Lys Ser Leu Gly Leu Lys Thr Phe65 70 75 80Asn Lys Lys Gln Thr Ser Asp Gly Arg Thr Tyr Gln Glu Gly Ala Asn 85 90 95Ala Asn Glu Leu Tyr Leu Glu Trp Lys Val Ala Tyr Gln Pro Gly Thr 100 105 110Leu Glu Ala Ile Ala Arg Asp Glu Ser Gly Lys Glu Ile Ala Arg Asp 115 120 125Lys Ile Thr Thr Ala Gly Lys Pro Ala Ala Val Arg Leu Ile Lys Glu 130 135 140Asp His Ala Ile Ala Ala Asp Gly Lys Asp Leu Thr Tyr Ile Tyr Tyr145 150 155 160Glu Ile Val Asp Ser Gln Gly Asn Val Val Pro Thr Ala Asn Asn Leu 165 170 175Val Arg Phe Gln Leu His Gly Gln Gly Gln Leu Val Gly Val Asp Asn 180 185 190Gly Glu Gln Ala Ser Arg Glu Arg Tyr Lys Ala Gln Ala Asp Gly Ser 195 200 205Trp Ile Arg Lys Ala Phe Asn Gly Lys Gly Val Ala Ile Val Lys Ser 210 215 220Thr Glu Gln Ala Gly Lys Phe Thr Leu Thr Ala His Ser Asp Leu Leu225 230 235 240Lys Ser Asn Gln Val Thr Val Phe Thr Gly Lys Lys Glu Gly Gln Glu 245 250 255Lys Thr Val Leu Gly Thr Glu Val Pro Lys Val Gln Thr Ile Ile Gly 260 265 270Glu Ala Pro Glu Met Pro Thr Thr Val Pro Phe Val Tyr Ser Asp Gly 275 280 285Ser Arg Ala Glu Arg Pro Val Thr Trp Ser Ser Val Asp Val Ser Lys 290 295 300Pro Gly Ile Val Thr Val Lys Gly Met Ala Asp Gly Arg Glu Val Glu305 310 315 320Ala Arg Val Glu Val Ile Ala Leu Lys Ser Glu Leu Pro Val Val Lys 325 330 335Arg Ile Ala Pro Asn Thr Asp Leu Asn Ser Val Asp Lys Ser Val Ser 340 345 350Tyr Val Leu Ile Asp Gly Ser Val Glu Glu Tyr Glu Val Asp Lys Trp 355 360 365Glu Ile Ala Glu Glu Asp Lys Ala Lys Leu Ala Ile Pro Gly Ser Arg 370 375 380Ile Gln Ala Thr Gly Tyr Leu Glu Gly Gln Pro Ile His Ala Thr Leu385 390 395 400Val Val Glu Glu Gly Asn Pro Ala Ala Pro Ala Val Pro Thr Val Thr 405 410 415Val Gly Gly Glu Ala Val Thr Gly Leu Thr Ser Gln Lys Pro Met Gln 420 425 430Tyr Arg Thr Leu Ala Tyr Gly Ala Lys Leu Pro Glu Val Thr Ala Ser 435 440 445Ala Lys Asn Ala Ala Val Thr Val Leu Gln Ala Ser Ala Ala Asn Gly 450 455 460Met Arg Ala Ser Ile Phe Ile Gln Pro Lys Asp Gly Gly Pro Leu Gln465 470 475 480Thr Tyr Ala Ile Gln Phe Leu Glu Glu Ala Pro Lys Ile Ala His Leu 485 490 495Ser Leu Gln Val Glu Lys Ala Asp Ser Leu Lys Glu Asp Gln Thr Val 500 505 510Lys Leu Ser Val Arg Ala His Tyr Gln Asp Gly Thr Gln Ala Val Leu 515 520 525Pro Ala Asp Lys Val Thr Phe Ser Thr Ser Gly Glu Gly Glu Val Ala 530 535 540Ile Arg Lys Gly Met Leu Glu Leu His Lys Pro Gly Ala Val Thr Leu545 550 555 560Asn Ala Glu Tyr Glu Gly Ala Lys Asp Gln Val Glu Leu Thr Ile Gln 565 570 575Ala Asn Thr Glu Lys Lys Ile Ala Gln Ser Ile Arg Pro Val Asn Val 580 585 590Val Thr Asp Leu His Gln Glu Pro Ser Leu Pro Ala Thr Val Thr Val 595 600 605Glu Tyr Asp Lys Gly Phe Pro Lys Thr His Lys Val Thr Trp Gln Ala 610 615 620Ile Pro Lys Glu Lys Leu Asp Ser Tyr Gln Thr Phe Glu Val Leu Gly625 630 635 640Lys Val Glu Gly Ile Asp Leu Glu Ala Arg Ala Lys Val Ser Val Glu 645 650 655Gly Ile Val Ser Val Glu Glu Val Ser Val Thr Thr Pro Ile Ala Glu 660 665 670Ala Pro Gln Leu Pro Glu Ser Val Arg Thr Tyr Asp Ser Asn Gly His 675 680 685Val Ser Ser Ala Lys Val Ala Trp Asp Ala Ile Arg Pro Glu Gln Tyr 690 695 700Ala Lys Glu Gly Val Phe Thr Val Asn Gly Arg Leu Glu Gly Thr Gln705 710 715 720Leu Thr852329DNAStreptococcus pneumoniae 85agctaaggtt gcatgggatg cgattcgtcc agagcaatac gctaaggaag gtgtctttac 60agttaatggt cgcttagaag gtacgcaatt aacaactaaa cttcatgttc gcgtatctgc 120tcaaactgag caaggtgcaa acatttctga ccaatggacc ggttcagaat tgccacttgc 180ctttgcttca gactcaaatc caagcgaccc agtttcaaat gttaatgaca agctcatttc 240ctacaataac caaccagcca atcgttggac aaactggaat cgtactaatc cagaagcttc 300agtcggtgtt ctgtttggag attcaggtat cttgagcaaa cgctccgttg ataatctaag 360tgtcggattc catgaagacc atggagttgg tgtaccgaag tcttatgtga ttgagtatta 420tgttggtaag actgtcccaa cagctcctaa aaaccctagt tttgttggta atgaggacca 480tgtctttaat gattctgcca actggaaacc agttactaat ctaaaagccc ctgctcaact 540caaggctgga gaaatgaacc actttagctt tgataaagtt gaaacctatg ctgttcgtat 600tcgcatggtt aaagcagata acaagcgtgg aacgtctatc acagaggtac aaatctttgc 660gaaacaagtt gcggcagcca agcaaggaca aacaagaatc caagttgacg gcaaagactt 720agcaaacttc aaccctgatt tgacagacta ctaccttgag tctgtagatg gaaaagttcc 780ggcagtcaca gcaagtgtta gcaacaatgg tctcgctacc gtcgttccaa gcgttcgtga 840aggtgagcca gttcgtgtca tcgcgaaagc tgaaaatggc gacatcttag gagaataccg 900tctgcacttc actaaggata agagcttact ttctcataaa ccagttgctg cggttaaaca 960agctcgcttg ctacaagtag gtcaagcact tgaattgccg actaaggttc cagtttactt 1020cacaggtaaa gacggctacg aaacaaaaga cctgacagtt gaatgggaag aagttccagc 1080ggaaaatctg acaaaagcag gtcaatttac tgttcgaggc cgtgtccttg gtagtaacct 1140tgttgctgag atcactgtac gagtgacaga caaacttggt gagactcttt cagataaccc 1200taactatgat gaaaacagta accaggcctt tgcttcagca accaatgata ttgacaaaaa 1260ctctcatgac cgcgttgact atctcaatga cggagatcat tcagaaaatc gtcgttggac 1320aaactggtca ccaacaccat cttctaatcc agaagtatca gcgggtgtga ttttccgtga 1380aaatggtaag attgtagaac ggactgttac acaaggaaaa gttcagttct ttgcagatag

1440tggtacggat gcaccatcta aactcgtttt agaacgctat gtcggtccag agtttgaagt 1500gccaacctac tattcaaact accaagccta cgacgcagac catccattca acaatccaga 1560aaattgggaa gctgttcctt atcgtgcgga taaagacatt gcagctggtg atgaaatcaa 1620cgtaacattt aaagctatca aagccaaagc tatgagatgg cgtatggagc gtaaagcaga 1680taagagcggt gttgcgatga ttgagatgac cttccttgca ccaagtgaat tgcctcaaga 1740aagcactcaa tcaaagattc ttgtagatgg aaaagaactt gctgatttcg ctgaaaatcg 1800tcaagactat caaattacct ataaaggtca acggccaaaa gtctcagttg aagaaaacaa 1860tcaagtagct tcaactgtgg tagatagtgg agaagatagc tttccagtac ttgttcgcct 1920cgtttcagaa agtggaaaac aagtcaagga ataccgtatc cacttgacta aggaaaaacc 1980agtttctgag aagacagttg ctgctgtaca agaagatctt ccaaaaatcg aatttgttga 2040aaaagatttg gcatacaaga cagttgagaa aaaagattca acactgtatc taggtgaaac 2100tcgtgtagaa caagaaggaa aagttggaaa agaacgtatc tttacagcga ttaatcctga 2160tggaagtaag gaagaaaaac tccgtgaagt ggtagaagtt ccgacagacc gcatcgtctt 2220ggttggaacc aaaccagtag ctcaagaagc taaaaaacca caagtgtcag aaaaagcaga 2280tacaaaacca attgattcaa gtgaagctag tcaaactaat aaagcccag 232986776PRTStreptococcus pneumoniae 86Ala Lys Val Ala Trp Asp Ala Ile Arg Pro Glu Gln Tyr Ala Lys Glu1 5 10 15Gly Val Phe Thr Val Asn Gly Arg Leu Glu Gly Thr Gln Leu Thr Thr 20 25 30Lys Leu His Val Arg Val Ser Ala Gln Thr Glu Gln Gly Ala Asn Ile 35 40 45Ser Asp Gln Trp Thr Gly Ser Glu Leu Pro Leu Ala Phe Ala Ser Asp 50 55 60Ser Asn Pro Ser Asp Pro Val Ser Asn Val Asn Asp Lys Leu Ile Ser65 70 75 80Tyr Asn Asn Gln Pro Ala Asn Arg Trp Thr Asn Trp Asn Arg Thr Asn 85 90 95Pro Glu Ala Ser Val Gly Val Leu Phe Gly Asp Ser Gly Ile Leu Ser 100 105 110Lys Arg Ser Val Asp Asn Leu Ser Val Gly Phe His Glu Asp His Gly 115 120 125Val Gly Val Pro Lys Ser Tyr Val Ile Glu Tyr Tyr Val Gly Lys Thr 130 135 140Val Pro Thr Ala Pro Lys Asn Pro Ser Phe Val Gly Asn Glu Asp His145 150 155 160Val Phe Asn Asp Ser Ala Asn Trp Lys Pro Val Thr Asn Leu Lys Ala 165 170 175Pro Ala Gln Leu Lys Ala Gly Glu Met Asn His Phe Ser Phe Asp Lys 180 185 190Val Glu Thr Tyr Ala Val Arg Ile Arg Met Val Lys Ala Asp Asn Lys 195 200 205Arg Gly Thr Ser Ile Thr Glu Val Gln Ile Phe Ala Lys Gln Val Ala 210 215 220Ala Ala Lys Gln Gly Gln Thr Arg Ile Gln Val Asp Gly Lys Asp Leu225 230 235 240Ala Asn Phe Asn Pro Asp Leu Thr Asp Tyr Tyr Leu Glu Ser Val Asp 245 250 255Gly Lys Val Pro Ala Val Thr Ala Ser Val Ser Asn Asn Gly Leu Ala 260 265 270Thr Val Val Pro Ser Val Arg Glu Gly Glu Pro Val Arg Val Ile Ala 275 280 285Lys Ala Glu Asn Gly Asp Ile Leu Gly Glu Tyr Arg Leu His Phe Thr 290 295 300Lys Asp Lys Ser Leu Leu Ser His Lys Pro Val Ala Ala Val Lys Gln305 310 315 320Ala Arg Leu Leu Gln Val Gly Gln Ala Leu Glu Leu Pro Thr Lys Val 325 330 335Pro Val Tyr Phe Thr Gly Lys Asp Gly Tyr Glu Thr Lys Asp Leu Thr 340 345 350Val Glu Trp Glu Glu Val Pro Ala Glu Asn Leu Thr Lys Ala Gly Gln 355 360 365Phe Thr Val Arg Gly Arg Val Leu Gly Ser Asn Leu Val Ala Glu Ile 370 375 380Thr Val Arg Val Thr Asp Lys Leu Gly Glu Thr Leu Ser Asp Asn Pro385 390 395 400Asn Tyr Asp Glu Asn Ser Asn Gln Ala Phe Ala Ser Ala Thr Asn Asp 405 410 415Ile Asp Lys Asn Ser His Asp Arg Val Asp Tyr Leu Asn Asp Gly Asp 420 425 430His Ser Glu Asn Arg Arg Trp Thr Asn Trp Ser Pro Thr Pro Ser Ser 435 440 445Asn Pro Glu Val Ser Ala Gly Val Ile Phe Arg Glu Asn Gly Lys Ile 450 455 460Val Glu Arg Thr Val Thr Gln Gly Lys Val Gln Phe Phe Ala Asp Ser465 470 475 480Gly Thr Asp Ala Pro Ser Lys Leu Val Leu Glu Arg Tyr Val Gly Pro 485 490 495Glu Phe Glu Val Pro Thr Tyr Tyr Ser Asn Tyr Gln Ala Tyr Asp Ala 500 505 510Asp His Pro Phe Asn Asn Pro Glu Asn Trp Glu Ala Val Pro Tyr Arg 515 520 525Ala Asp Lys Asp Ile Ala Ala Gly Asp Glu Ile Asn Val Thr Phe Lys 530 535 540Ala Ile Lys Ala Lys Ala Met Arg Trp Arg Met Glu Arg Lys Ala Asp545 550 555 560Lys Ser Gly Val Ala Met Ile Glu Met Thr Phe Leu Ala Pro Ser Glu 565 570 575Leu Pro Gln Glu Ser Thr Gln Ser Lys Ile Leu Val Asp Gly Lys Glu 580 585 590Leu Ala Asp Phe Ala Glu Asn Arg Gln Asp Tyr Gln Ile Thr Tyr Lys 595 600 605Gly Gln Arg Pro Lys Val Ser Val Glu Glu Asn Asn Gln Val Ala Ser 610 615 620Thr Val Val Asp Ser Gly Glu Asp Ser Phe Pro Val Leu Val Arg Leu625 630 635 640Val Ser Glu Ser Gly Lys Gln Val Lys Glu Tyr Arg Ile His Leu Thr 645 650 655Lys Glu Lys Pro Val Ser Glu Lys Thr Val Ala Ala Val Gln Glu Asp 660 665 670Leu Pro Lys Ile Glu Phe Val Glu Lys Asp Leu Ala Tyr Lys Thr Val 675 680 685Glu Lys Lys Asp Ser Thr Leu Tyr Leu Gly Glu Thr Arg Val Glu Gln 690 695 700Glu Gly Lys Val Gly Lys Glu Arg Ile Phe Thr Ala Ile Asn Pro Asp705 710 715 720Gly Ser Lys Glu Glu Lys Leu Arg Glu Val Val Glu Val Pro Thr Asp 725 730 735Arg Ile Val Leu Val Gly Thr Lys Pro Val Ala Gln Glu Ala Lys Lys 740 745 750Pro Gln Val Ser Glu Lys Ala Asp Thr Lys Pro Ile Asp Ser Ser Glu 755 760 765Ala Ser Gln Thr Asn Lys Ala Gln 770 77587133DNAStreptococcus pneumoniae 87ctatcactat gtaaataaag agattatttc acaagaagct aaagatttaa ttcagacagg 60aaagcctgac aggaatgaag ttgtatatgg tttggtgtat caaaaagatc agttgcctca 120aacagggaca gaa 1338844PRTStreptococcus pneumoniae 88Tyr His Tyr Val Asn Lys Glu Ile Ile Ser Gln Glu Ala Lys Asp Leu1 5 10 15Ile Gln Thr Gly Lys Pro Asp Arg Asn Glu Val Val Tyr Gly Leu Val 20 25 30Tyr Gln Lys Asp Gln Leu Pro Gln Thr Gly Thr Glu 35 4089775DNAStreptococcus pneumoniae 89tgagactcct caatcaataa caaatcagga gcaagctagg acagaaaacc aagtagtaga 60gacagaggaa gctccaaaag aagaagcacc taaaacagaa gaaagtccaa aggaagaacc 120aaaatcggag gtaaaaccta ctgacgacac ccttcctaaa gtagaagagg ggaaagaaga 180ttcagcagaa ccagctccag ttgaagaagt aggtggagaa gttgagtcaa aaccagagga 240aaaagtagca gttaagccag aaagtcaacc atcagacaaa ccagctgagg aatcaaaagt 300tgaacaagca ggtgaaccag tcgcgccaag agaagacgaa aaggcaccag tcgagccaga 360aaagcaacca gaagctcctg aagaagagaa ggctgtagag gaaacaccga aacaagaaga 420gtcaactcca gataccaagg ctgaagaaac tgtagaacca aaagaggaga ctgttaatca 480atctattgaa caaccaaaag ttgaaacgcc tgctgtagaa aaacaaacag aaccaacaga 540ggaaccaaaa gttgaacaag caggtgaacc agtcgcgcca agagaagacg aacaggcacc 600aacggcacca gttgagccag aaaagcaacc agaagttcct gaagaagaga aggctgtaga 660ggaaacaccg aaaccagaag ataaaataaa gggtattggt actaaagaac cagttgataa 720aagtgagtta aataatcaaa ttgataaagc tagttcagtt tctcctactg attat 77590258PRTStreptococcus pneumoniae 90Glu Thr Pro Gln Ser Ile Thr Asn Gln Glu Gln Ala Arg Thr Glu Asn1 5 10 15Gln Val Val Glu Thr Glu Glu Ala Pro Lys Glu Glu Ala Pro Lys Thr 20 25 30Glu Glu Ser Pro Lys Glu Glu Pro Lys Ser Glu Val Lys Pro Thr Asp 35 40 45Asp Thr Leu Pro Lys Val Glu Glu Gly Lys Glu Asp Ser Ala Glu Pro 50 55 60Ala Pro Val Glu Glu Val Gly Gly Glu Val Glu Ser Lys Pro Glu Glu65 70 75 80Lys Val Ala Val Lys Pro Glu Ser Gln Pro Ser Asp Lys Pro Ala Glu 85 90 95Glu Ser Lys Val Glu Gln Ala Gly Glu Pro Val Ala Pro Arg Glu Asp 100 105 110Glu Lys Ala Pro Val Glu Pro Glu Lys Gln Pro Glu Ala Pro Glu Glu 115 120 125Glu Lys Ala Val Glu Glu Thr Pro Lys Gln Glu Glu Ser Thr Pro Asp 130 135 140Thr Lys Ala Glu Glu Thr Val Glu Pro Lys Glu Glu Thr Val Asn Gln145 150 155 160Ser Ile Glu Gln Pro Lys Val Glu Thr Pro Ala Val Glu Lys Gln Thr 165 170 175Glu Pro Thr Glu Glu Pro Lys Val Glu Gln Ala Gly Glu Pro Val Ala 180 185 190Pro Arg Glu Asp Glu Gln Ala Pro Thr Ala Pro Val Glu Pro Glu Lys 195 200 205Gln Pro Glu Val Pro Glu Glu Glu Lys Ala Val Glu Glu Thr Pro Lys 210 215 220Pro Glu Asp Lys Ile Lys Gly Ile Gly Thr Lys Glu Pro Val Asp Lys225 230 235 240Ser Glu Leu Asn Asn Gln Ile Asp Lys Ala Ser Ser Val Ser Pro Thr 245 250 255Asp Tyr91199DNAStreptococcus pneumoniae 91ggatgctcaa gaaactgcgg gagttcacta taaatatgtg gcagattcag agctatcatc 60agaagaaaag aagcagcttg tctatgatat tccgacatac gtggagaatg atgatgaaac 120ttattatctt gtttataagt taaattctca aaatcaactg gcggaattgc caaatactgg 180aagcaagaat gagaggcaa 1999266PRTStreptococcus pneumoniae 92Asp Ala Gln Glu Thr Ala Gly Val His Tyr Lys Tyr Val Ala Asp Ser1 5 10 15Glu Leu Ser Ser Glu Glu Lys Lys Gln Leu Val Tyr Asp Ile Pro Thr 20 25 30Tyr Val Glu Asn Asp Asp Glu Thr Tyr Tyr Leu Val Tyr Lys Leu Asn 35 40 45Ser Gln Asn Gln Leu Ala Glu Leu Pro Asn Thr Gly Ser Lys Asn Glu 50 55 60Arg Gln6593835DNAStreptococcus pneumoniae 93cgacaaaggt gagactgagg ttcaaccaga gtcgccagat actgtggtaa gtgataaagg 60tgaaccagag caggtagcac cgcttccaga atataagggt aatattgagc aagtaaaacc 120tgaaactccg gttgagaaga ccaaagaaca aggtccagaa aaaactgaag aagttccagt 180aaaaccaaca gaagaaacac cagtaaatcc aaatgaaggt actacagaag gaacctcaat 240tcaagaagca gaaaatccag ttcaacctgc agaagaatca acaacgaatt cagagaaagt 300atcaccagat acatctagca aaaatactgg ggaagtgtcc agtaatccta gtgattcgac 360aacctcagtt ggagaatcaa ataaaccaga acataatgac tctaaaaatg aaaattcaga 420aaaaactgta gaagaagttc cagtaaatcc aaatgaaggc acagtagaag gtacctcaaa 480tcaagaaaca gaaaaaccag ttcaacctgc agaagaaaca caaacaaact ctgggaaaat 540agctaacgaa aatactggag aagtatccaa taaacctagt gattcaaaac caccagttga 600agaatcaaat caaccagaaa aaaacggaac tgcaacaaaa ccagaaaatt caggtaatac 660aacatcagag aatggacaaa cagaaccaga accatcaaac ggaaattcaa ctgaggatgt 720ttcaaccgaa tcaaacacat ccaattcaaa tggaaacgaa gaaattaaac aagaaaatga 780actagaccct gataaaaagg tagaagaacc agagaaaaca cttgaattaa gaaat 83594278PRTStreptococcus pneumoniae 94Asp Lys Gly Glu Thr Glu Val Gln Pro Glu Ser Pro Asp Thr Val Val1 5 10 15Ser Asp Lys Gly Glu Pro Glu Gln Val Ala Pro Leu Pro Glu Tyr Lys 20 25 30Gly Asn Ile Glu Gln Val Lys Pro Glu Thr Pro Val Glu Lys Thr Lys 35 40 45Glu Gln Gly Pro Glu Lys Thr Glu Glu Val Pro Val Lys Pro Thr Glu 50 55 60Glu Thr Pro Val Asn Pro Asn Glu Gly Thr Thr Glu Gly Thr Ser Ile65 70 75 80Gln Glu Ala Glu Asn Pro Val Gln Pro Ala Glu Glu Ser Thr Thr Asn 85 90 95Ser Glu Lys Val Ser Pro Asp Thr Ser Ser Lys Asn Thr Gly Glu Val 100 105 110Ser Ser Asn Pro Ser Asp Ser Thr Thr Ser Val Gly Glu Ser Asn Lys 115 120 125Pro Glu His Asn Asp Ser Lys Asn Glu Asn Ser Glu Lys Thr Val Glu 130 135 140Glu Val Pro Val Asn Pro Asn Glu Gly Thr Val Glu Gly Thr Ser Asn145 150 155 160Gln Glu Thr Glu Lys Pro Val Gln Pro Ala Glu Glu Thr Gln Thr Asn 165 170 175Ser Gly Lys Ile Ala Asn Glu Asn Thr Gly Glu Val Ser Asn Lys Pro 180 185 190Ser Asp Ser Lys Pro Pro Val Glu Glu Ser Asn Gln Pro Glu Lys Asn 195 200 205Gly Thr Ala Thr Lys Pro Glu Asn Ser Gly Asn Thr Thr Ser Glu Asn 210 215 220Gly Gln Thr Glu Pro Glu Pro Ser Asn Gly Asn Ser Thr Glu Asp Val225 230 235 240Ser Thr Glu Ser Asn Thr Ser Asn Ser Asn Gly Asn Glu Glu Ile Lys 245 250 255Gln Glu Asn Glu Leu Asp Pro Asp Lys Lys Val Glu Glu Pro Glu Lys 260 265 270Thr Leu Glu Leu Arg Asn 27595709DNAStreptococcus pneumoniae 95aaatcaattg gtagcacaag atccaaaagc acaagatagc actaaactga ctgctgaaaa 60atcaactgtt aaagcacctg ctcaaagagt agatgtaaaa gatataactc atttaacaga 120tgaagaaaaa gttaaggttg ctattttaca agcaaatggt tcagcattag acggagcgac 180aatcaatgta gctggagatg gtacagcaac aatcacattc ccagatggtt cagtagtgac 240gattctagga aaagatacag ttcaacaatc tgcgaaaggt gaatctgtaa ctcaagaagc 300tacaccagag tataagctag aaaatacacc aggtggagat aagggaggca atactggaag 360ctcagatgct aatgcgaatg aaggcggtgg tagccaggcg ggtggatcag ctcacacagg 420ttcacaaaac tcagctcaat cacaagcttc taagcaatta gctactgaaa aagaatcagc 480taaaaatgcc attgaaaaag cagccaagga caagcaggat gaaatcaaag gcgcaccgct 540ttctgataaa gaaaaagcag aacttttagc aagagtggaa gcagaaaaac aagcagctct 600caaagagatt gaaaatgcga aaactatgga agatgtgaag gaagcagaaa cgattggagt 660gcaagccatt gccatggtta cagttcctaa gagaccagtg gctcctaat 70996236PRTStreptococcus pneumoniae 96Asn Gln Leu Val Ala Gln Asp Pro Lys Ala Gln Asp Ser Thr Lys Leu1 5 10 15Thr Ala Glu Lys Ser Thr Val Lys Ala Pro Ala Gln Arg Val Asp Val 20 25 30Lys Asp Ile Thr His Leu Thr Asp Glu Glu Lys Val Lys Val Ala Ile 35 40 45Leu Gln Ala Asn Gly Ser Ala Leu Asp Gly Ala Thr Ile Asn Val Ala 50 55 60Gly Asp Gly Thr Ala Thr Ile Thr Phe Pro Asp Gly Ser Val Val Thr65 70 75 80Ile Leu Gly Lys Asp Thr Val Gln Gln Ser Ala Lys Gly Glu Ser Val 85 90 95Thr Gln Glu Ala Thr Pro Glu Tyr Lys Leu Glu Asn Thr Pro Gly Gly 100 105 110Asp Lys Gly Gly Asn Thr Gly Ser Ser Asp Ala Asn Ala Asn Glu Gly 115 120 125Gly Gly Ser Gln Ala Gly Gly Ser Ala His Thr Gly Ser Gln Asn Ser 130 135 140Ala Gln Ser Gln Ala Ser Lys Gln Leu Ala Thr Glu Lys Glu Ser Ala145 150 155 160Lys Asn Ala Ile Glu Lys Ala Ala Lys Asp Lys Gln Asp Glu Ile Lys 165 170 175Gly Ala Pro Leu Ser Asp Lys Glu Lys Ala Glu Leu Leu Ala Arg Val 180 185 190Glu Ala Glu Lys Gln Ala Ala Leu Lys Glu Ile Glu Asn Ala Lys Thr 195 200 205Met Glu Asp Val Lys Glu Ala Glu Thr Ile Gly Val Gln Ala Ile Ala 210 215 220Met Val Thr Val Pro Lys Arg Pro Val Ala Pro Asn225 230 23597787DNAStreptococcus pneumoniae 97caaacagtca gcttcaggaa cgattgaggt gatttcacga gaaaatggct ctgggacacg 60gggtgccttc acagaaatca cagggattct caaaaaagac ggtgataaaa aaattgacaa 120cactgccaaa acagctgtga ttcaaaatag tacagaaggt gttctctcag cagttcaagg 180gaatgctaat gctatcggct acatctcctt gggatcttta acgaaatctg tcaaggcttt 240agagattgat ggtgtcaagg ctagtcgaga cacagtttta gatggtgaat accctcttca 300acgtcccttc aacattgttt ggtcttctaa tctttccaag ctaggtcaag attttatcag 360ctttatccac tccaaacaag gtcaacaagt ggtcacagat aataaattta ttgaagctaa 420aaccgaaacc acggaatata caagccaaca cttatcaggc aagttgtctg ttgtaggttc 480cacttcagta tcttctttaa tggaaaaatt agcagaagct tataaaaaag aaaatccaga 540agttacgatt gatattacct ctaatgggtc ttcagcaggt attaccgctg ttaaggagaa 600aaccgctgat attggtatgg tttctaggga attaactcct gaagaaggta agagtctcac 660ccatgatgct attgctttag acggtattgc tgttgtggtc aataatgaca ataaggcaag 720ccaagtcagt atggctgaac ttgcagacgt ttttagtggc aaattaacca cctgggacaa 780gattaaa 78798262PRTStreptococcus pneumoniae 98Lys Gln Ser Ala Ser Gly Thr Ile Glu Val Ile Ser Arg Glu Asn Gly1 5 10 15Ser Gly Thr Arg Gly Ala Phe Thr Glu Ile Thr Gly

Ile Leu Lys Lys 20 25 30Asp Gly Asp Lys Lys Ile Asp Asn Thr Ala Lys Thr Ala Val Ile Gln 35 40 45Asn Ser Thr Glu Gly Val Leu Ser Ala Val Gln Gly Asn Ala Asn Ala 50 55 60Ile Gly Tyr Ile Ser Leu Gly Ser Leu Thr Lys Ser Val Lys Ala Leu65 70 75 80Glu Ile Asp Gly Val Lys Ala Ser Arg Asp Thr Val Leu Asp Gly Glu 85 90 95Tyr Pro Leu Gln Arg Pro Phe Asn Ile Val Trp Ser Ser Asn Leu Ser 100 105 110Lys Leu Gly Gln Asp Phe Ile Ser Phe Ile His Ser Lys Gln Gly Gln 115 120 125Gln Val Val Thr Asp Asn Lys Phe Ile Glu Ala Lys Thr Glu Thr Thr 130 135 140Glu Tyr Thr Ser Gln His Leu Ser Gly Lys Leu Ser Val Val Gly Ser145 150 155 160Thr Ser Val Ser Ser Leu Met Glu Lys Leu Ala Glu Ala Tyr Lys Lys 165 170 175Glu Asn Pro Glu Val Thr Ile Asp Ile Thr Ser Asn Gly Ser Ser Ala 180 185 190Gly Ile Thr Ala Val Lys Glu Lys Thr Ala Asp Ile Gly Met Val Ser 195 200 205Arg Glu Leu Thr Pro Glu Glu Gly Lys Ser Leu Thr His Asp Ala Ile 210 215 220Ala Leu Asp Gly Ile Ala Val Val Val Asn Asn Asp Asn Lys Ala Ser225 230 235 240Gln Val Ser Met Ala Glu Leu Ala Asp Val Phe Ser Gly Lys Leu Thr 245 250 255Thr Trp Asp Lys Ile Lys 26099421DNAStreptococcus pneumoniae 99attcgatgat gcggatgaaa agatgacccg tgatgaaatt gcctatatgc tgacaaatag 60tgaagaaaca ttggatgctg atgagattga gatgctacaa ggtgtctttt cgctcgatga 120actgatggca cgagaggtta tggttcctcg aacggatgcc tttatggtgg atattcagga 180tgatagtcaa gccattatcc aaagtatttt aaaacaaaat tattctcgta tcccggttta 240tgatggggat aaggacaatg taattggaat cattcacacc aagagtctcc ttaaggcagg 300ctttgtggac ggttttgaca atattgtttg gaagagaatt ttacaagatc cactttttgt 360acctgaaact atttttgtgg atgacttgct aaaagaactg cgaaataccc aaagacaaat 420g 421100140PRTStreptococcus pneumoniae 100Phe Asp Asp Ala Asp Glu Lys Met Thr Arg Asp Glu Ile Ala Tyr Met1 5 10 15Leu Thr Asn Ser Glu Glu Thr Leu Asp Ala Asp Glu Ile Glu Met Leu 20 25 30Gln Gly Val Phe Ser Leu Asp Glu Leu Met Ala Arg Glu Val Met Val 35 40 45Pro Arg Thr Asp Ala Phe Met Val Asp Ile Gln Asp Asp Ser Gln Ala 50 55 60Ile Ile Gln Ser Ile Leu Lys Gln Asn Tyr Ser Arg Ile Pro Val Tyr65 70 75 80Asp Gly Asp Lys Asp Asn Val Ile Gly Ile Ile His Thr Lys Ser Leu 85 90 95Leu Lys Ala Gly Phe Val Asp Gly Phe Asp Asn Ile Val Trp Lys Arg 100 105 110Ile Leu Gln Asp Pro Leu Phe Val Pro Glu Thr Ile Phe Val Asp Asp 115 120 125Leu Leu Lys Glu Leu Arg Asn Thr Gln Arg Gln Met 130 135 140101331DNAStreptococcus pneumoniae 101ggagagtcga tcaaaagtag atgaagctgt gtctaagttt gaaaaggact catcttcttc 60gtcaagttca gactcttcca ctaaaccgga agcttcagat acagcgaagc caaacaagcc 120gacagaacca ggagaaaagg tagcagaagc taagaagaag gttgaagaag ctgagaaaaa 180agccaaggat caaaaagaag aagatcgtcg taactaccca accattactt acaaaacgct 240tgaacttgaa attgctgagt ccgatgtgga agttaaaaaa gcggagcttg aactagtaaa 300agtgaaagct aacgaacctc gagacgagca a 331102110PRTStreptococcus pneumoniae 102Glu Ser Arg Ser Lys Val Asp Glu Ala Val Ser Lys Phe Glu Lys Asp1 5 10 15Ser Ser Ser Ser Ser Ser Ser Asp Ser Ser Thr Lys Pro Glu Ala Ser 20 25 30Asp Thr Ala Lys Pro Asn Lys Pro Thr Glu Pro Gly Glu Lys Val Ala 35 40 45Glu Ala Lys Lys Lys Val Glu Glu Ala Glu Lys Lys Ala Lys Asp Gln 50 55 60Lys Glu Glu Asp Arg Arg Asn Tyr Pro Thr Ile Thr Tyr Lys Thr Leu65 70 75 80Glu Leu Glu Ile Ala Glu Ser Asp Val Glu Val Lys Lys Ala Glu Leu 85 90 95Glu Leu Val Lys Val Lys Ala Asn Glu Pro Arg Asp Glu Gln 100 105 110103358DNAStreptococcus pneumoniae 103atggacaaca ggaaactggg acgaggttat atctggtaag attgacaagt acaaagatcc 60agatattcca acagttgaat cacaagaagt tacgtcagac tctagtgata aagaaataac 120ggtaaggtat gaccgtttat caacaccaga aaaaccaatc ccacaaccaa atccagagca 180tccaagtgtt ccgacaccaa acccagaact accaaatcaa gagactccaa caccagataa 240accaactcca gaaccaggta ctccaaaaac tgaaactcca gtgaatccag acccagaagt 300tccgacttat gagacaggta agagagagga attgccaaac acaggtacag aagctaat 358104119PRTStreptococcus pneumoniae 104Trp Thr Thr Gly Asn Trp Asp Glu Val Ile Ser Gly Lys Ile Asp Lys1 5 10 15Tyr Lys Asp Pro Asp Ile Pro Thr Val Glu Ser Gln Glu Val Thr Ser 20 25 30Asp Ser Ser Asp Lys Glu Ile Thr Val Arg Tyr Asp Arg Leu Ser Thr 35 40 45Pro Glu Lys Pro Ile Pro Gln Pro Asn Pro Glu His Pro Ser Val Pro 50 55 60Thr Pro Asn Pro Glu Leu Pro Asn Gln Glu Thr Pro Thr Pro Asp Lys65 70 75 80Pro Thr Pro Glu Pro Gly Thr Pro Lys Thr Glu Thr Pro Val Asn Pro 85 90 95Asp Pro Glu Val Pro Thr Tyr Glu Thr Gly Lys Arg Glu Glu Leu Pro 100 105 110Asn Thr Gly Thr Glu Ala Asn 1151051879DNAStreptococcus pneumoniaemisc_feature(1040)..(1040)n is a, c, g, or t 105cgatgggctc aatccaaccc caggtcaagt cttacctgaa gagacatcgg gaacgaaaga 60gggtgactta tcagaaaaac caggagacac cgttctcact caagcgaaac ctgagggcgt 120tactggaaat acgaattcac ttccgacacc tacagaaaga actgaagtga gcgaggaaac 180aagcccttct agtctggata cactttttga aaaagatgaa gaagctcaaa aaaatccaga 240gctaacagat gtcttaaaag aaactgtaga tacagctgat gtggatggga cacaagcaag 300tccagcagaa actactcctg aacaagtaaa aggtggagtg aaagaaaata caaaagacag 360catcgatgtt cctgctgctt atcttgaaaa agctgaaggg aaaggtcctt tcactgccgg 420tgtaaaccaa gtaattcctt atgaactatt cgctggtgat ggtatgttaa ctcgtctatt 480actaaaagct tcggataatg ctccttggtc tgacaatggt actgctaaaa atcctgcttt 540acctcctctt gaaggattaa caaaagggaa atacttctat gaagtagact taaatggcaa 600tactgttggt aaacaaggtc aagctttaat tgatcaactt cgcgctaatg gtactcaaac 660ttataaagct actgttaaag tttacggaaa taaagacggt aaagctgact tgactaatct 720agttgctact aaaaatgtag acatcaacat caatggatta gttgctaaag aaacagttca 780aaaagccgtt gcagacaacg ttaaagacag tatcgatgtt ccagcagcct acctagaaaa 840agccaagggt gaaggtccat tcacagcagg tgtcaaccat gtgattccat acgaactctt 900cgcaggtgat ggcatgttga ctcgtctctt gctcaaggca tctgacaagg caccatggtc 960agataacggc gacgctaaaa acccagccct atctccacta ggcgaaaacg tgaagaccaa 1020aggtcaatac ttctatcaan tagccttgga cggaaatgta gctggcaaag aaaaacaagc 1080gctcattgac cagttccgag caaanggtac tcaaacttac agcgctacag tcaatgtcta 1140tggtaacaaa gacggtaaac cagacttgga caacatcgta gcaactaaaa aagtcactat 1200taacataaac ggtttaattt ctaaagaaac agttcaaaaa gccgttgcag acaacgttaa 1260ngacagtatc gatgttccag cagcctacct agaaaaagcc aagggtgaag gtccattcac 1320agcaggtgtc aaccatgtga ttccatacga actcttcgca ggtgatggta tgttgactcg 1380tctcttgctc aaggcatctg acaaggcacc atggtcagat aacggngacg ctaaaaaccc 1440agcnctatct ccactaggtg aaaacgtgaa gaccaaaggt caatacttct atcaantagc 1500cttggacgga aatgtagctg gcaaagaaaa acaagcgctc attgaccagt tccgagcaaa 1560cggtactcaa acttacagcg ctacagtcaa tgtctatggt aacaaagacg gtaaaccaga 1620cttggacaac atcgtagcaa ctaaaaaagt cactattaag ataaatgtta aagaaacatc 1680agacacagca aatggttcat tatcaccttc taactctggt tctggcgtga ctccgatgaa 1740tcacaatcat gctacaggta ctacagatag catgcctgct gacaccatga caagttctac 1800caacacgatg gcaggtgaaa acatggctgc ttctgctaac aagatgtctg atacgatgat 1860gtcagaggat aaagctatg 1879106626PRTStreptococcus pneumoniaeSITE(347)..(347)Xaa can be any naturally occurring amino acid 106Asp Gly Leu Asn Pro Thr Pro Gly Gln Val Leu Pro Glu Glu Thr Ser1 5 10 15Gly Thr Lys Glu Gly Asp Leu Ser Glu Lys Pro Gly Asp Thr Val Leu 20 25 30Thr Gln Ala Lys Pro Glu Gly Val Thr Gly Asn Thr Asn Ser Leu Pro 35 40 45Thr Pro Thr Glu Arg Thr Glu Val Ser Glu Glu Thr Ser Pro Ser Ser 50 55 60Leu Asp Thr Leu Phe Glu Lys Asp Glu Glu Ala Gln Lys Asn Pro Glu65 70 75 80Leu Thr Asp Val Leu Lys Glu Thr Val Asp Thr Ala Asp Val Asp Gly 85 90 95Thr Gln Ala Ser Pro Ala Glu Thr Thr Pro Glu Gln Val Lys Gly Gly 100 105 110Val Lys Glu Asn Thr Lys Asp Ser Ile Asp Val Pro Ala Ala Tyr Leu 115 120 125Glu Lys Ala Glu Gly Lys Gly Pro Phe Thr Ala Gly Val Asn Gln Val 130 135 140Ile Pro Tyr Glu Leu Phe Ala Gly Asp Gly Met Leu Thr Arg Leu Leu145 150 155 160Leu Lys Ala Ser Asp Asn Ala Pro Trp Ser Asp Asn Gly Thr Ala Lys 165 170 175Asn Pro Ala Leu Pro Pro Leu Glu Gly Leu Thr Lys Gly Lys Tyr Phe 180 185 190Tyr Glu Val Asp Leu Asn Gly Asn Thr Val Gly Lys Gln Gly Gln Ala 195 200 205Leu Ile Asp Gln Leu Arg Ala Asn Gly Thr Gln Thr Tyr Lys Ala Thr 210 215 220Val Lys Val Tyr Gly Asn Lys Asp Gly Lys Ala Asp Leu Thr Asn Leu225 230 235 240Val Ala Thr Lys Asn Val Asp Ile Asn Ile Asn Gly Leu Val Ala Lys 245 250 255Glu Thr Val Gln Lys Ala Val Ala Asp Asn Val Lys Asp Ser Ile Asp 260 265 270Val Pro Ala Ala Tyr Leu Glu Lys Ala Lys Gly Glu Gly Pro Phe Thr 275 280 285Ala Gly Val Asn His Val Ile Pro Tyr Glu Leu Phe Ala Gly Asp Gly 290 295 300Met Leu Thr Arg Leu Leu Leu Lys Ala Ser Asp Lys Ala Pro Trp Ser305 310 315 320Asp Asn Gly Asp Ala Lys Asn Pro Ala Leu Ser Pro Leu Gly Glu Asn 325 330 335Val Lys Thr Lys Gly Gln Tyr Phe Tyr Gln Xaa Ala Leu Asp Gly Asn 340 345 350Val Ala Gly Lys Glu Lys Gln Ala Leu Ile Asp Gln Phe Arg Ala Xaa 355 360 365Gly Thr Gln Thr Tyr Ser Ala Thr Val Asn Val Tyr Gly Asn Lys Asp 370 375 380Gly Lys Pro Asp Leu Asp Asn Ile Val Ala Thr Lys Lys Val Thr Ile385 390 395 400Asn Ile Asn Gly Leu Ile Ser Lys Glu Thr Val Gln Lys Ala Val Ala 405 410 415Asp Asn Val Xaa Asp Ser Ile Asp Val Pro Ala Ala Tyr Leu Glu Lys 420 425 430Ala Lys Gly Glu Gly Pro Phe Thr Ala Gly Val Asn His Val Ile Pro 435 440 445Tyr Glu Leu Phe Ala Gly Asp Gly Met Leu Thr Arg Leu Leu Leu Lys 450 455 460Ala Ser Asp Lys Ala Pro Trp Ser Asp Asn Gly Asp Ala Lys Asn Pro465 470 475 480Ala Leu Ser Pro Leu Gly Glu Asn Val Lys Thr Lys Gly Gln Tyr Phe 485 490 495Tyr Gln Xaa Ala Leu Asp Gly Asn Val Ala Gly Lys Glu Lys Gln Ala 500 505 510Leu Ile Asp Gln Phe Arg Ala Asn Gly Thr Gln Thr Tyr Ser Ala Thr 515 520 525Val Asn Val Tyr Gly Asn Lys Asp Gly Lys Pro Asp Leu Asp Asn Ile 530 535 540Val Ala Thr Lys Lys Val Thr Ile Lys Ile Asn Val Lys Glu Thr Ser545 550 555 560Asp Thr Ala Asn Gly Ser Leu Ser Pro Ser Asn Ser Gly Ser Gly Val 565 570 575Thr Pro Met Asn His Asn His Ala Thr Gly Thr Thr Asp Ser Met Pro 580 585 590Ala Asp Thr Met Thr Ser Ser Thr Asn Thr Met Ala Gly Glu Asn Met 595 600 605Ala Ala Ser Ala Asn Lys Met Ser Asp Thr Met Met Ser Glu Asp Lys 610 615 620Ala Met625107593DNAStreptococcus pneumoniae 107ttccaatcaa aaacaggcag atggtaaact caatatcgtg acaacctttt accctgtcta 60tgartttacc aagcaagtcg caggagatac ggctaatgta gaactcctaa tcggtgctgg 120gacagaacct catgaatacg aaccatctgc caaggcagtt gccaaaatcc aagatgcaga 180taccttcgtt tatgaaaatg aaaacatgga aacatgggta cctaaattgc tagatacctt 240ggataagaaa aaagtgaaaa ccatcaaggc gacaggcgat atgttgctct tgccaggtgg 300cgaggaagaa gagggagacc atgaccatgg agaagaaggt catcaccatg agtttgaccc 360ccatgtttgg ttatcaccag ttcgtgccat taaactagta gagcaccatc cgcgacactt 420gtcagcagat tatcctgata aaaaagagac ctttgagaag aatgcagctg cctatatcga 480aaaattgcaa gccttggata aggcttacgc agaaggtttg tctcaagcaa aacaaaagag 540ctttgtgact caacacgcag cctttaacta tcttgccttg gactatggga ctc 593108197PRTStreptococcus pneumoniae 108Ser Asn Gln Lys Gln Ala Asp Gly Lys Leu Asn Ile Val Thr Thr Phe1 5 10 15Tyr Pro Val Tyr Glu Phe Thr Lys Gln Val Ala Gly Asp Thr Ala Asn 20 25 30Val Glu Leu Leu Ile Gly Ala Gly Thr Glu Pro His Glu Tyr Glu Pro 35 40 45Ser Ala Lys Ala Val Ala Lys Ile Gln Asp Ala Asp Thr Phe Val Tyr 50 55 60Glu Asn Glu Asn Met Glu Thr Trp Val Pro Lys Leu Leu Asp Thr Leu65 70 75 80Asp Lys Lys Lys Val Lys Thr Ile Lys Ala Thr Gly Asp Met Leu Leu 85 90 95Leu Pro Gly Gly Glu Glu Glu Glu Gly Asp His Asp His Gly Glu Glu 100 105 110Gly His His His Glu Phe Asp Pro His Val Trp Leu Ser Pro Val Arg 115 120 125Ala Ile Lys Leu Val Glu His His Pro Arg His Leu Ser Ala Asp Tyr 130 135 140Pro Asp Lys Lys Glu Thr Phe Glu Lys Asn Ala Ala Ala Tyr Ile Glu145 150 155 160Lys Leu Gln Ala Leu Asp Lys Ala Tyr Ala Glu Gly Leu Ser Gln Ala 165 170 175Lys Gln Lys Ser Phe Val Thr Gln His Ala Ala Phe Asn Tyr Leu Ala 180 185 190Leu Asp Tyr Gly Thr 1951091003DNAStreptococcus pneumoniae 109tatcacagga tcgaacggta agacaaccac aacgactatg attggggaag ttttgactgc 60tgctggccaa catggtcttt tatcagggaa tatcggctat ccagctagtc aggttgctca 120aatagcatca gataaggaca cgcttgttat ggaactttct tctttccaac tcatgggtgt 180tcaagaattc catccagaga ttgcggttat taccaacctc atgccaactc atatcgacta 240ccatgggtca ttttcggaat atgtagcagc caagtggaat atccagaaca agatgacagc 300agctgatttc cttgtcttga actttaatca agacttggca aaagacttga cttccaagac 360agaagccact gttgtaccat tttcaacact tgaaaaggtt gatggagctt atctggaaga 420tggtcaactc tacttccgtg gtgaagtagt catggcagcg aatgaaatcg gtgttccagg 480tagccacaat gtggaaaatg cccttgcgac tattgctgta gccaagcttc gtgatgtgga 540caatcaaacc atcaaggaaa ctctttcagc cttcggtggt gtcaaacacc gtctccagtt 600tgtggatgac atcaagggtg ttaaattcta taacgacagt aaatcaacta atatcttggc 660tactcaaaaa gccttgtcag gatttgacaa cagcaaggtc gtcttgattg caggtggttt 720ggaccgtggc aatgagtttg acgaattggt gccagacatt actggactca agaagatggt 780catcctgggt caatctgcag aacgtgtcaa acgggcagca gacaaggctg gtgtcgctta 840tgtggaggcg acagatattg cagatgcgac ccgcaaggcc tatgagcttg cgactcaagg 900agatgtggtt cttcttagtc ctgccaatgc tagctgggat atgtatgcta actttgaagt 960acgtggcgac ctctttatcg acacagtagc ggagttaaaa gaa 1003110335PRTStreptococcus pneumoniae 110Gly Ile Thr Gly Ser Asn Gly Lys Thr Thr Thr Thr Thr Met Ile Gly1 5 10 15Glu Val Leu Thr Ala Ala Gly Gln His Gly Leu Leu Ser Gly Asn Ile 20 25 30Gly Tyr Pro Ala Ser Gln Val Ala Gln Ile Ala Ser Asp Lys Asp Thr 35 40 45Leu Val Met Glu Leu Ser Ser Phe Gln Leu Met Gly Val Gln Glu Phe 50 55 60His Pro Glu Ile Ala Val Ile Thr Asn Leu Met Pro Thr His Ile Asp65 70 75 80Tyr His Gly Ser Phe Ser Glu Tyr Val Ala Ala Lys Trp Asn Ile Gln 85 90 95Asn Lys Met Thr Ala Ala Asp Phe Leu Val Leu Asn Phe Asn Gln Asp 100 105 110Leu Ala Lys Asp Leu Thr Ser Lys Thr Glu Ala Thr Val Val Pro Phe 115 120 125Ser Thr Leu Glu Lys Val Asp Gly Ala Tyr Leu Glu Asp Gly Gln Leu 130 135 140Tyr Phe Arg Gly Glu Val Val Met Ala Ala Asn Glu Ile Gly Val Pro145 150 155 160Gly Ser His Asn Val Glu Asn Ala Leu Ala Thr Ile Ala Val Ala Lys 165 170 175Leu Arg Asp Val Asp Asn Gln Thr Ile Lys Glu Thr Leu Ser Ala Phe 180 185

190Gly Gly Val Lys His Arg Leu Gln Phe Val Asp Asp Ile Lys Gly Val 195 200 205Lys Phe Tyr Asn Asp Ser Lys Ser Thr Asn Ile Leu Ala Thr Gln Lys 210 215 220Ala Leu Ser Gly Phe Asp Asn Ser Lys Val Val Leu Ile Ala Gly Gly225 230 235 240Leu Asp Arg Gly Asn Glu Phe Asp Glu Leu Val Pro Asp Ile Thr Gly 245 250 255Leu Lys Lys Met Val Ile Leu Gly Gln Ser Ala Glu Arg Val Lys Arg 260 265 270Ala Ala Asp Lys Ala Gly Val Ala Tyr Val Glu Ala Thr Asp Ile Ala 275 280 285Asp Ala Thr Arg Lys Ala Tyr Glu Leu Ala Thr Gln Gly Asp Val Val 290 295 300Leu Leu Ser Pro Ala Asn Ala Ser Trp Asp Met Tyr Ala Asn Phe Glu305 310 315 320Val Arg Gly Asp Leu Phe Ile Asp Thr Val Ala Glu Leu Lys Glu 325 330 335111412DNAStreptococcus pneumoniae 111aagttcatcg aagatggttg ggaagtccac tatatcgggg acaagtgtgg tatcgaacac 60caagaaatcc ttaagtcagg tttggatgtc accttccatt ctattgcgac tggaaaattg 120cgtcgctatt tctcttggca aaatatgctg gacgtcttca aagttggttg gggaattgtc 180caatcgctct ttatcatgtt gcgactgcgt ccacagaccc ttttttcaaa ggggggcttt 240gtctcagtac cgcctgttat cgctgcgcgt gtgtcaggag tgcctgtctt tattcacgaa 300tctgacctgt ctatgggctt ggccaataaa atcgcctata aatttgcgac taagatgtat 360tcaacctttg aacaagcttc gagtttggct aaggttgagc atgtgggagc gg 412112137PRTStreptococcus pneumoniae 112Ser Ser Ser Lys Met Val Gly Lys Ser Thr Ile Ser Gly Thr Ser Val1 5 10 15Val Ser Asn Thr Lys Lys Ser Leu Ser Gln Val Trp Met Ser Pro Ser 20 25 30Ile Leu Leu Arg Leu Glu Asn Cys Val Ala Ile Ser Leu Gly Lys Ile 35 40 45Cys Trp Thr Ser Ser Lys Leu Val Gly Glu Leu Ser Asn Arg Ser Leu 50 55 60Ser Cys Cys Asp Cys Val His Arg Pro Phe Phe Gln Arg Gly Ala Leu65 70 75 80Ser Gln Tyr Arg Leu Leu Ser Leu Arg Val Cys Gln Glu Cys Leu Ser 85 90 95Leu Phe Thr Asn Leu Thr Cys Leu Trp Ala Trp Pro Ile Lys Ser Pro 100 105 110Ile Asn Leu Arg Leu Arg Cys Ile Gln Pro Leu Asn Lys Leu Arg Val 115 120 125Trp Leu Arg Leu Ser Met Trp Glu Arg 130 135113544DNAStreptococcus pneumoniae 113atcgctagct agtgaaatgc aagaaagtac acgtaaattc aaggttactg ctgacctaac 60agatgccggt gttggaacga ttgaagttcc tttgagcatt gaagatttac ccaatgggct 120gaccgctgtg gcgactccgc aaaaaattac agtcaagatt ggtaagaagg ctcagaagga 180taaggtaaag attgtaccag agattgaccc tagtcaaatt gatagtcggg tacaaattga 240aaatgtcatg gtgtcagata aagaagtgtc tattacgagt gaccaagaga cattggatag 300aattgataag attatcgctg ttttgccaac tagcgaacgt ataacaggta attacagtgg 360ttcagtacct ttgcaggcaa tcgaccgcaa tggtgttgtc ttaccggcag ttatcactcc 420gtttgataca ataatgaagg tgactacaaa accagtagca ccaagttcaa gcacatcaaa 480ttcaagtaca agcagttcat cggagacatc ttcgtcaacg aaagcaacta gttcaaaaac 540gaat 544114181PRTStreptococcus pneumoniae 114Ser Leu Ala Ser Glu Met Gln Glu Ser Thr Arg Lys Phe Lys Val Thr1 5 10 15Ala Asp Leu Thr Asp Ala Gly Val Gly Thr Ile Glu Val Pro Leu Ser 20 25 30Ile Glu Asp Leu Pro Asn Gly Leu Thr Ala Val Ala Thr Pro Gln Lys 35 40 45Ile Thr Val Lys Ile Gly Lys Lys Ala Gln Lys Asp Lys Val Lys Ile 50 55 60Val Pro Glu Ile Asp Pro Ser Gln Ile Asp Ser Arg Val Gln Ile Glu65 70 75 80Asn Val Met Val Ser Asp Lys Glu Val Ser Ile Thr Ser Asp Gln Glu 85 90 95Thr Leu Asp Arg Ile Asp Lys Ile Ile Ala Val Leu Pro Thr Ser Glu 100 105 110Arg Ile Thr Gly Asn Tyr Ser Gly Ser Val Pro Leu Gln Ala Ile Asp 115 120 125Arg Asn Gly Val Val Leu Pro Ala Val Ile Thr Pro Phe Asp Thr Ile 130 135 140Met Lys Val Thr Thr Lys Pro Val Ala Pro Ser Ser Ser Thr Ser Asn145 150 155 160Ser Ser Thr Ser Ser Ser Ser Glu Thr Ser Ser Ser Thr Lys Ala Thr 165 170 175Ser Ser Lys Thr Asn 1801151267DNAStreptococcus pneumoniae 115gcaccagatg gggcacaagg ttcagggatc agatgttgaa aagtactact ttacccaacg 60cggtcttgag caggcaggaa ttaccattct tccttttgat gaaaaaaatc tagacggtga 120tatggaaatt atcgctggaa atgcctttcg tccagataac aacgtcgaaa ttgcctatgc 180ggaccaaaat ggtatcagct acaaacgtta ccatgagttt ctaggtagct ttatgcgtga 240ctttgttagc atgggagtag caggagcaca tggaaaaact tcaacgacag gtatgttgtc 300tcatgtcttg tctcacatta cagataccag cttcttgatt ggagatggga caggtcgtgg 360ttcggccaat gccaaatatt ttgtctttga atctgacgaa tatgagcgtc acttcatgcc 420ttaccaccca gaatactcta ttatcaccaa cattgacttt gaccatccag attatttcac 480aagtctcgag gatgttttta atgcctttaa cgactatgcc aaacaaatca ccaagggtct 540ttttgtctat ggtgaagatg ctgaattgcg taagattacg tctgatgcac caatttatta 600ttatggtttt gaagctgaag gcaatgactt tgtagctagt gatcttcttc gttcaataac 660tggttcaacc ttcaccgttc atttccgtgg acaaaacttg gggcaattcc acattccaac 720ctttggtcgt cacaatatca tgaatgcgac agccgttatt ggtcttcttt acacagcagg 780atttgatttg aacttggtgc gtgagcactt gaaaacattt gccggtgtta aacgtcgttt 840cactgagaaa attgtcaatg atacagtgat tatcgatgac tttgcccacc atccaacaga 900aattattgcg accttggatg cggctcgtca gaaataccca agcaaggaaa ttgtagcagt 960ctttcaaccg cataccttta caagaaccat tgccttgttg gacgactttg cccatgcttt 1020aaaccaagca gatgctgttt atctagcgca aatttatggc tcggctcgtg aagtagatca 1080tggtgacgtt aaggtagaag acctagccaa caaaatcaac aaaaaacacc aagtgattac 1140tgttgaaaat gtttctccac tcctagacca tgacaatgct gtttacgtct ttatgggagc 1200aggagacatc caaacctatg aatactcatt tgagcgtctc ttgtctaact tgacaagcaa 1260tgttcaa 1267116422PRTStreptococcus pneumoniae 116His Gln Met Gly His Lys Val Gln Gly Ser Asp Val Glu Lys Tyr Tyr1 5 10 15Phe Thr Gln Arg Gly Leu Glu Gln Ala Gly Ile Thr Ile Leu Pro Phe 20 25 30Asp Glu Lys Asn Leu Asp Gly Asp Met Glu Ile Ile Ala Gly Asn Ala 35 40 45Phe Arg Pro Asp Asn Asn Val Glu Ile Ala Tyr Ala Asp Gln Asn Gly 50 55 60Ile Ser Tyr Lys Arg Tyr His Glu Phe Leu Gly Ser Phe Met Arg Asp65 70 75 80Phe Val Ser Met Gly Val Ala Gly Ala His Gly Lys Thr Ser Thr Thr 85 90 95Gly Met Leu Ser His Val Leu Ser His Ile Thr Asp Thr Ser Phe Leu 100 105 110Ile Gly Asp Gly Thr Gly Arg Gly Ser Ala Asn Ala Lys Tyr Phe Val 115 120 125Phe Glu Ser Asp Glu Tyr Glu Arg His Phe Met Pro Tyr His Pro Glu 130 135 140Tyr Ser Ile Ile Thr Asn Ile Asp Phe Asp His Pro Asp Tyr Phe Thr145 150 155 160Ser Leu Glu Asp Val Phe Asn Ala Phe Asn Asp Tyr Ala Lys Gln Ile 165 170 175Thr Lys Gly Leu Phe Val Tyr Gly Glu Asp Ala Glu Leu Arg Lys Ile 180 185 190Thr Ser Asp Ala Pro Ile Tyr Tyr Tyr Gly Phe Glu Ala Glu Gly Asn 195 200 205Asp Phe Val Ala Ser Asp Leu Leu Arg Ser Ile Thr Gly Ser Thr Phe 210 215 220Thr Val His Phe Arg Gly Gln Asn Leu Gly Gln Phe His Ile Pro Thr225 230 235 240Phe Gly Arg His Asn Ile Met Asn Ala Thr Ala Val Ile Gly Leu Leu 245 250 255Tyr Thr Ala Gly Phe Asp Leu Asn Leu Val Arg Glu His Leu Lys Thr 260 265 270Phe Ala Gly Val Lys Arg Arg Phe Thr Glu Lys Ile Val Asn Asp Thr 275 280 285Val Ile Ile Asp Asp Phe Ala His His Pro Thr Glu Ile Ile Ala Thr 290 295 300Leu Asp Ala Ala Arg Gln Lys Tyr Pro Ser Lys Glu Ile Val Ala Val305 310 315 320Phe Gln Pro His Thr Phe Thr Arg Thr Ile Ala Leu Leu Asp Asp Phe 325 330 335Ala His Ala Leu Asn Gln Ala Asp Ala Val Tyr Leu Ala Gln Ile Tyr 340 345 350Gly Ser Ala Arg Glu Val Asp His Gly Asp Val Lys Val Glu Asp Leu 355 360 365Ala Asn Lys Ile Asn Lys Lys His Gln Val Ile Thr Val Glu Asn Val 370 375 380Ser Pro Leu Leu Asp His Asp Asn Ala Val Tyr Val Phe Met Gly Ala385 390 395 400Gly Asp Ile Gln Thr Tyr Glu Tyr Ser Phe Glu Arg Leu Leu Ser Asn 405 410 415Leu Thr Ser Asn Val Gln 4201173121DNAStreptococcus pneumoniae 117ttttaaccca actgttggta ctttcctttt tactgcagga ttgagcttgt tagttttatt 60ggtttctaaa agggaaaatg gaaagaaacg acttgttcat tttctgctgt tgactagcat 120gggagttcaa ttgttgccgg ccagtgcttt tgggttgacc agccagattt tatctgccta 180taatagtcag ctttctatcg gagtcgggga acatttacca gagcctctga aaatcgaagg 240ttatcaatat attggttata tcaaaactaa gaaacaggat aatacagagc tttcaaggac 300agttgatggg aaatactctg ctcaaagaga tagtcaacca aactctacaa aaacatcaga 360tgtagttcat tcagctgatt tagaatggaa ccaaggacag gggaaggtta gtttacaagg 420tgaagcatca ggggatgatg gactttcaga aaaatcttct atagcagcag acaatctatc 480ttctaatgat tcattcgcaa gtcaagttga gcagaatccg gatcacaaag gagaatctgt 540agttcgacca acagtgccag aacaaggaaa tcctgtgtct gctacaacgg tgcagagtgc 600ggaagaggaa gtattggcga cgacaaatga tcgaccagag tataaacttc cattggaaac 660caaaggcacg caagaacccg gtcatgaggg tgaagccgca gtccgtgaag acttaccagt 720ctacactaag ccactagaaa ccaaaggtac acaaggaccc ggacatgaag gtgaagctgc 780agttcgcgag gaagaaccag cttacacaga accgttagca acgaaaggca cgcaagagcc 840aggtcatgag ggcaaagcta cagtccgcga agagactcta gagtacacgg aaccggtagc 900gacaaaaggc acacaagaac ccgaacatga gggcgaacgg scagtagaag aagaacttcc 960ggctttagag gtcactacac gaaatagaac ggaaatccag aatattcctt atacaacaga 1020agaaattcag gatccaacac ttctgaaaaa tcgtcgtaag attgaacgac aagggcaagc 1080agggacacgt acaattcaat atgaagacta catcgtaaat ggtaatgtcg tagaaactaa 1140agaagtgtca cgaactgaag tagctccggt caacgaagtc gttaaagtag gaacacttgt 1200gaaagttaaa cctacagtag aaattacaaa cttaacaaaa gttgagaaca aaaaatctat 1260aactgtaagt tataacttaa tagacactac ctcagcatat gtttctgcaa aaacgcaagt 1320tttccatgga gacaagctag ttaaagaggt ggatatagaa aatcctgcca aagagcaagt 1380aatatcaggt ttagattact acacaccgta tacagttaaa acacacctaa cttataattt 1440gggtgaaaat aatgaggaaa atactgaaac atcaactcaa gatttccaat tagagtataa 1500gaaaatagag attaaagata ttgattcagt agaattatac ggtaaagaaa atgatcgtta 1560tcgtagatat ttaagtctaa gtgaagcgcc gactgatacg gctaaatact ttgtaaaagt 1620gaaatcagat cgcttcaaag aaatgtacct acctgtaaaa tctattacag aaaatacgga 1680tggaacgtat aaagtgacgg tagccgttga tcaacttgtc gaagaaggta cagacggtta 1740caaagatgat tacacattta ctgtagctaa atctaaagca gagcaaccag gagtttacac 1800atcctttaaa cagctggtaa cagccatgca aagcaatctg tctggtgtct atacattggc 1860ttcagatatg accgcagatg aggtgagctt aggcgataag cagacaagtt atctcacagg 1920tgcatttaca gggagcttga tcggttctga tggaacaaaa tcgtatgcca tttatgattt 1980gaagaaacca ttatttgata cattaaatgg tgctacagtt agagatttgg atattaaaac 2040tgtttctgct gatagtaaag aaaatgtcgc agcgctggcg aaggcagcga atagcgcgaa 2100tattaataat gttgcagtag aaggaaaaat ctcaggtgcg aaatctgttg cgggattagt 2160agcgagcgca acaaatacag tgatagaaaa cagctcgttt acagggaaac ttatcgcaaa 2220tcaccaggac agtaataaaa atgatactgg aggaatagta ggtaatataa caggaaatag 2280ttcgagagtt aataaagtta gggtagatgc cttaatctct actaatgcac gcaataataa 2340ccaaacagct ggagggatag taggtagatt agaaaatggt gcattgatat ctaattcggt 2400tgctactgga gaaatacgaa atggtcaagg atattctaga gtcggaggaa tagtaggatc 2460tacgtggcaa aacggtcgag taaataatgt tgtgagtaac gtagatgttg gagatggtta 2520tgttatcacc ggtgatcaat acgcagcagc agatgtgaaa aatgcaagta catcagttga 2580taatagaaaa gcagacagat tcgctacaaa attatcaaaa gaccaaatag acgcgaaagt 2640tgctgattat ggaatcacag taactcttga tgatactggg caagatttaa aacgtaatct 2700aagagaagtt gattatacaa gactaaataa agcagaagct gaaagaaaag tagcttatag 2760caacatagaa aaactgatgc cattctacaa taaagaccta gtagttcact atggtaacaa 2820agtagcgaca acagataaac tttacactac agaattgtta gatgttgtgc cgatgaaaga 2880tgatgaagta gtaacggata ttaataataa gaaaaattca ataaataaag ttatgttaca 2940tttcaaagat aatacagtag aatacctaga tgtaacattc aaagaaaact tcataaacag 3000tcaagtaatc gaatacaatg ttacaggaaa agaatatata ttcacaccag aagcatttgt 3060ttcagactat acagcgataa cgaataacgt actaagcgac ttgcaaaatg taacacttaa 3120c 31211181040PRTStreptococcus pneumoniaeSITE(314)..(314)Xaa can be any naturally occurring amino acid 118Phe Asn Pro Thr Val Gly Thr Phe Leu Phe Thr Ala Gly Leu Ser Leu1 5 10 15Leu Val Leu Leu Val Ser Lys Arg Glu Asn Gly Lys Lys Arg Leu Val 20 25 30His Phe Leu Leu Leu Thr Ser Met Gly Val Gln Leu Leu Pro Ala Ser 35 40 45Ala Phe Gly Leu Thr Ser Gln Ile Leu Ser Ala Tyr Asn Ser Gln Leu 50 55 60Ser Ile Gly Val Gly Glu His Leu Pro Glu Pro Leu Lys Ile Glu Gly65 70 75 80Tyr Gln Tyr Ile Gly Tyr Ile Lys Thr Lys Lys Gln Asp Asn Thr Glu 85 90 95Leu Ser Arg Thr Val Asp Gly Lys Tyr Ser Ala Gln Arg Asp Ser Gln 100 105 110Pro Asn Ser Thr Lys Thr Ser Asp Val Val His Ser Ala Asp Leu Glu 115 120 125Trp Asn Gln Gly Gln Gly Lys Val Ser Leu Gln Gly Glu Ala Ser Gly 130 135 140Asp Asp Gly Leu Ser Glu Lys Ser Ser Ile Ala Ala Asp Asn Leu Ser145 150 155 160Ser Asn Asp Ser Phe Ala Ser Gln Val Glu Gln Asn Pro Asp His Lys 165 170 175Gly Glu Ser Val Val Arg Pro Thr Val Pro Glu Gln Gly Asn Pro Val 180 185 190Ser Ala Thr Thr Val Gln Ser Ala Glu Glu Glu Val Leu Ala Thr Thr 195 200 205Asn Asp Arg Pro Glu Tyr Lys Leu Pro Leu Glu Thr Lys Gly Thr Gln 210 215 220Glu Pro Gly His Glu Gly Glu Ala Ala Val Arg Glu Asp Leu Pro Val225 230 235 240Tyr Thr Lys Pro Leu Glu Thr Lys Gly Thr Gln Gly Pro Gly His Glu 245 250 255Gly Glu Ala Ala Val Arg Glu Glu Glu Pro Ala Tyr Thr Glu Pro Leu 260 265 270Ala Thr Lys Gly Thr Gln Glu Pro Gly His Glu Gly Lys Ala Thr Val 275 280 285Arg Glu Glu Thr Leu Glu Tyr Thr Glu Pro Val Ala Thr Lys Gly Thr 290 295 300Gln Glu Pro Glu His Glu Gly Glu Arg Xaa Val Glu Glu Glu Leu Pro305 310 315 320Ala Leu Glu Val Thr Thr Arg Asn Arg Thr Glu Ile Gln Asn Ile Pro 325 330 335Tyr Thr Thr Glu Glu Ile Gln Asp Pro Thr Leu Leu Lys Asn Arg Arg 340 345 350Lys Ile Glu Arg Gln Gly Gln Ala Gly Thr Arg Thr Ile Gln Tyr Glu 355 360 365Asp Tyr Ile Val Asn Gly Asn Val Val Glu Thr Lys Glu Val Ser Arg 370 375 380Thr Glu Val Ala Pro Val Asn Glu Val Val Lys Val Gly Thr Leu Val385 390 395 400Lys Val Lys Pro Thr Val Glu Ile Thr Asn Leu Thr Lys Val Glu Asn 405 410 415Lys Lys Ser Ile Thr Val Ser Tyr Asn Leu Ile Asp Thr Thr Ser Ala 420 425 430Tyr Val Ser Ala Lys Thr Gln Val Phe His Gly Asp Lys Leu Val Lys 435 440 445Glu Val Asp Ile Glu Asn Pro Ala Lys Glu Gln Val Ile Ser Gly Leu 450 455 460Asp Tyr Tyr Thr Pro Tyr Thr Val Lys Thr His Leu Thr Tyr Asn Leu465 470 475 480Gly Glu Asn Asn Glu Glu Asn Thr Glu Thr Ser Thr Gln Asp Phe Gln 485 490 495Leu Glu Tyr Lys Lys Ile Glu Ile Lys Asp Ile Asp Ser Val Glu Leu 500 505 510Tyr Gly Lys Glu Asn Asp Arg Tyr Arg Arg Tyr Leu Ser Leu Ser Glu 515 520 525Ala Pro Thr Asp Thr Ala Lys Tyr Phe Val Lys Val Lys Ser Asp Arg 530 535 540Phe Lys Glu Met Tyr Leu Pro Val Lys Ser Ile Thr Glu Asn Thr Asp545 550 555 560Gly Thr Tyr Lys Val Thr Val Ala Val Asp Gln Leu Val Glu Glu Gly 565 570 575Thr Asp Gly Tyr Lys Asp Asp Tyr Thr Phe Thr Val Ala Lys Ser Lys 580 585 590Ala Glu Gln Pro Gly Val Tyr Thr Ser Phe Lys Gln Leu Val Thr Ala 595 600 605Met Gln Ser Asn Leu Ser Gly Val Tyr Thr Leu Ala Ser Asp Met Thr 610 615 620Ala Asp Glu Val Ser Leu Gly Asp

Lys Gln Thr Ser Tyr Leu Thr Gly625 630 635 640Ala Phe Thr Gly Ser Leu Ile Gly Ser Asp Gly Thr Lys Ser Tyr Ala 645 650 655Ile Tyr Asp Leu Lys Lys Pro Leu Phe Asp Thr Leu Asn Gly Ala Thr 660 665 670Val Arg Asp Leu Asp Ile Lys Thr Val Ser Ala Asp Ser Lys Glu Asn 675 680 685Val Ala Ala Leu Ala Lys Ala Ala Asn Ser Ala Asn Ile Asn Asn Val 690 695 700Ala Val Glu Gly Lys Ile Ser Gly Ala Lys Ser Val Ala Gly Leu Val705 710 715 720Ala Ser Ala Thr Asn Thr Val Ile Glu Asn Ser Ser Phe Thr Gly Lys 725 730 735Leu Ile Ala Asn His Gln Asp Ser Asn Lys Asn Asp Thr Gly Gly Ile 740 745 750Val Gly Asn Ile Thr Gly Asn Ser Ser Arg Val Asn Lys Val Arg Val 755 760 765Asp Ala Leu Ile Ser Thr Asn Ala Arg Asn Asn Asn Gln Thr Ala Gly 770 775 780Gly Ile Val Gly Arg Leu Glu Asn Gly Ala Leu Ile Ser Asn Ser Val785 790 795 800Ala Thr Gly Glu Ile Arg Asn Gly Gln Gly Tyr Ser Arg Val Gly Gly 805 810 815Ile Val Gly Ser Thr Trp Gln Asn Gly Arg Val Asn Asn Val Val Ser 820 825 830Asn Val Asp Val Gly Asp Gly Tyr Val Ile Thr Gly Asp Gln Tyr Ala 835 840 845Ala Ala Asp Val Lys Asn Ala Ser Thr Ser Val Asp Asn Arg Lys Ala 850 855 860Asp Arg Phe Ala Thr Lys Leu Ser Lys Asp Gln Ile Asp Ala Lys Val865 870 875 880Ala Asp Tyr Gly Ile Thr Val Thr Leu Asp Asp Thr Gly Gln Asp Leu 885 890 895Lys Arg Asn Leu Arg Glu Val Asp Tyr Thr Arg Leu Asn Lys Ala Glu 900 905 910Ala Glu Arg Lys Val Ala Tyr Ser Asn Ile Glu Lys Leu Met Pro Phe 915 920 925Tyr Asn Lys Asp Leu Val Val His Tyr Gly Asn Lys Val Ala Thr Thr 930 935 940Asp Lys Leu Tyr Thr Thr Glu Leu Leu Asp Val Val Pro Met Lys Asp945 950 955 960Asp Glu Val Val Thr Asp Ile Asn Asn Lys Lys Asn Ser Ile Asn Lys 965 970 975Val Met Leu His Phe Lys Asp Asn Thr Val Glu Tyr Leu Asp Val Thr 980 985 990Phe Lys Glu Asn Phe Ile Asn Ser Gln Val Ile Glu Tyr Asn Val Thr 995 1000 1005Gly Lys Glu Tyr Ile Phe Thr Pro Glu Ala Phe Val Ser Asp Tyr 1010 1015 1020Thr Ala Ile Thr Asn Asn Val Leu Ser Asp Leu Gln Asn Val Thr 1025 1030 1035Leu Asn 10401191567DNAStreptococcus pneumoniae 119ttttaaccca actgttggta ctttcctttt tactgcagga ttgagcttgt tagttttatt 60ggtttctaaa agggaaaatg gaaagaaacg acttgttcat tttctgctgt tgactagcat 120gggagttcaa ttgttgccgg ccagtgcttt tgggttgacc agccagattt tatctgccta 180taatagtcag ctttctatcg gagtcgggga acatttacca gagcctctga aaatcgaagg 240ttatcaatat attggttata tcaaaactaa gaaacaggat aatacagagc tttcaaggac 300agttgatggg aaatactctg ctcaaagaga tagtcaacca aactctacaa aaacatcaga 360tgtagttcat tcagctgatt tagaatggaa ccaaggacag gggaaggtta gtttacaagg 420tgaagcatca ggggatgatg gactttcaga aaaatcttct atagcagcag acaatctatc 480ttctaatgat tcattcgcaa gtcaagttga gcagaatccg gatcacaaag gagaatctgt 540agttcgacca acagtgccag aacaaggaaa tcctgtgtct gctacaacgg tgcagagtgc 600ggaagaggaa gtattggcga cgacaaatga tcgaccagag tataaacttc cattggaaac 660caaaggcacg caagaacccg gtcatgaggg tgaagccgca gtccgtgaag acttaccagt 720ctacactaag ccactagaaa ccaaaggtac acaaggaccc ggacatgaag gtgaagctgc 780agttcgcgag gaagaaccag cttacacaga accgttagca acgaaaggca cgcaagagcc 840aggtcatgag ggcaaagcta cagtccgcga agagactcta gagtacacgg aaccggtagc 900gacaaaaggc acacaagaac ccgaacatga gggcgaacgg scagtagaag aagaacttcc 960ggctttagag gtcactacac gaaatagaac ggaaatccag aatattcctt atacaacaga 1020agaaattcag gatccaacac ttctgaaaaa tcgtcgtaag attgaacgac aagggcaagc 1080agggacacgt acaattcaat atgaagacta catcgtaaat ggtaatgtcg tagaaactaa 1140agaagtgtca cgaactgaag tagctccggt caacgaagtc gttaaagtag gaacacttgt 1200gaaagttaaa cctacagtag aaattacaaa cttaacaaaa gttgagaaca aaaaatctat 1260aactgtaagt tataacttaa tagacactac ctcagcatat gtttctgcaa aaacgcaagt 1320tttccatgga gacaagctag ttaaagaggt ggatatagaa aatcctgcca aagagcaagt 1380aatatcaggt ttagattact acacaccgta tacagttaaa acacacctaa cttataattt 1440gggtgaaaat aatgaggaaa atactgaaac atcaactcaa gatttccaat tagagtataa 1500gaaaatagag attaaagata ttgattcagt agaattatac ggtaaagaaa atgatcgtta 1560tcgtaga 1567120522PRTStreptococcus pneumoniaeSITE(314)..(314)Xaa can be any naturally occurring amino acid 120Phe Asn Pro Thr Val Gly Thr Phe Leu Phe Thr Ala Gly Leu Ser Leu1 5 10 15Leu Val Leu Leu Val Ser Lys Arg Glu Asn Gly Lys Lys Arg Leu Val 20 25 30His Phe Leu Leu Leu Thr Ser Met Gly Val Gln Leu Leu Pro Ala Ser 35 40 45Ala Phe Gly Leu Thr Ser Gln Ile Leu Ser Ala Tyr Asn Ser Gln Leu 50 55 60Ser Ile Gly Val Gly Glu His Leu Pro Glu Pro Leu Lys Ile Glu Gly65 70 75 80Tyr Gln Tyr Ile Gly Tyr Ile Lys Thr Lys Lys Gln Asp Asn Thr Glu 85 90 95Leu Ser Arg Thr Val Asp Gly Lys Tyr Ser Ala Gln Arg Asp Ser Gln 100 105 110Pro Asn Ser Thr Lys Thr Ser Asp Val Val His Ser Ala Asp Leu Glu 115 120 125Trp Asn Gln Gly Gln Gly Lys Val Ser Leu Gln Gly Glu Ala Ser Gly 130 135 140Asp Asp Gly Leu Ser Glu Lys Ser Ser Ile Ala Ala Asp Asn Leu Ser145 150 155 160Ser Asn Asp Ser Phe Ala Ser Gln Val Glu Gln Asn Pro Asp His Lys 165 170 175Gly Glu Ser Val Val Arg Pro Thr Val Pro Glu Gln Gly Asn Pro Val 180 185 190Ser Ala Thr Thr Val Gln Ser Ala Glu Glu Glu Val Leu Ala Thr Thr 195 200 205Asn Asp Arg Pro Glu Tyr Lys Leu Pro Leu Glu Thr Lys Gly Thr Gln 210 215 220Glu Pro Gly His Glu Gly Glu Ala Ala Val Arg Glu Asp Leu Pro Val225 230 235 240Tyr Thr Lys Pro Leu Glu Thr Lys Gly Thr Gln Gly Pro Gly His Glu 245 250 255Gly Glu Ala Ala Val Arg Glu Glu Glu Pro Ala Tyr Thr Glu Pro Leu 260 265 270Ala Thr Lys Gly Thr Gln Glu Pro Gly His Glu Gly Lys Ala Thr Val 275 280 285Arg Glu Glu Thr Leu Glu Tyr Thr Glu Pro Val Ala Thr Lys Gly Thr 290 295 300Gln Glu Pro Glu His Glu Gly Glu Arg Xaa Val Glu Glu Glu Leu Pro305 310 315 320Ala Leu Glu Val Thr Thr Arg Asn Arg Thr Glu Ile Gln Asn Ile Pro 325 330 335Tyr Thr Thr Glu Glu Ile Gln Asp Pro Thr Leu Leu Lys Asn Arg Arg 340 345 350Lys Ile Glu Arg Gln Gly Gln Ala Gly Thr Arg Thr Ile Gln Tyr Glu 355 360 365Asp Tyr Ile Val Asn Gly Asn Val Val Glu Thr Lys Glu Val Ser Arg 370 375 380Thr Glu Val Ala Pro Val Asn Glu Val Val Lys Val Gly Thr Leu Val385 390 395 400Lys Val Lys Pro Thr Val Glu Ile Thr Asn Leu Thr Lys Val Glu Asn 405 410 415Lys Lys Ser Ile Thr Val Ser Tyr Asn Leu Ile Asp Thr Thr Ser Ala 420 425 430Tyr Val Ser Ala Lys Thr Gln Val Phe His Gly Asp Lys Leu Val Lys 435 440 445Glu Val Asp Ile Glu Asn Pro Ala Lys Glu Gln Val Ile Ser Gly Leu 450 455 460Asp Tyr Tyr Thr Pro Tyr Thr Val Lys Thr His Leu Thr Tyr Asn Leu465 470 475 480Gly Glu Asn Asn Glu Glu Asn Thr Glu Thr Ser Thr Gln Asp Phe Gln 485 490 495Leu Glu Tyr Lys Lys Ile Glu Ile Lys Asp Ile Asp Ser Val Glu Leu 500 505 510Tyr Gly Lys Glu Asn Asp Arg Tyr Arg Arg 515 5201211561DNAStreptococcus pneumoniae 121tcgtagatat ttaagtctaa gtgaagcgcc gactgatacg gctaaatact ttgtaaaagt 60gaaatcagat cgcttcaaag aaatgtacct acctgtaaaa tctattacag aaaatacgga 120tggaacgtat aaagtgacgg tagccgttga tcaacttgtc gaagaaggta cagacggtta 180caaagatgat tacacattta ctgtagctaa atctaaagca gagcaaccag gagtttacac 240atcctttaaa cagctggtaa cagccatgca aagcaatctg tctggtgtct atacattggc 300ttcagatatg accgcagatg aggtgagctt aggcgataag cagacaagtt atctcacagg 360tgcatttaca gggagcttga tcggttctga tggaacaaaa tcgtatgcca tttatgattt 420gaagaaacca ttatttgata cattaaatgg tgctacagtt agagatttgg atattaaaac 480tgtttctgct gatagtaaag aaaatgtcgc agcgctggcg aaggcagcga atagcgcgaa 540tattaataat gttgcagtag aaggaaaaat ctcaggtgcg aaatctgttg cgggattagt 600agcgagcgca acaaatacag tgatagaaaa cagctcgttt acagggaaac ttatcgcaaa 660tcaccaggac agtaataaaa atgatactgg aggaatagta ggtaatataa caggaaatag 720ttcgagagtt aataaagtta gggtagatgc cttaatctct actaatgcac gcaataataa 780ccaaacagct ggagggatag taggtagatt agaaaatggt gcattgatat ctaattcggt 840tgctactgga gaaatacgaa atggtcaagg atattctaga gtcggaggaa tagtaggatc 900tacgtggcaa aacggtcgag taaataatgt tgtgagtaac gtagatgttg gagatggtta 960tgttatcacc ggtgatcaat acgcagcagc agatgtgaaa aatgcaagta catcagttga 1020taatagaaaa gcagacagat tcgctacaaa attatcaaaa gaccaaatag acgcgaaagt 1080tgctgattat ggaatcacag taactcttga tgatactggg caagatttaa aacgtaatct 1140aagagaagtt gattatacaa gactaaataa agcagaagct gaaagaaaag tagcttatag 1200caacatagaa aaactgatgc cattctacaa taaagaccta gtagttcact atggtaacaa 1260agtagcgaca acagataaac tttacactac agaattgtta gatgttgtgc cgatgaaaga 1320tgatgaagta gtaacggata ttaataataa gaaaaattca ataaataaag ttatgttaca 1380tttcaaagat aatacagtag aatacctaga tgtaacattc aaagaaaact tcataaacag 1440tcaagtaatc gaatacaatg ttacaggaaa agaatatata ttcacaccag aagcatttgt 1500ttcagactat acagcgataa cgaataacgt actaagcgac ttgcaaaatg taacacttaa 1560c 1561122520PRTStreptococcus pneumoniae 122Arg Arg Tyr Leu Ser Leu Ser Glu Ala Pro Thr Asp Thr Ala Lys Tyr1 5 10 15Phe Val Lys Val Lys Ser Asp Arg Phe Lys Glu Met Tyr Leu Pro Val 20 25 30Lys Ser Ile Thr Glu Asn Thr Asp Gly Thr Tyr Lys Val Thr Val Ala 35 40 45Val Asp Gln Leu Val Glu Glu Gly Thr Asp Gly Tyr Lys Asp Asp Tyr 50 55 60Thr Phe Thr Val Ala Lys Ser Lys Ala Glu Gln Pro Gly Val Tyr Thr65 70 75 80Ser Phe Lys Gln Leu Val Thr Ala Met Gln Ser Asn Leu Ser Gly Val 85 90 95Tyr Thr Leu Ala Ser Asp Met Thr Ala Asp Glu Val Ser Leu Gly Asp 100 105 110Lys Gln Thr Ser Tyr Leu Thr Gly Ala Phe Thr Gly Ser Leu Ile Gly 115 120 125Ser Asp Gly Thr Lys Ser Tyr Ala Ile Tyr Asp Leu Lys Lys Pro Leu 130 135 140Phe Asp Thr Leu Asn Gly Ala Thr Val Arg Asp Leu Asp Ile Lys Thr145 150 155 160Val Ser Ala Asp Ser Lys Glu Asn Val Ala Ala Leu Ala Lys Ala Ala 165 170 175Asn Ser Ala Asn Ile Asn Asn Val Ala Val Glu Gly Lys Ile Ser Gly 180 185 190Ala Lys Ser Val Ala Gly Leu Val Ala Ser Ala Thr Asn Thr Val Ile 195 200 205Glu Asn Ser Ser Phe Thr Gly Lys Leu Ile Ala Asn His Gln Asp Ser 210 215 220Asn Lys Asn Asp Thr Gly Gly Ile Val Gly Asn Ile Thr Gly Asn Ser225 230 235 240Ser Arg Val Asn Lys Val Arg Val Asp Ala Leu Ile Ser Thr Asn Ala 245 250 255Arg Asn Asn Asn Gln Thr Ala Gly Gly Ile Val Gly Arg Leu Glu Asn 260 265 270Gly Ala Leu Ile Ser Asn Ser Val Ala Thr Gly Glu Ile Arg Asn Gly 275 280 285Gln Gly Tyr Ser Arg Val Gly Gly Ile Val Gly Ser Thr Trp Gln Asn 290 295 300Gly Arg Val Asn Asn Val Val Ser Asn Val Asp Val Gly Asp Gly Tyr305 310 315 320Val Ile Thr Gly Asp Gln Tyr Ala Ala Ala Asp Val Lys Asn Ala Ser 325 330 335Thr Ser Val Asp Asn Arg Lys Ala Asp Arg Phe Ala Thr Lys Leu Ser 340 345 350Lys Asp Gln Ile Asp Ala Lys Val Ala Asp Tyr Gly Ile Thr Val Thr 355 360 365Leu Asp Asp Thr Gly Gln Asp Leu Lys Arg Asn Leu Arg Glu Val Asp 370 375 380Tyr Thr Arg Leu Asn Lys Ala Glu Ala Glu Arg Lys Val Ala Tyr Ser385 390 395 400Asn Ile Glu Lys Leu Met Pro Phe Tyr Asn Lys Asp Leu Val Val His 405 410 415Tyr Gly Asn Lys Val Ala Thr Thr Asp Lys Leu Tyr Thr Thr Glu Leu 420 425 430Leu Asp Val Val Pro Met Lys Asp Asp Glu Val Val Thr Asp Ile Asn 435 440 445Asn Lys Lys Asn Ser Ile Asn Lys Val Met Leu His Phe Lys Asp Asn 450 455 460Thr Val Glu Tyr Leu Asp Val Thr Phe Lys Glu Asn Phe Ile Asn Ser465 470 475 480Gln Val Ile Glu Tyr Asn Val Thr Gly Lys Glu Tyr Ile Phe Thr Pro 485 490 495Glu Ala Phe Val Ser Asp Tyr Thr Ala Ile Thr Asn Asn Val Leu Ser 500 505 510Asp Leu Gln Asn Val Thr Leu Asn 515 520123850DNAStreptococcus pneumoniae 123ctttggtttt gaaggaagta agcgtggaca atttgctgta gaaggaatca atcaacttcg 60tgagcatgta gacactctat tgattatctc aaacaacaat ttgcttgaaa ttgttgataa 120gaaaacaccg cttttggagg ctcttagcga agcggataac gttcttcgtc aaggtgttca 180agggattacc gatttgatta ccaatccagg attgattaac cttgactttg ccgatgtgaa 240aacggtaatg gcaaacaaag ggaatgctct tatgggtatt ggtatcggta gtggagaaga 300acgtgtggta gaagcggcac gtaaggcaat ctattcacca cttcttgaaa caactattga 360cggtgctgag gatgttatcg tcaacgttac tggtggtctt gacttaacct tgattgaggc 420agaagaggct tcacaaattg tgaaccaggc agcaggtcaa ggagtgaaca tctggctcgg 480tacttcaatt gatgaaagta tgcgtgatga aattcgtgta acagttgttg caacgggtgt 540tcgtcaagac cgcgtagaaa aggttgtggc tccacaagct agatctgcta ctaactaccg 600tgagacagtg aaaccagctc attcacatgg ctttgatcgt cattttgata tggcagaaac 660agttgaattg ccaaaacaaa atccacgtcg tttggaacca actcaggcat ctgcttttgg 720tgattgggat cttcgccgtg aatcgattgt tcgtacaaca gattcagtcg tttctccagt 780cgagcgcttt gaagccccaa tttcacaaga tgaagatgaa ttggatacac ctccattttt 840caaaaatcgt 850124283PRTStreptococcus pneumoniae 124Phe Gly Phe Glu Gly Ser Lys Arg Gly Gln Phe Ala Val Glu Gly Ile1 5 10 15Asn Gln Leu Arg Glu His Val Asp Thr Leu Leu Ile Ile Ser Asn Asn 20 25 30Asn Leu Leu Glu Ile Val Asp Lys Lys Thr Pro Leu Leu Glu Ala Leu 35 40 45Ser Glu Ala Asp Asn Val Leu Arg Gln Gly Val Gln Gly Ile Thr Asp 50 55 60Leu Ile Thr Asn Pro Gly Leu Ile Asn Leu Asp Phe Ala Asp Val Lys65 70 75 80Thr Val Met Ala Asn Lys Gly Asn Ala Leu Met Gly Ile Gly Ile Gly 85 90 95Ser Gly Glu Glu Arg Val Val Glu Ala Ala Arg Lys Ala Ile Tyr Ser 100 105 110Pro Leu Leu Glu Thr Thr Ile Asp Gly Ala Glu Asp Val Ile Val Asn 115 120 125Val Thr Gly Gly Leu Asp Leu Thr Leu Ile Glu Ala Glu Glu Ala Ser 130 135 140Gln Ile Val Asn Gln Ala Ala Gly Gln Gly Val Asn Ile Trp Leu Gly145 150 155 160Thr Ser Ile Asp Glu Ser Met Arg Asp Glu Ile Arg Val Thr Val Val 165 170 175Ala Thr Gly Val Arg Gln Asp Arg Val Glu Lys Val Val Ala Pro Gln 180 185 190Ala Arg Ser Ala Thr Asn Tyr Arg Glu Thr Val Lys Pro Ala His Ser 195 200 205His Gly Phe Asp Arg His Phe Asp Met Ala Glu Thr Val Glu Leu Pro 210 215 220Lys Gln Asn Pro Arg Arg Leu Glu Pro Thr Gln Ala Ser Ala Phe Gly225 230 235 240Asp Trp Asp Leu Arg Arg Glu Ser Ile Val Arg Thr Thr Asp Ser Val 245 250 255Val Ser Pro Val Glu Arg Phe Glu Ala Pro Ile Ser Gln Asp Glu Asp 260 265 270Glu Leu Asp Thr Pro Pro Phe Phe Lys Asn Arg 275 2801251051DNAStreptococcus pneumoniae 125ctactacctc tcgagagaaa gtgacctaga ggtgaccgtt tttgaccatg agcaaggtca

60agccaccaag gccgcagcag gaattatcag tccttggttt tccaaacgcc gtaataaagc 120ctggtacaag atggcgcgct tgggggctga tttttatgtg gatttattag ctgatttaga 180gaaatcagga caagaaatcg acttttacca gcgttcggga gtctttctct tgaaaaagga 240tgaatccaat ttggaagaac tttatcaact ggccctccag cgcagagaag aatctccctt 300gatagggcaa ttagccattc tgaaccaagc ctcagctaat gaattattcc ctggtttgca 360gggatttgac cgcctgctct atgcttctgg tggagcgaga gtagatggcc aacttttagt 420gactcgtttg ctggaagtca gtcatgtcaa gctggtcaaa gaaaaagtga ctctgacacc 480gttagcatca ggctaccaga ttggtgaaga ggagtttgag caggttattt tggcgacggg 540agcttggttg ggggacatgt tagagccttt aggttatgaa gtggatgtcc gtcctcaaaa 600aggacaacta cgagattatc agcttgccca agacatggaa gattaccctg ttgtcatgcc 660agaaggggag tgggatttga ttccctttgc aggtgggaaa ttatccttag gcgctaccca 720cgaaaatgac atgggatttg atttgacggt agatgaaacc ttgctccaac aaatggagga 780ggccaccttg actcactatc tgattttggc tgaagctact tcaaaatctg agcgtgttgg 840aatccgtgcc tacaccagtg atttctctcc tttctttggg caggtgcctg acttaactgg 900tgtctatgca gccagtggac taggttcatc aggcctcaca actggtccta tcattggtta 960ccatctagcc caactgatcc aagacaagga gttgaccttg gaccctctaa attacccaat 1020tgaaaactat gtcaaacgag taaaaagcga a 1051126350PRTStreptococcus pneumoniae 126Tyr Tyr Leu Ser Arg Glu Ser Asp Leu Glu Val Thr Val Phe Asp His1 5 10 15Glu Gln Gly Gln Ala Thr Lys Ala Ala Ala Gly Ile Ile Ser Pro Trp 20 25 30Phe Ser Lys Arg Arg Asn Lys Ala Trp Tyr Lys Met Ala Arg Leu Gly 35 40 45Ala Asp Phe Tyr Val Asp Leu Leu Ala Asp Leu Glu Lys Ser Gly Gln 50 55 60Glu Ile Asp Phe Tyr Gln Arg Ser Gly Val Phe Leu Leu Lys Lys Asp65 70 75 80Glu Ser Asn Leu Glu Glu Leu Tyr Gln Leu Ala Leu Gln Arg Arg Glu 85 90 95Glu Ser Pro Leu Ile Gly Gln Leu Ala Ile Leu Asn Gln Ala Ser Ala 100 105 110Asn Glu Leu Phe Pro Gly Leu Gln Gly Phe Asp Arg Leu Leu Tyr Ala 115 120 125Ser Gly Gly Ala Arg Val Asp Gly Gln Leu Leu Val Thr Arg Leu Leu 130 135 140Glu Val Ser His Val Lys Leu Val Lys Glu Lys Val Thr Leu Thr Pro145 150 155 160Leu Ala Ser Gly Tyr Gln Ile Gly Glu Glu Glu Phe Glu Gln Val Ile 165 170 175Leu Ala Thr Gly Ala Trp Leu Gly Asp Met Leu Glu Pro Leu Gly Tyr 180 185 190Glu Val Asp Val Arg Pro Gln Lys Gly Gln Leu Arg Asp Tyr Gln Leu 195 200 205Ala Gln Asp Met Glu Asp Tyr Pro Val Val Met Pro Glu Gly Glu Trp 210 215 220Asp Leu Ile Pro Phe Ala Gly Gly Lys Leu Ser Leu Gly Ala Thr His225 230 235 240Glu Asn Asp Met Gly Phe Asp Leu Thr Val Asp Glu Thr Leu Leu Gln 245 250 255Gln Met Glu Glu Ala Thr Leu Thr His Tyr Leu Ile Leu Ala Glu Ala 260 265 270Thr Ser Lys Ser Glu Arg Val Gly Ile Arg Ala Tyr Thr Ser Asp Phe 275 280 285Ser Pro Phe Phe Gly Gln Val Pro Asp Leu Thr Gly Val Tyr Ala Ala 290 295 300Ser Gly Leu Gly Ser Ser Gly Leu Thr Thr Gly Pro Ile Ile Gly Tyr305 310 315 320His Leu Ala Gln Leu Ile Gln Asp Lys Glu Leu Thr Leu Asp Pro Leu 325 330 335Asn Tyr Pro Ile Glu Asn Tyr Val Lys Arg Val Lys Ser Glu 340 345 350127352DNAStreptococcus pneumoniae 127taaggtcaaa agtcagaccg ctaagaaagt gctagaaaag attggagctg actcggttat 60ctcgccagag tatgaaatgg ggcagtctct agcacagacc attcttttcc ataatagtgt 120tgatgtcttt cagttggata aaaatgtgtc tatcgtggag atgaaaattc ctcagtcttg 180ggcaggtcaa agtctgagta aattagacct ccgtggcaaa tacaatctga atattttggg 240tttccgagag caggaaaatt ccccattgga tgttgaattt ggaccagatg acctcttgaa 300agcagatacc tatattttgg cagtcatcaa caaccagtat ttggataccc ta 352128117PRTStreptococcus pneumoniae 128Lys Val Lys Ser Gln Thr Ala Lys Lys Val Leu Glu Lys Ile Gly Ala1 5 10 15Asp Ser Val Ile Ser Pro Glu Tyr Glu Met Gly Gln Ser Leu Ala Gln 20 25 30Thr Ile Leu Phe His Asn Ser Val Asp Val Phe Gln Leu Asp Lys Asn 35 40 45Val Ser Ile Val Glu Met Lys Ile Pro Gln Ser Trp Ala Gly Gln Ser 50 55 60Leu Ser Lys Leu Asp Leu Arg Gly Lys Tyr Asn Leu Asn Ile Leu Gly65 70 75 80Phe Arg Glu Gln Glu Asn Ser Pro Leu Asp Val Glu Phe Gly Pro Asp 85 90 95Asp Leu Leu Lys Ala Asp Thr Tyr Ile Leu Ala Val Ile Asn Asn Gln 100 105 110Tyr Leu Asp Thr Leu 115129247DNAStreptococcus pneumoniae 129tgacgggtct caggatcaga ctcaggaaat cgctgagtgt ttagctagca agtatcctaa 60tatcgttaga gccatctatc aggaaaataa atgccatggc ggtgcggtca atcgtggctt 120ggtagaggct tctgggcgct attttaaagt agttgacagt gatgactggg tggatcctcg 180tgcctacttg aaaattcttg aaacttgcag gaacttgaga gcaaaggtca agaggtggat 240gtctttg 24713082PRTStreptococcus pneumoniae 130Asp Gly Ser Gln Asp Gln Thr Gln Glu Ile Ala Glu Cys Leu Ala Ser1 5 10 15Lys Tyr Pro Asn Ile Val Arg Ala Ile Tyr Gln Glu Asn Lys Cys His 20 25 30Gly Gly Ala Val Asn Arg Gly Leu Val Glu Ala Ser Gly Arg Tyr Phe 35 40 45Lys Val Val Asp Ser Asp Asp Trp Val Asp Pro Arg Ala Tyr Leu Lys 50 55 60Ile Leu Glu Thr Cys Arg Asn Leu Arg Ala Lys Val Lys Arg Trp Met65 70 75 80Ser Leu1311744DNAStreptococcus pneumoniae 131tagaggcttt gccaaatggt gggaagggca cgagcgtcga aaagaggaac gctttgtcaa 60acaagaagaa aaagctcgcc aaaaggctga gaaagaggct agattagaac aagaagagac 120tgaaaaagcc ttactcgatt tgcctcctgt tgatatggaa acgggtgaaa ttctgacaga 180ggaagctgtt caaaatcttc cacctattcc agaagaaaag tgggtggaac cagaaatcat 240cctgcctcaa gctgaactta aattccctga acaggaagat gactcagatg acgaagatgt 300tcaggtcgat ttttcagcca aagaagccct tgaatacaaa cttccaagct tacaactctt 360tgcaccagat aaaccaaaag atcagtctaa agagaagaaa attgtcagag aaaatatcaa 420aatcttagaa gcaacctttg ctagctttgg tattaaggta acagttgaac gggccgaaat 480tgggccatca gtgaccaagt atgaagtcaa gccggctgtt ggtgtaaggg tcaaccgcat 540ttccaatcta tcagatgacc tcgctctagc cttggctgcc aaagatgtcc ggattgaagc 600accaatccct gggaaatccc taatcggaat tgaagtgccc aactccgata ttgccactgt 660atctttccga gaactatggg aacaatcgca aacgaaagca gaaaatttct tggaaattcc 720tttagggaag gctgttaatg gaaccgcaag agcttttgac ctttctaaaa tgccccactt 780gctagttgca ggttcaacgg gttcagggaa gtcagtagca gttaacggca ttattgctag 840cattctcatg aaggcgagac cagatcaagt taaatttatg atggtcgatc ccaagatggt 900tgagttatct gtttacaatg atattcccca cctcttgatt ccagtcgtga ccaatccacg 960caaagccagc aaggctctgc aaaaggttgt ggatgaaatg gaaaaccgtt atgaactctt 1020tgccaaggtg ggagttcgga atattgcagg ttttaatgcc aaggtagaag agttcaattc 1080ccagtctgag tacaagcaaa ttccgctacc attcattgtc gtgattgtgg atgagttggc 1140tgacctcatg atggtggcca gcaaggaagt ggaagatgct atcatccgtc ttgggcagaa 1200ggcgcgtgct gcaggtatcc acatgattct tgcaactcag cgtccatctg ttgatgtcat 1260ctctggtttg attaaggcca atgttccatc tcgtgtagca tttgcggttt catcaggaac 1320agactcccgt acgattttgg atgaaaatgg agcagaaaaa cttcttggtc gaggagacat 1380gctctttaaa ccgattgatg aaaatcatcc agttcgtctc caaggctcct ttatctcgga 1440tgacgatgtt gagcgcattg tgaacttcat caagactcag gcagatgcag actacgatga 1500gagttttgat ccaggtgagg tttctgaaaa tgaaggagaa ttttcggatg gagatgctgg 1560tggtgatccg ctttttgaag aagctaagtc tttggttatc gaaacacaga aagccagtgc 1620gtctatgatt cagcgtcgtt tatcagttgg atttaaccgt gcgacccgtc tcatggaaga 1680actggagata gcaggtgtca tcggtccagc tgaaggtacc aaacctcgaa aagtgttaca 1740acaa 1744132581PRTStreptococcus pneumoniae 132Arg Gly Phe Ala Lys Trp Trp Glu Gly His Glu Arg Arg Lys Glu Glu1 5 10 15Arg Phe Val Lys Gln Glu Glu Lys Ala Arg Gln Lys Ala Glu Lys Glu 20 25 30Ala Arg Leu Glu Gln Glu Glu Thr Glu Lys Ala Leu Leu Asp Leu Pro 35 40 45Pro Val Asp Met Glu Thr Gly Glu Ile Leu Thr Glu Glu Ala Val Gln 50 55 60Asn Leu Pro Pro Ile Pro Glu Glu Lys Trp Val Glu Pro Glu Ile Ile65 70 75 80Leu Pro Gln Ala Glu Leu Lys Phe Pro Glu Gln Glu Asp Asp Ser Asp 85 90 95Asp Glu Asp Val Gln Val Asp Phe Ser Ala Lys Glu Ala Leu Glu Tyr 100 105 110Lys Leu Pro Ser Leu Gln Leu Phe Ala Pro Asp Lys Pro Lys Asp Gln 115 120 125Ser Lys Glu Lys Lys Ile Val Arg Glu Asn Ile Lys Ile Leu Glu Ala 130 135 140Thr Phe Ala Ser Phe Gly Ile Lys Val Thr Val Glu Arg Ala Glu Ile145 150 155 160Gly Pro Ser Val Thr Lys Tyr Glu Val Lys Pro Ala Val Gly Val Arg 165 170 175Val Asn Arg Ile Ser Asn Leu Ser Asp Asp Leu Ala Leu Ala Leu Ala 180 185 190Ala Lys Asp Val Arg Ile Glu Ala Pro Ile Pro Gly Lys Ser Leu Ile 195 200 205Gly Ile Glu Val Pro Asn Ser Asp Ile Ala Thr Val Ser Phe Arg Glu 210 215 220Leu Trp Glu Gln Ser Gln Thr Lys Ala Glu Asn Phe Leu Glu Ile Pro225 230 235 240Leu Gly Lys Ala Val Asn Gly Thr Ala Arg Ala Phe Asp Leu Ser Lys 245 250 255Met Pro His Leu Leu Val Ala Gly Ser Thr Gly Ser Gly Lys Ser Val 260 265 270Ala Val Asn Gly Ile Ile Ala Ser Ile Leu Met Lys Ala Arg Pro Asp 275 280 285Gln Val Lys Phe Met Met Val Asp Pro Lys Met Val Glu Leu Ser Val 290 295 300Tyr Asn Asp Ile Pro His Leu Leu Ile Pro Val Val Thr Asn Pro Arg305 310 315 320Lys Ala Ser Lys Ala Leu Gln Lys Val Val Asp Glu Met Glu Asn Arg 325 330 335Tyr Glu Leu Phe Ala Lys Val Gly Val Arg Asn Ile Ala Gly Phe Asn 340 345 350Ala Lys Val Glu Glu Phe Asn Ser Gln Ser Glu Tyr Lys Gln Ile Pro 355 360 365Leu Pro Phe Ile Val Val Ile Val Asp Glu Leu Ala Asp Leu Met Met 370 375 380Val Ala Ser Lys Glu Val Glu Asp Ala Ile Ile Arg Leu Gly Gln Lys385 390 395 400Ala Arg Ala Ala Gly Ile His Met Ile Leu Ala Thr Gln Arg Pro Ser 405 410 415Val Asp Val Ile Ser Gly Leu Ile Lys Ala Asn Val Pro Ser Arg Val 420 425 430Ala Phe Ala Val Ser Ser Gly Thr Asp Ser Arg Thr Ile Leu Asp Glu 435 440 445Asn Gly Ala Glu Lys Leu Leu Gly Arg Gly Asp Met Leu Phe Lys Pro 450 455 460Ile Asp Glu Asn His Pro Val Arg Leu Gln Gly Ser Phe Ile Ser Asp465 470 475 480Asp Asp Val Glu Arg Ile Val Asn Phe Ile Lys Thr Gln Ala Asp Ala 485 490 495Asp Tyr Asp Glu Ser Phe Asp Pro Gly Glu Val Ser Glu Asn Glu Gly 500 505 510Glu Phe Ser Asp Gly Asp Ala Gly Gly Asp Pro Leu Phe Glu Glu Ala 515 520 525Lys Ser Leu Val Ile Glu Thr Gln Lys Ala Ser Ala Ser Met Ile Gln 530 535 540Arg Arg Leu Ser Val Gly Phe Asn Arg Ala Thr Arg Leu Met Glu Glu545 550 555 560Leu Glu Ile Ala Gly Val Ile Gly Pro Ala Glu Gly Thr Lys Pro Arg 565 570 575Lys Val Leu Gln Gln 580133829DNAStreptococcus pneumoniae 133tcaaaaagag aaggaaaact tggttattgc tgggaaaata ggtccagaac cagaaatttt 60ggccaatatg tataagttgc tgattgaaga aaataccagc atgactgcga ctgttaaacc 120gaattttggg aagacaagct tcctttatga agctctgaaa aaaggcgata ttgacatcta 180tcctgaattt actggtacgg tgactgaaag tttgcttcaa ccatcaccca aggtgagtca 240tgaaccagaa caggtttatc aggtggcgcg tgatggcatt gctaagcagg atcatctagc 300ctatctcaaa cccatgtctt atcaaaacac ctatgctgta gctgttccga aaaagattgc 360tcaagaatat ggcttgaaga ccatttcaga cttgaaaaaa gtggaagggc agttgaaggc 420aggttttaca ctcgagttta acgaccgtga agatggaaat aagggcttgc aatcaatgta 480tggtctcaat ctcaatgtag cgaccattga gccagccctt cgctatcagg ctattcagtc 540aggggatatt caaatcacgg atgcctattc gactgatgcg gaattggagc gttatgattt 600acaggtcttg gaagatgaca agcaactctt cccaccttat caaggggctc cactcatgaa 660agaagctctt ctcaagaaac acccagagtt ggaaagagtt cttaatacat tggctggtaa 720gattacagaa agccagatga gccagctcaa ctaccaagtc ggtgttgaag gcaagtcagc 780aaagcaagta gccaaggagt ttctccaaga acaaggtttg ttgaagaaa 829134276PRTStreptococcus pneumoniae 134Gln Lys Glu Lys Glu Asn Leu Val Ile Ala Gly Lys Ile Gly Pro Glu1 5 10 15Pro Glu Ile Leu Ala Asn Met Tyr Lys Leu Leu Ile Glu Glu Asn Thr 20 25 30Ser Met Thr Ala Thr Val Lys Pro Asn Phe Gly Lys Thr Ser Phe Leu 35 40 45Tyr Glu Ala Leu Lys Lys Gly Asp Ile Asp Ile Tyr Pro Glu Phe Thr 50 55 60Gly Thr Val Thr Glu Ser Leu Leu Gln Pro Ser Pro Lys Val Ser His65 70 75 80Glu Pro Glu Gln Val Tyr Gln Val Ala Arg Asp Gly Ile Ala Lys Gln 85 90 95Asp His Leu Ala Tyr Leu Lys Pro Met Ser Tyr Gln Asn Thr Tyr Ala 100 105 110Val Ala Val Pro Lys Lys Ile Ala Gln Glu Tyr Gly Leu Lys Thr Ile 115 120 125Ser Asp Leu Lys Lys Val Glu Gly Gln Leu Lys Ala Gly Phe Thr Leu 130 135 140Glu Phe Asn Asp Arg Glu Asp Gly Asn Lys Gly Leu Gln Ser Met Tyr145 150 155 160Gly Leu Asn Leu Asn Val Ala Thr Ile Glu Pro Ala Leu Arg Tyr Gln 165 170 175Ala Ile Gln Ser Gly Asp Ile Gln Ile Thr Asp Ala Tyr Ser Thr Asp 180 185 190Ala Glu Leu Glu Arg Tyr Asp Leu Gln Val Leu Glu Asp Asp Lys Gln 195 200 205Leu Phe Pro Pro Tyr Gln Gly Ala Pro Leu Met Lys Glu Ala Leu Leu 210 215 220Lys Lys His Pro Glu Leu Glu Arg Val Leu Asn Thr Leu Ala Gly Lys225 230 235 240Ile Thr Glu Ser Gln Met Ser Gln Leu Asn Tyr Gln Val Gly Val Glu 245 250 255Gly Lys Ser Ala Lys Gln Val Ala Lys Glu Phe Leu Gln Glu Gln Gly 260 265 270Leu Leu Lys Lys 275135712DNAStreptococcus pneumoniae 135acgttctatt gaggaccact ttgattcaaa cttcgaattg gaatataacc tcaaagaaaa 60agggaaaaca gatcttttga agctagttga taaaacaact gacatgcgtc tgcattttat 120ccgccaaact catccacgcg gtctcggaga tgctgttttg caagccaagg ctttcgtcgg 180aaatgaacct tttgtcgtta tgcttggtga tgacttgatg gatatcacag acgaaaaggc 240tgttccactt accaaacaac tcatggatga ctacgagcgt acccacgcgt ctactatcgc 300tgtcatgcca gtccctcatg acgaagtatc tgcttacggg gttattgctc cgcaaggcga 360aggaaaagat ggtctttaca gtgttgaaac ctttgttgaa aaaccagctc cagaggacgc 420tcctagcgac cttgctatta tcggacgcta cctcctcacg cctgaaattt ttgagattct 480cgaaaagcaa gctccaggtg caggaaatga aattcagctg acagatgcaa tcgacaccct 540caataaaaca caacgtgtat ttgctcgtga gttcaaaggg gctcgttacg atgtcggaga 600caagtttggc ttcatgaaaa catccatcga ctacgccctc aaacacccac aagtcaaaga 660tgatttgaag aattacctca tccaacttgg aaaagaattg actgagaagg aa 712136237PRTStreptococcus pneumoniae 136Arg Ser Ile Glu Asp His Phe Asp Ser Asn Phe Glu Leu Glu Tyr Asn1 5 10 15Leu Lys Glu Lys Gly Lys Thr Asp Leu Leu Lys Leu Val Asp Lys Thr 20 25 30Thr Asp Met Arg Leu His Phe Ile Arg Gln Thr His Pro Arg Gly Leu 35 40 45Gly Asp Ala Val Leu Gln Ala Lys Ala Phe Val Gly Asn Glu Pro Phe 50 55 60Val Val Met Leu Gly Asp Asp Leu Met Asp Ile Thr Asp Glu Lys Ala65 70 75 80Val Pro Leu Thr Lys Gln Leu Met Asp Asp Tyr Glu Arg Thr His Ala 85 90 95Ser Thr Ile Ala Val Met Pro Val Pro His Asp Glu Val Ser Ala Tyr 100 105 110Gly Val Ile Ala Pro Gln Gly Glu Gly Lys Asp Gly Leu Tyr Ser Val 115 120 125Glu Thr Phe Val Glu Lys Pro Ala Pro Glu Asp Ala Pro Ser Asp Leu 130 135 140Ala Ile Ile Gly Arg Tyr Leu Leu Thr Pro Glu Ile Phe Glu Ile Leu145 150 155 160Glu Lys Gln Ala Pro Gly Ala Gly Asn Glu Ile Gln Leu Thr Asp Ala 165 170 175Ile Asp Thr Leu Asn Lys Thr Gln Arg Val Phe Ala Arg Glu Phe Lys 180

185 190Gly Ala Arg Tyr Asp Val Gly Asp Lys Phe Gly Phe Met Lys Thr Ser 195 200 205Ile Asp Tyr Ala Leu Lys His Pro Gln Val Lys Asp Asp Leu Lys Asn 210 215 220Tyr Leu Ile Gln Leu Gly Lys Glu Leu Thr Glu Lys Glu225 230 235137502DNAStreptococcus pneumoniae 137cgctcaaaat accagaggtg ttcagctaat cgagcacgtt tctcctcaaa tgttgaaagc 60ccaattggag agtgtctttt ctgatattcc acctcaggct gtaaaaactg gaatgttggc 120tactactgaa atcatggaaa tcatccaacc ctatcttaaa aaactggatt gtccctatgt 180ccttgatcct gttatggttg ctacaagtgg agatgccttg attgactcaa atgctagaga 240ctatctcaaa acaaacttac tacctctagc aactattatt acgccaaatc ttcctgaagc 300agaagagatt gttggttttt caatccatga ccccgaagac atgcagcgtg ctggtcgcct 360gattttaaaa gaatttggtc ctcagtctgt ggttatcaaa ggcggacatc tcaaaggtgg 420tgctaaagat ttcctcttta ccaagaatga acaatttgtc tgggaaagcc cacgaattca 480aacctgtcac acccatggta ct 502138167PRTStreptococcus pneumoniae 138Ala Gln Asn Thr Arg Gly Val Gln Leu Ile Glu His Val Ser Pro Gln1 5 10 15Met Leu Lys Ala Gln Leu Glu Ser Val Phe Ser Asp Ile Pro Pro Gln 20 25 30Ala Val Lys Thr Gly Met Leu Ala Thr Thr Glu Ile Met Glu Ile Ile 35 40 45Gln Pro Tyr Leu Lys Lys Leu Asp Cys Pro Tyr Val Leu Asp Pro Val 50 55 60Met Val Ala Thr Ser Gly Asp Ala Leu Ile Asp Ser Asn Ala Arg Asp65 70 75 80Tyr Leu Lys Thr Asn Leu Leu Pro Leu Ala Thr Ile Ile Thr Pro Asn 85 90 95Leu Pro Glu Ala Glu Glu Ile Val Gly Phe Ser Ile His Asp Pro Glu 100 105 110Asp Met Gln Arg Ala Gly Arg Leu Ile Leu Lys Glu Phe Gly Pro Gln 115 120 125Ser Val Val Ile Lys Gly Gly His Leu Lys Gly Gly Ala Lys Asp Phe 130 135 140Leu Phe Thr Lys Asn Glu Gln Phe Val Trp Glu Ser Pro Arg Ile Gln145 150 155 160Thr Cys His Thr His Gly Thr 165139805DNAStreptococcus pneumoniae 139aattgtacaa ttagaaaaag atagcaaatc agacaaagaa caagttgata aactatttga 60atcatttgat gcatcttcag atgaatctat ttctaaatta aaagaactat ctgaaacttc 120acttaaaacc gatgcaggta aagactatct taataacaaa gtcaaagaat catctaaagc 180aattgtagat tttcatttgc aaaaaggttt ggcttatgat gttaaagatt cagatgacaa 240atttaaagat aaagcaactc ttgaaacaaa tgtaaaagaa attacaaaac aaattgattt 300tatcaaaaaa gttgatgaaa cttttaaaca agagaatttg gaagaaactc ttaaatctct 360aaatgatctt gttgataaat atcaaaaaca aatcgaactt ttgaagaaag aagaagaaaa 420agctgctgaa aaagctgctg aaaaagcaaa ggaatcttct agtcaaagta attcttctgg 480tagtgcttct aatgagtctt ataatggatc ttccaattca aatgtagatt atagttcatc 540tgaacaaact aatggatatt caaataatta tggcggtcaa gattattctg gttcaggaga 600tagttcaaca aatggtggat catcagaaca atattcatct agcaattcaa acagcggagc 660aaataatgtc tacagatata aaggcactgg tgctgacggc tatcaaagat actactacaa 720agatcataat aatggagatg tgtatgatga cgatggaaat taccttggga actttggtgg 780cggcattgca gaacctagtc aacgc 805140268PRTStreptococcus pneumoniae 140Ile Val Gln Leu Glu Lys Asp Ser Lys Ser Asp Lys Glu Gln Val Asp1 5 10 15Lys Leu Phe Glu Ser Phe Asp Ala Ser Ser Asp Glu Ser Ile Ser Lys 20 25 30Leu Lys Glu Leu Ser Glu Thr Ser Leu Lys Thr Asp Ala Gly Lys Asp 35 40 45Tyr Leu Asn Asn Lys Val Lys Glu Ser Ser Lys Ala Ile Val Asp Phe 50 55 60His Leu Gln Lys Gly Leu Ala Tyr Asp Val Lys Asp Ser Asp Asp Lys65 70 75 80Phe Lys Asp Lys Ala Thr Leu Glu Thr Asn Val Lys Glu Ile Thr Lys 85 90 95Gln Ile Asp Phe Ile Lys Lys Val Asp Glu Thr Phe Lys Gln Glu Asn 100 105 110Leu Glu Glu Thr Leu Lys Ser Leu Asn Asp Leu Val Asp Lys Tyr Gln 115 120 125Lys Gln Ile Glu Leu Leu Lys Lys Glu Glu Glu Lys Ala Ala Glu Lys 130 135 140Ala Ala Glu Lys Ala Lys Glu Ser Ser Ser Gln Ser Asn Ser Ser Gly145 150 155 160Ser Ala Ser Asn Glu Ser Tyr Asn Gly Ser Ser Asn Ser Asn Val Asp 165 170 175Tyr Ser Ser Ser Glu Gln Thr Asn Gly Tyr Ser Asn Asn Tyr Gly Gly 180 185 190Gln Asp Tyr Ser Gly Ser Gly Asp Ser Ser Thr Asn Gly Gly Ser Ser 195 200 205Glu Gln Tyr Ser Ser Ser Asn Ser Asn Ser Gly Ala Asn Asn Val Tyr 210 215 220Arg Tyr Lys Gly Thr Gly Ala Asp Gly Tyr Gln Arg Tyr Tyr Tyr Lys225 230 235 240Asp His Asn Asn Gly Asp Val Tyr Asp Asp Asp Gly Asn Tyr Leu Gly 245 250 255Asn Phe Gly Gly Gly Ile Ala Glu Pro Ser Gln Arg 260 265141211DNAStreptococcus pneumoniae 141tctgaccaag caaaaagaag cagtcaatga caaaggaaaa gcagctgttg ttaaggtggt 60ggaaagccag gcagaacttt atagcttaga aaagaatgaa gatgctagcc taagaaagtt 120acaagcagat ggacgcatca cggaagaaca ggctaaagct tataaagaat acaatgataa 180aaatggagga gcaaatcgta aagtcaatga t 21114270PRTStreptococcus pneumoniae 142Leu Thr Lys Gln Lys Glu Ala Val Asn Asp Lys Gly Lys Ala Ala Val1 5 10 15Val Lys Val Val Glu Ser Gln Ala Glu Leu Tyr Ser Leu Glu Lys Asn 20 25 30Glu Asp Ala Ser Leu Arg Lys Leu Gln Ala Asp Gly Arg Ile Thr Glu 35 40 45Glu Gln Ala Lys Ala Tyr Lys Glu Tyr Asn Asp Lys Asn Gly Gly Ala 50 55 60Asn Arg Lys Val Asn Asp65 70143331DNAStreptococcus pneumoniae 143gtccggctct gtccagtcca ctttttcagc ggtagaggaa cagattttct ttatggagtt 60tgaagaactc tatcgggaaa cccaaaaacg cagtgtagcc agtcagcaaa agactagtct 120gaacttagat gggcagacgc ttagcaatgg cagtcaaaag ttgccagtcc ctaaaggaat 180tcaggcccca tcaggccaaa gtattacatt tgaccgagct gggggcaatt cgtccctggc 240taaggttgaa tttcagacca gtaaaggagc gattcgctat caattatatc taggaaatgg 300aaaaattaaa cgcattaagg aaacaaaaaa t 331144110PRTStreptococcus pneumoniae 144Ser Gly Ser Val Gln Ser Thr Phe Ser Ala Val Glu Glu Gln Ile Phe1 5 10 15Phe Met Glu Phe Glu Glu Leu Tyr Arg Glu Thr Gln Lys Arg Ser Val 20 25 30Ala Ser Gln Gln Lys Thr Ser Leu Asn Leu Asp Gly Gln Thr Leu Ser 35 40 45Asn Gly Ser Gln Lys Leu Pro Val Pro Lys Gly Ile Gln Ala Pro Ser 50 55 60Gly Gln Ser Ile Thr Phe Asp Arg Ala Gly Gly Asn Ser Ser Leu Ala65 70 75 80Lys Val Glu Phe Gln Thr Ser Lys Gly Ala Ile Arg Tyr Gln Leu Tyr 85 90 95Leu Gly Asn Gly Lys Ile Lys Arg Ile Lys Glu Thr Lys Asn 100 105 110145196DNAStreptococcus pneumoniae 145gggacaaatt caaaaaaata ggcaagagga agcaaaaatc ttgcaaaagg aagaagtctt 60gagggtagct aagatggccc tgcagacggg gcaaaatcag gtaagcatca acggagttga 120gattcaggta ttttctagtg aaaaaggatt ggaggtctac catggttcag aacagttgtt 180ggcaatcaaa gagcca 19614665PRTStreptococcus pneumoniae 146Gly Gln Ile Gln Lys Asn Arg Gln Glu Glu Ala Lys Ile Leu Gln Lys1 5 10 15Glu Glu Val Leu Arg Val Ala Lys Met Ala Leu Gln Thr Gly Gln Asn 20 25 30Gln Val Ser Ile Asn Gly Val Glu Ile Gln Val Phe Ser Ser Glu Lys 35 40 45Gly Leu Glu Val Tyr His Gly Ser Glu Gln Leu Leu Ala Ile Lys Glu 50 55 60Pro65147319DNAStreptococcus pneumoniae 147tcgctaccag caacaaagcg agcaaaagga gtggctcttg tttgtggacc aacttgaggt 60agaattagac cgttcgcagt tcgaaaaagt agaaggcaat cgcctataca tgaagcaaga 120tggcaaggac atcgccatcg gtaagtcaaa gtcagatgat ttccgtaaaa cgaatgctcg 180tggtcgaggt tatcagccta tggtttatgg actcaaatct gtacggatta cagaggacaa 240tcaactggtt cgctttcatt tccagttcca aaaaggctta gaaagggagt tcatctatcg 300tgtggaaaaa gaaaaaagt 319148106PRTStreptococcus pneumoniae 148Arg Tyr Gln Gln Gln Ser Glu Gln Lys Glu Trp Leu Leu Phe Val Asp1 5 10 15Gln Leu Glu Val Glu Leu Asp Arg Ser Gln Phe Glu Lys Val Glu Gly 20 25 30Asn Arg Leu Tyr Met Lys Gln Asp Gly Lys Asp Ile Ala Ile Gly Lys 35 40 45Ser Lys Ser Asp Asp Phe Arg Lys Thr Asn Ala Arg Gly Arg Gly Tyr 50 55 60Gln Pro Met Val Tyr Gly Leu Lys Ser Val Arg Ile Thr Glu Asp Asn65 70 75 80Gln Leu Val Arg Phe His Phe Gln Phe Gln Lys Gly Leu Glu Arg Glu 85 90 95Phe Ile Tyr Arg Val Glu Lys Glu Lys Ser 100 105149322DNAStreptococcus pneumoniae 149gaaccgacaa gtcgcccact atcaagacta tgctttgaat aaagaaaaat tggttgcttt 60tgctatggct aaacgaacca aagataaggt tgagcaagaa agtggggaac agttttttaa 120tctaggtcag gtaagctatc aaaacaagaa aactggctta gtgacgaggg ttcgtacgga 180taagagccaa tatgagtttc tgtttccttc agtcaaaatc aaagaagaga aaagagataa 240aaaggaagag gtagcgaccg attcaagcga aaaagtggag aagaaaaaat cagaagagaa 300gcctgaaaag aaagagaatt ca 322150107PRTStreptococcus pneumoniae 150Asn Arg Gln Val Ala His Tyr Gln Asp Tyr Ala Leu Asn Lys Glu Lys1 5 10 15Leu Val Ala Phe Ala Met Ala Lys Arg Thr Lys Asp Lys Val Glu Gln 20 25 30Glu Ser Gly Glu Gln Phe Phe Asn Leu Gly Gln Val Ser Tyr Gln Asn 35 40 45Lys Lys Thr Gly Leu Val Thr Arg Val Arg Thr Asp Lys Ser Gln Tyr 50 55 60Glu Phe Leu Phe Pro Ser Val Lys Ile Lys Glu Glu Lys Arg Asp Lys65 70 75 80Lys Glu Glu Val Ala Thr Asp Ser Ser Glu Lys Val Glu Lys Lys Lys 85 90 95Ser Glu Glu Lys Pro Glu Lys Lys Glu Asn Ser 100 105151784DNAStreptococcus pneumoniae 151ggttgtcggc tggcaatata tcccgtttcc atctaaaggt agtacaattg gtccttaccc 60aaatggtatc agattagaag gttttccaaa gtcagagtgg tactacttcg ataaaaatgg 120agtgctacaa gagtttgttg gttggaaaac attagagatt aaaactaaag acagtgttgg 180aagaaagtac ggggaaaaac gtgaagattc agaagataaa gaagagaagc gttattatac 240gaactattac tttaatcaaa atcattcttt agagacaggt tggctttatg atcagtctaa 300ctggtattat ctagctaaga cggaaattaa tggagaaaac taccttggtg gtgaaagacg 360tgcggggtgg ataaacgatg attcgacttg gtactaccta gatccaacaa ctggtattat 420gcaaacaggt tggcaatatc taggtaataa gtggtactac ctccgttcct caggagcaat 480ggccactggc tggtatcagg aaggtaccac ttggtattat ttagaccacc caaatggcga 540tatgaaaaca ggttggcaaa accttgggaa caaatggtac tatctccgtt catcaggagc 600tatggcaact ggttggtatc aagatggttc aacttggtac tacctaaatg caggtaatgg 660agacatgaag acaggttggt tccaggtcaa tggcaactgg tactatgctt atagctcagg 720tgctttggca gtgaatacga ccgtagatgg ctattctgtc aactataatg gcgaatgggt 780tcgg 784152261PRTStreptococcus pneumoniae 152Val Val Gly Trp Gln Tyr Ile Pro Phe Pro Ser Lys Gly Ser Thr Ile1 5 10 15Gly Pro Tyr Pro Asn Gly Ile Arg Leu Glu Gly Phe Pro Lys Ser Glu 20 25 30Trp Tyr Tyr Phe Asp Lys Asn Gly Val Leu Gln Glu Phe Val Gly Trp 35 40 45Lys Thr Leu Glu Ile Lys Thr Lys Asp Ser Val Gly Arg Lys Tyr Gly 50 55 60Glu Lys Arg Glu Asp Ser Glu Asp Lys Glu Glu Lys Arg Tyr Tyr Thr65 70 75 80Asn Tyr Tyr Phe Asn Gln Asn His Ser Leu Glu Thr Gly Trp Leu Tyr 85 90 95Asp Gln Ser Asn Trp Tyr Tyr Leu Ala Lys Thr Glu Ile Asn Gly Glu 100 105 110Asn Tyr Leu Gly Gly Glu Arg Arg Ala Gly Trp Ile Asn Asp Asp Ser 115 120 125Thr Trp Tyr Tyr Leu Asp Pro Thr Thr Gly Ile Met Gln Thr Gly Trp 130 135 140Gln Tyr Leu Gly Asn Lys Trp Tyr Tyr Leu Arg Ser Ser Gly Ala Met145 150 155 160Ala Thr Gly Trp Tyr Gln Glu Gly Thr Thr Trp Tyr Tyr Leu Asp His 165 170 175Pro Asn Gly Asp Met Lys Thr Gly Trp Gln Asn Leu Gly Asn Lys Trp 180 185 190Tyr Tyr Leu Arg Ser Ser Gly Ala Met Ala Thr Gly Trp Tyr Gln Asp 195 200 205Gly Ser Thr Trp Tyr Tyr Leu Asn Ala Gly Asn Gly Asp Met Lys Thr 210 215 220Gly Trp Phe Gln Val Asn Gly Asn Trp Tyr Tyr Ala Tyr Ser Ser Gly225 230 235 240Ala Leu Ala Val Asn Thr Thr Val Asp Gly Tyr Ser Val Asn Tyr Asn 245 250 255Gly Glu Trp Val Arg 2601531708DNAStreptococcus pneumoniae 153ggccaaatca gaatgggtag aagacaaggg agccttttat tatcttgacc aagatggaaa 60gatgaaaaga aatgcttggg taggaacttc ctatgttggt gcaacaggtg ccaaagtaat 120agaagactgg gtctatgatt ctcaatacga tgcttggttt tatatcaaag cagatggaca 180gcacgcagag aaagaatggc tccaaattaa agggaaggac tattatttca aatccggtgg 240ttatctactg acaagtcagt ggattaatca agcttatgtg aatgctagtg gtgccaaagt 300acagcaaggt tggctttttg acaaacaata ccaatcttgg ttttacatca aagaaaatgg 360aaactatgct gataaagaat ggattttcga gaatggtcac tattattatc taaaatccgg 420tggctacatg gcagccaatg aatggatttg ggataaggaa tcttggtttt atctcaaatt 480tgatgggaaa atggctgaaa aagaatgggt ctacgattct catagtcaag cttggtacta 540cttcaaatcc ggtggttaca tgacagccaa tgaatggatt tgggataagg aatcttggtt 600ttatctcaaa tctgatggga aaatagctga aaaagaatgg gtctacgatt ctcatagtca 660agcttggtac tacttcaaat ccggtggtta catgacagcc aatgaatgga tttgggataa 720ggaatcttgg ttttacctca aatctgatgg gaaaatagct gaaaaagaat gggtctacga 780ttctcatagt caagcttggt actacttcaa atctggtggc tacatggcga aaaatgagac 840agtagatggt tatcagcttg gaagcgatgg taaatggctt ggaggaaaaa ctacaaatga 900aaatgctgct tactatcaag tagtgcctgt tacagccaat gtttatgatt cagatggtga 960aaagctttcc tatatatcgc aaggtagtgt cgtatggcta gataaggata gaaaaagtga 1020tgacaagcgc ttggctatta ctatttctgg tttgtcaggc tatatgaaaa cagaagattt 1080acaagcgcta gatgctagta aggactttat cccttattat gagagtgatg gccaccgttt 1140ttatcactat gtggctcaga atgctagtat cccagtagct tctcatcttt ctgatatgga 1200agtaggcaag aaatattatt cggcagatgg cctgcatttt gatggtttta agcttgagaa 1260tcccttcctt ttcaaagatt taacagaggc tacaaactac agtgctgaag aattggataa 1320ggtatttagt ttgctaaaca ttaacaatag ccttttggag aacaagggcg ctacttttaa 1380ggaagccgaa gaacattacc atatcaatgc tctttatctc cttgcccata gtgccctaga 1440aagtaactgg ggaagaagta aaattgccaa agataagaat aatttctttg gcattacagc 1500ctatgatacg accccttacc tttctgctaa gacatttgat gatgtggata agggaatttt 1560aggtgcaacc aagtggatta aggaaaatta tatcgatagg ggaagaactt tccttggaaa 1620caaggcttct ggtatgaatg tggaatatgc ttcagaccct tattggggcg aaaaaattgc 1680tagtgtgatg atgaaaatca atgagaag 1708154569PRTStreptococcus pneumoniae 154Ala Lys Ser Glu Trp Val Glu Asp Lys Gly Ala Phe Tyr Tyr Leu Asp1 5 10 15Gln Asp Gly Lys Met Lys Arg Asn Ala Trp Val Gly Thr Ser Tyr Val 20 25 30Gly Ala Thr Gly Ala Lys Val Ile Glu Asp Trp Val Tyr Asp Ser Gln 35 40 45Tyr Asp Ala Trp Phe Tyr Ile Lys Ala Asp Gly Gln His Ala Glu Lys 50 55 60Glu Trp Leu Gln Ile Lys Gly Lys Asp Tyr Tyr Phe Lys Ser Gly Gly65 70 75 80Tyr Leu Leu Thr Ser Gln Trp Ile Asn Gln Ala Tyr Val Asn Ala Ser 85 90 95Gly Ala Lys Val Gln Gln Gly Trp Leu Phe Asp Lys Gln Tyr Gln Ser 100 105 110Trp Phe Tyr Ile Lys Glu Asn Gly Asn Tyr Ala Asp Lys Glu Trp Ile 115 120 125Phe Glu Asn Gly His Tyr Tyr Tyr Leu Lys Ser Gly Gly Tyr Met Ala 130 135 140Ala Asn Glu Trp Ile Trp Asp Lys Glu Ser Trp Phe Tyr Leu Lys Phe145 150 155 160Asp Gly Lys Met Ala Glu Lys Glu Trp Val Tyr Asp Ser His Ser Gln 165 170 175Ala Trp Tyr Tyr Phe Lys Ser Gly Gly Tyr Met Thr Ala Asn Glu Trp 180 185 190Ile Trp Asp Lys Glu Ser Trp Phe Tyr Leu Lys Ser Asp Gly Lys Ile 195 200 205Ala Glu Lys Glu Trp Val Tyr Asp Ser His Ser Gln Ala Trp Tyr Tyr 210 215 220Phe Lys Ser Gly Gly Tyr Met Thr Ala Asn Glu Trp Ile Trp Asp Lys225 230 235 240Glu Ser Trp Phe Tyr Leu Lys Ser Asp Gly Lys Ile Ala Glu Lys Glu 245 250 255Trp Val Tyr Asp Ser His Ser Gln Ala Trp Tyr Tyr Phe Lys Ser Gly 260 265 270Gly Tyr Met Ala Lys Asn Glu Thr Val Asp

Gly Tyr Gln Leu Gly Ser 275 280 285Asp Gly Lys Trp Leu Gly Gly Lys Thr Thr Asn Glu Asn Ala Ala Tyr 290 295 300Tyr Gln Val Val Pro Val Thr Ala Asn Val Tyr Asp Ser Asp Gly Glu305 310 315 320Lys Leu Ser Tyr Ile Ser Gln Gly Ser Val Val Trp Leu Asp Lys Asp 325 330 335Arg Lys Ser Asp Asp Lys Arg Leu Ala Ile Thr Ile Ser Gly Leu Ser 340 345 350Gly Tyr Met Lys Thr Glu Asp Leu Gln Ala Leu Asp Ala Ser Lys Asp 355 360 365Phe Ile Pro Tyr Tyr Glu Ser Asp Gly His Arg Phe Tyr His Tyr Val 370 375 380Ala Gln Asn Ala Ser Ile Pro Val Ala Ser His Leu Ser Asp Met Glu385 390 395 400Val Gly Lys Lys Tyr Tyr Ser Ala Asp Gly Leu His Phe Asp Gly Phe 405 410 415Lys Leu Glu Asn Pro Phe Leu Phe Lys Asp Leu Thr Glu Ala Thr Asn 420 425 430Tyr Ser Ala Glu Glu Leu Asp Lys Val Phe Ser Leu Leu Asn Ile Asn 435 440 445Asn Ser Leu Leu Glu Asn Lys Gly Ala Thr Phe Lys Glu Ala Glu Glu 450 455 460His Tyr His Ile Asn Ala Leu Tyr Leu Leu Ala His Ser Ala Leu Glu465 470 475 480Ser Asn Trp Gly Arg Ser Lys Ile Ala Lys Asp Lys Asn Asn Phe Phe 485 490 495Gly Ile Thr Ala Tyr Asp Thr Thr Pro Tyr Leu Ser Ala Lys Thr Phe 500 505 510Asp Asp Val Asp Lys Gly Ile Leu Gly Ala Thr Lys Trp Ile Lys Glu 515 520 525Asn Tyr Ile Asp Arg Gly Arg Thr Phe Leu Gly Asn Lys Ala Ser Gly 530 535 540Met Asn Val Glu Tyr Ala Ser Asp Pro Tyr Trp Gly Glu Lys Ile Ala545 550 555 560Ser Val Met Met Lys Ile Asn Glu Lys 565155946DNAStreptococcus pneumoniae 155atttgcagat gattctgaag gatggcagtt tgtccaagaa aatggtagaa cctactacaa 60aaagggggat ctaaaagaaa cctactggag agtgatagat gggaagtact attattttga 120tcctttatcc ggagagatgg ttgtcggctg gcaatatata cctgctccac acaagggggt 180tacgattggt ccttctccaa gaatagagat tgctcttaga ccagattggt tttattttgg 240tcaagatggt gtattacaag aatttgttgg caagcaagtt ttagaagcaa aaactgctac 300gaataccaac aaacatcatg gggaagaata tgatagccaa gcagagaaac gagtctatta 360ttttgaagat cagcgtagtt atcatacttt aaaaactggt tggatttatg aagagggtca 420ttggtattat ttacagaagg atggtggctt tgattcgcgc atcaacagat tgacggttgg 480agagctagca cgtggttggg ttaaggatta ccctcttacg tatgatgaag agaagctaaa 540agcagctcca tggtactatc taaatccagc aactggcatt atgcaaacag gttggcaata 600tctaggtaat agatggtact acctccattc gtcaggagct atggcaactg gctggtataa 660ggaaggctca acttggtact atctagatgc tgaaaatggt gatatgagaa ctggctggca 720aaaccttggg aacaaatggt actatctccg ttcatcagga gctatggcaa ctggttggta 780tcaggaaagt tcgacttggt actatctaaa tgcaagtaat ggagatatga aaacaggctg 840gttccaagtc aatggtaact ggtactatgc ctatgattca ggtgctttag ctgttaatac 900cacagtaggt ggttactact taaactataa tggtgaatgg gttaag 946156316PRTStreptococcus pneumoniae 156Val Phe Ala Asp Asp Ser Glu Gly Trp Gln Phe Val Gln Glu Asn Gly1 5 10 15Arg Thr Tyr Tyr Lys Lys Gly Asp Leu Lys Glu Thr Tyr Trp Arg Val 20 25 30Ile Asp Gly Lys Tyr Tyr Tyr Phe Asp Pro Leu Ser Gly Glu Met Val 35 40 45Val Gly Trp Gln Tyr Ile Pro Ala Pro His Lys Gly Val Thr Ile Gly 50 55 60Pro Ser Pro Arg Ile Glu Ile Ala Leu Arg Pro Asp Trp Phe Tyr Phe65 70 75 80Gly Gln Asp Gly Val Leu Gln Glu Phe Val Gly Lys Gln Val Leu Glu 85 90 95Ala Lys Thr Ala Thr Asn Thr Asn Lys His His Gly Glu Glu Tyr Asp 100 105 110Ser Gln Ala Glu Lys Arg Val Tyr Tyr Phe Glu Asp Gln Arg Ser Tyr 115 120 125His Thr Leu Lys Thr Gly Trp Ile Tyr Glu Glu Gly His Trp Tyr Tyr 130 135 140Leu Gln Lys Asp Gly Gly Phe Asp Ser Arg Ile Asn Arg Leu Thr Val145 150 155 160Gly Glu Leu Ala Arg Gly Trp Val Lys Asp Tyr Pro Leu Thr Tyr Asp 165 170 175Glu Glu Lys Leu Lys Ala Ala Pro Trp Tyr Tyr Leu Asn Pro Ala Thr 180 185 190Gly Ile Met Gln Thr Gly Trp Gln Tyr Leu Gly Asn Arg Trp Tyr Tyr 195 200 205Leu His Ser Ser Gly Ala Met Ala Thr Gly Trp Tyr Lys Glu Gly Ser 210 215 220Thr Trp Tyr Tyr Leu Asp Ala Glu Asn Gly Asp Met Arg Thr Gly Trp225 230 235 240Gln Asn Leu Gly Asn Lys Trp Tyr Tyr Leu Arg Ser Ser Gly Ala Met 245 250 255Ala Thr Gly Trp Tyr Gln Glu Ser Ser Thr Trp Tyr Tyr Leu Asn Ala 260 265 270Ser Asn Gly Asp Met Lys Thr Gly Trp Phe Gln Val Asn Gly Asn Trp 275 280 285Tyr Tyr Ala Tyr Asp Ser Gly Ala Leu Ala Val Asn Thr Thr Val Gly 290 295 300Gly Tyr Tyr Leu Asn Tyr Asn Gly Glu Trp Val Lys305 310 3151571415DNAStreptococcus pneumoniae 157tgtcgctgca aatgaaactg aagtagcaaa aacttcgcag gatacaacga cagcttcaag 60tagttcagag caaaatcagt cttctaataa aacgcaaacg agcgcagaag tacagactaa 120tgctgctgcc cactgggatg gggattatta tgtaaaggat gatggttcta aagctcaaag 180tgaatggatt tttgacaact actataaggc ttggttttat attaattcag atggtcgtta 240ctcgcagaat gaatggcatg gaaattacta cctgaaatca ggtggatata tggcccaaaa 300cgagtggatc tatgacagta attacaagag ttggttttat ctcaagtcag atggggctta 360tgctcatcaa gaatggcaat tgattggaaa taagtggtac tacttcaaga agtggggtta 420catggctaaa agccaatggc aaggaagtta tttcttgaat ggtcaaggag ctatgatgca 480aaatgaatgg ctsctatgat ccagcctatt ctgcttattt ttatctaaaa tccgatggaa 540cttatgctaa ccaagagtgg caaaaagtgg gcggcaaatg gtactatttc aagaagtggg 600gctatatggc tcggaatgag tggcaaggca actactattt gactggaagt ggtgccatgg 660cgactgacga agtgattatg gatggtactc gctatatctt tgcggcctct ggtgagctca 720aagaaaaaaa agatttgaat gtcggctggg ttcacagaga tggtaagcgc tatttcttta 780ataatagaga agaacaagtg ggaaccgaac atgctaagaa agtcattgat attagtgagc 840acaatggtcg tatcaatgat tggaaaaagg ttattgatga gaacgaagtg gatggtgtca 900ttgttcgtct aggttatagc ggtaaagaag acaaggaatt ggcgcataac attaaggagt 960taaaccgtct gggaattcct tatggtgtct atctctatac ctatgctgaa aatgagaccg 1020atgctgagag tgacgctaaa cagaccattg aacttataaa gaaatacaat atgaacctgt 1080cttaccctat ctattatgat gttgagaatt gggaatatgt aaataagagc aagagagctc 1140caagtgatac aggcacttgg gttaaaatca tcaacaagta catggacacg atgaagcagg 1200cgggttatca aaatgtgtat gtctatagct atcgtagttt attacagacg cgtttaaaac 1260acccagatat tttaaaacat gtaaactggg tagcggccta tacgaatgct ttagaatggg 1320aaaaccctca ttattcagga aaaaaaggtt ggcaatatac ctcttctgaa tacatgaaag 1380gaatccaagg gcgcgtagat gtcagcgttt ggtat 1415158471PRTStreptococcus pneumoniae 158Val Ala Ala Asn Glu Thr Glu Val Ala Lys Thr Ser Gln Asp Thr Thr1 5 10 15Thr Ala Ser Ser Ser Ser Glu Gln Asn Gln Ser Ser Asn Lys Thr Gln 20 25 30Thr Ser Ala Glu Val Gln Thr Asn Ala Ala Ala His Trp Asp Gly Asp 35 40 45Tyr Tyr Val Lys Asp Asp Gly Ser Lys Ala Gln Ser Glu Trp Ile Phe 50 55 60Asp Asn Tyr Tyr Lys Ala Trp Phe Tyr Ile Asn Ser Asp Gly Arg Tyr65 70 75 80Ser Gln Asn Glu Trp His Gly Asn Tyr Tyr Leu Lys Ser Gly Gly Tyr 85 90 95Met Ala Gln Asn Glu Trp Ile Tyr Asp Ser Asn Tyr Lys Ser Trp Phe 100 105 110Tyr Leu Lys Ser Asp Gly Ala Tyr Ala His Gln Glu Trp Gln Leu Ile 115 120 125Gly Asn Lys Trp Tyr Tyr Phe Lys Lys Trp Gly Tyr Met Ala Lys Ser 130 135 140Gln Trp Gln Gly Ser Tyr Phe Leu Asn Gly Gln Gly Ala Met Met Gln145 150 155 160Asn Glu Trp Leu Tyr Asp Pro Ala Tyr Ser Ala Tyr Phe Tyr Leu Lys 165 170 175Ser Asp Gly Thr Tyr Ala Asn Gln Glu Trp Gln Lys Val Gly Gly Lys 180 185 190Trp Tyr Tyr Phe Lys Lys Trp Gly Tyr Met Ala Arg Asn Glu Trp Gln 195 200 205Gly Asn Tyr Tyr Leu Thr Gly Ser Gly Ala Met Ala Thr Asp Glu Val 210 215 220Ile Met Asp Gly Thr Arg Tyr Ile Phe Ala Ala Ser Gly Glu Leu Lys225 230 235 240Glu Lys Lys Asp Leu Asn Val Gly Trp Val His Arg Asp Gly Lys Arg 245 250 255Tyr Phe Phe Asn Asn Arg Glu Glu Gln Val Gly Thr Glu His Ala Lys 260 265 270Lys Val Ile Asp Ile Ser Glu His Asn Gly Arg Ile Asn Asp Trp Lys 275 280 285Lys Val Ile Asp Glu Asn Glu Val Asp Gly Val Ile Val Arg Leu Gly 290 295 300Tyr Ser Gly Lys Glu Asp Lys Glu Leu Ala His Asn Ile Lys Glu Leu305 310 315 320Asn Arg Leu Gly Ile Pro Tyr Gly Val Tyr Leu Tyr Thr Tyr Ala Glu 325 330 335Asn Glu Thr Asp Ala Glu Ser Asp Ala Lys Gln Thr Ile Glu Leu Ile 340 345 350Lys Lys Tyr Asn Met Asn Leu Ser Tyr Pro Ile Tyr Tyr Asp Val Glu 355 360 365Asn Trp Glu Tyr Val Asn Lys Ser Lys Arg Ala Pro Ser Asp Thr Gly 370 375 380Thr Trp Val Lys Ile Ile Asn Lys Tyr Met Asp Thr Met Lys Gln Ala385 390 395 400Gly Tyr Gln Asn Val Tyr Val Tyr Ser Tyr Arg Ser Leu Leu Gln Thr 405 410 415Arg Leu Lys His Pro Asp Ile Leu Lys His Val Asn Trp Val Ala Ala 420 425 430Tyr Thr Asn Ala Leu Glu Trp Glu Asn Pro His Tyr Ser Gly Lys Lys 435 440 445Gly Trp Gln Tyr Thr Ser Ser Glu Tyr Met Lys Gly Ile Gln Gly Arg 450 455 460Val Asp Val Ser Val Trp Tyr465 4701591924DNAStreptococcus pneumoniaemisc_feature(917)..(917)n is a, c, g, or t 159tacgtctcag cctacttttg taagagcaga agaatctcca caagttgtcg aaaaatcttc 60attagagaag aaatatgagg aagcaaaagc aaaagctgat actgccaaga aagattacga 120aacggctaaa aagaaagcag aagacgctca gaaaaagtat gaagatgatc agaagagaac 180tgaggagaaa gctcgaaaag aagcagaagc atctcaaaaa ttgaatgatg tggcgcttgt 240tgttcaaaat gcatataaag agtaccgaga agttcaaaat caacgtagta aatataaatc 300tgacgctgaa tatcagaaaa aattaacaga ggtcgactct aaaatagaga aggctaggaa 360agagcaacag gacttgcaaa ataaatttaa tgaagtaaga gcagttgtag ttcctgaacc 420aaatgcgttg gctgagacta agaaaaaagc agaagaagct aaagcagaag aaaaagtagc 480taagagaaaa tatgattatg caactctaaa ggtagcacta gcgaagaaag aagtagaggc 540taaggaactt gaaattgaaa aacttcaata tgaaatttct actttggaac aagaagttgc 600tactgctcaa catcaagtag ataatttgaa aaaacttctt gctggtgcgg atcctgatga 660tggcacagaa gttatagaag ctaaattaaa aaaaggagaa gctgagctaa acgctaaaca 720agctgagtta gcaaaaaaac aaacagaact tgaaaaactt cttgacagcc ttgatcctga 780aggtaagact caggatgaat tagataaaga agcagaagaa gctgagttgg ataaaaaagc 840tgatgaactt caaaataaag ttgctgattt agaaaaagaa attagtaacc ttgaaatatt 900acttggaggg gctgatnctg aagatgatac tgctgctctt caaaataaat tagctactaa 960aaaagctgaa ttggaaaaaa ctcaaaaaga attagatgca gctcttaatg agttaggccc 1020tgatggagat gaagaagaaa ctccagcgcc ggctcctcaa ccagagcaac cagctcctgc 1080accaaaacca gagcaaccag ctccagctcc aaaaccagag caaccagctc ctgcaccaaa 1140accagagcaa ccagctccag ctccaaaacc agagcaacca gctccagctc caaaaccaga 1200gcaaccagct aagccggaga aaccagctga agagcctact caaccagaaa aaccagccac 1260tccaaaaaca ggctggaaac aagaaaacgg tatgtggtat ttctacaata ctgatggttc 1320aatggcaata ggttggctcc aaaacaacgg ttcatggtac tacctaaacg ctaacggcgc 1380tatggcaaca ggttgggtga aagatggaga tacctggtac tatcttgaag catcaggtgc 1440tatgaaagca agccaatggt tcaaagtatc agataaatgg tactatgtca acagcaatgg 1500cgctatggcg acaggctggc tccaatacaa tggctcatgg tactacctca acgctaatgg 1560tgatatggcg acaggatggc tccaatacaa cggttcatgg tattacctca acgctaatgg 1620tgatatggcg acaggatggg ctaaagtcaa cggttcatgg tactacctaa acgctaacgg 1680tgctatggct acaggttggg ctaaagtcaa cggttcatgg tactacctaa acgctaacgg 1740ttcaatggca acaggttggg tgaaagatgg agatacctgg tactatcttg aagcatcagg 1800tgctatgaaa gcaagccaat ggttcaaagt atcagataaa tggtactatg tcaatggctt 1860aggtgccctt gcagtcaaca caactgtaga tggctataaa gtcaatgcca atggtgaatg 1920ggtt 1924160641PRTStreptococcus pneumoniaeSITE(306)..(306)Xaa can be any naturally occurring amino acid 160Thr Ser Gln Pro Thr Phe Val Arg Ala Glu Glu Ser Pro Gln Val Val1 5 10 15Glu Lys Ser Ser Leu Glu Lys Lys Tyr Glu Glu Ala Lys Ala Lys Ala 20 25 30Asp Thr Ala Lys Lys Asp Tyr Glu Thr Ala Lys Lys Lys Ala Glu Asp 35 40 45Ala Gln Lys Lys Tyr Glu Asp Asp Gln Lys Arg Thr Glu Glu Lys Ala 50 55 60Arg Lys Glu Ala Glu Ala Ser Gln Lys Leu Asn Asp Val Ala Leu Val65 70 75 80Val Gln Asn Ala Tyr Lys Glu Tyr Arg Glu Val Gln Asn Gln Arg Ser 85 90 95Lys Tyr Lys Ser Asp Ala Glu Tyr Gln Lys Lys Leu Thr Glu Val Asp 100 105 110Ser Lys Ile Glu Lys Ala Arg Lys Glu Gln Gln Asp Leu Gln Asn Lys 115 120 125Phe Asn Glu Val Arg Ala Val Val Val Pro Glu Pro Asn Ala Leu Ala 130 135 140Glu Thr Lys Lys Lys Ala Glu Glu Ala Lys Ala Glu Glu Lys Val Ala145 150 155 160Lys Arg Lys Tyr Asp Tyr Ala Thr Leu Lys Val Ala Leu Ala Lys Lys 165 170 175Glu Val Glu Ala Lys Glu Leu Glu Ile Glu Lys Leu Gln Tyr Glu Ile 180 185 190Ser Thr Leu Glu Gln Glu Val Ala Thr Ala Gln His Gln Val Asp Asn 195 200 205Leu Lys Lys Leu Leu Ala Gly Ala Asp Pro Asp Asp Gly Thr Glu Val 210 215 220Ile Glu Ala Lys Leu Lys Lys Gly Glu Ala Glu Leu Asn Ala Lys Gln225 230 235 240Ala Glu Leu Ala Lys Lys Gln Thr Glu Leu Glu Lys Leu Leu Asp Ser 245 250 255Leu Asp Pro Glu Gly Lys Thr Gln Asp Glu Leu Asp Lys Glu Ala Glu 260 265 270Glu Ala Glu Leu Asp Lys Lys Ala Asp Glu Leu Gln Asn Lys Val Ala 275 280 285Asp Leu Glu Lys Glu Ile Ser Asn Leu Glu Ile Leu Leu Gly Gly Ala 290 295 300Asp Xaa Glu Asp Asp Thr Ala Ala Leu Gln Asn Lys Leu Ala Thr Lys305 310 315 320Lys Ala Glu Leu Glu Lys Thr Gln Lys Glu Leu Asp Ala Ala Leu Asn 325 330 335Glu Leu Gly Pro Asp Gly Asp Glu Glu Glu Thr Pro Ala Pro Ala Pro 340 345 350Gln Pro Glu Gln Pro Ala Pro Ala Pro Lys Pro Glu Gln Pro Ala Pro 355 360 365Ala Pro Lys Pro Glu Gln Pro Ala Pro Ala Pro Lys Pro Glu Gln Pro 370 375 380Ala Pro Ala Pro Lys Pro Glu Gln Pro Ala Pro Ala Pro Lys Pro Glu385 390 395 400Gln Pro Ala Lys Pro Glu Lys Pro Ala Glu Glu Pro Thr Gln Pro Glu 405 410 415Lys Pro Ala Thr Pro Lys Thr Gly Trp Lys Gln Glu Asn Gly Met Trp 420 425 430Tyr Phe Tyr Asn Thr Asp Gly Ser Met Ala Ile Gly Trp Leu Gln Asn 435 440 445Asn Gly Ser Trp Tyr Tyr Leu Asn Ala Asn Gly Ala Met Ala Thr Gly 450 455 460Trp Val Lys Asp Gly Asp Thr Trp Tyr Tyr Leu Glu Ala Ser Gly Ala465 470 475 480Met Lys Ala Ser Gln Trp Phe Lys Val Ser Asp Lys Trp Tyr Tyr Val 485 490 495Asn Ser Asn Gly Ala Met Ala Thr Gly Trp Leu Gln Tyr Asn Gly Ser 500 505 510Trp Tyr Tyr Leu Asn Ala Asn Gly Asp Met Ala Thr Gly Trp Leu Gln 515 520 525Tyr Asn Gly Ser Trp Tyr Tyr Leu Asn Ala Asn Gly Asp Met Ala Thr 530 535 540Gly Trp Ala Lys Val Asn Gly Ser Trp Tyr Tyr Leu Asn Ala Asn Gly545 550 555 560Ala Met Ala Thr Gly Trp Ala Lys Val Asn Gly Ser Trp Tyr Tyr Leu 565 570 575Asn Ala Asn Gly Ser Met Ala Thr Gly Trp Val Lys Asp Gly Asp Thr 580 585 590Trp Tyr Tyr Leu Glu Ala Ser Gly Ala Met Lys Ala Ser Gln Trp Phe 595 600 605Lys Val Ser Asp Lys Trp Tyr Tyr Val Asn Gly Leu Gly Ala Leu Ala 610 615 620Val Asn Thr Thr Val Asp Gly Tyr Lys Val Asn Ala Asn Gly Glu Trp625 630

635 640Val161670DNAStreptococcus pneumoniaemisc_feature(99)..(99)n is a, c, g, or t 161tggacaggtg aaaggtcatg ctacatttgt gaaatccatg acaactgaaa tgtaccaaga 60acaacagaac cattctctcg cctacaatca acgcttggnt tcgcaaaatc gcattgtaga 120tccttttttg gcggagggat atgaggtcaa ttaccaagtg tctgacgacc ctgatgcagt 180ctatggttac ttgtctattc caagtttgga aatcatggag ccggtttatt tgggagcaga 240ttatcatcat ttagggatgg gcttggctca tgtggatggt acaccgctgc ctctggatgg 300tacagggatt cgctcagtga ttgctgggca ccgtgcagag ccaagccatg tctttttccg 360ccatttggat cagctaaaag ttggagatgc tctttattat gataatggcc aggaaattgt 420agaatatcag atgatggaca cagagattat tttaccgtcg gaatgggaaa aattagaatc 480ggttagctct aaaaatatca tgaccttgat aacctgcgat ccgattccta cctttaataa 540acgcttatta gtgaattttg aacgagtcgc tgtttatcaa aaatcagatc cacaaacagc 600tgcagttgcg agggttgctt ttacgaaaga aggacaatct gtatcgcgtg ttgcaacctc 660tcaatggttg 670162223PRTStreptococcus pneumoniaeSITE(33)..(33)Xaa can be any naturally occurring amino acid 162Gly Gln Val Lys Gly His Ala Thr Phe Val Lys Ser Met Thr Thr Glu1 5 10 15Met Tyr Gln Glu Gln Gln Asn His Ser Leu Ala Tyr Asn Gln Arg Leu 20 25 30Xaa Ser Gln Asn Arg Ile Val Asp Pro Phe Leu Ala Glu Gly Tyr Glu 35 40 45Val Asn Tyr Gln Val Ser Asp Asp Pro Asp Ala Val Tyr Gly Tyr Leu 50 55 60Ser Ile Pro Ser Leu Glu Ile Met Glu Pro Val Tyr Leu Gly Ala Asp65 70 75 80Tyr His His Leu Gly Met Gly Leu Ala His Val Asp Gly Thr Pro Leu 85 90 95Pro Leu Asp Gly Thr Gly Ile Arg Ser Val Ile Ala Gly His Arg Ala 100 105 110Glu Pro Ser His Val Phe Phe Arg His Leu Asp Gln Leu Lys Val Gly 115 120 125Asp Ala Leu Tyr Tyr Asp Asn Gly Gln Glu Ile Val Glu Tyr Gln Met 130 135 140Met Asp Thr Glu Ile Ile Leu Pro Ser Glu Trp Glu Lys Leu Glu Ser145 150 155 160Val Ser Ser Lys Asn Ile Met Thr Leu Ile Thr Cys Asp Pro Ile Pro 165 170 175Thr Phe Asn Lys Arg Leu Leu Val Asn Phe Glu Arg Val Ala Val Tyr 180 185 190Gln Lys Ser Asp Pro Gln Thr Ala Ala Val Ala Arg Val Ala Phe Thr 195 200 205Lys Glu Gly Gln Ser Val Ser Arg Val Ala Thr Ser Gln Trp Leu 210 215 220163784DNAStreptococcus pneumoniae 163gattgctcct ttgaaggatt tgagagaaac catgttggaa attgcttctg gtgctcaaaa 60tcttcgtgcc aaggaagttg gtgcctatga actgagagaa gtaactcgcc aatttaatgc 120tatgttggat cagattgatc agttgatggt agctattcgt agccaggaag aaacgacccg 180tcagtaccaa cttcaagccc tttcgagcca gattaatcca catttcctct ataacacttt 240ggacaccatc atctggatgg ctgaatttca tgatagtcag cgagtggtgc aggtgaccaa 300gtccttggca acctatttcc gcttggcgct caatcaaggc aaggacttga tttgtctctc 360tgacgaaatc aatcatgtcc gccagtatct ctttatccag aaacaacgct atggagataa 420gctggaatac gaaattaatg aaaatgttgc ctttgataat ttagtcttac ccaagctggt 480cctacaaccc cttgtagaaa atgctcttta ccatggcatt aaggaaaagg aaggtcaggg 540ccatattaaa ctttctgtcc agaaacagga ttcgggattg gtcatccgta ttgaggatga 600tggcgttggc ttccaagatg ctggtgatag tagtcaaagt caactcaaac gtgggggagt 660tggtcttcaa aatgtcgatc aacggctcaa acttcatttt ggagccaatt accatatgaa 720gattgattct agaccccaaa aagggacgaa agttgaaata tatataaata gaatagaaac 780tagc 784164261PRTStreptococcus pneumoniae 164Ile Ala Pro Leu Lys Asp Leu Arg Glu Thr Met Leu Glu Ile Ala Ser1 5 10 15Gly Ala Gln Asn Leu Arg Ala Lys Glu Val Gly Ala Tyr Glu Leu Arg 20 25 30Glu Val Thr Arg Gln Phe Asn Ala Met Leu Asp Gln Ile Asp Gln Leu 35 40 45Met Val Ala Ile Arg Ser Gln Glu Glu Thr Thr Arg Gln Tyr Gln Leu 50 55 60Gln Ala Leu Ser Ser Gln Ile Asn Pro His Phe Leu Tyr Asn Thr Leu65 70 75 80Asp Thr Ile Ile Trp Met Ala Glu Phe His Asp Ser Gln Arg Val Val 85 90 95Gln Val Thr Lys Ser Leu Ala Thr Tyr Phe Arg Leu Ala Leu Asn Gln 100 105 110Gly Lys Asp Leu Ile Cys Leu Ser Asp Glu Ile Asn His Val Arg Gln 115 120 125Tyr Leu Phe Ile Gln Lys Gln Arg Tyr Gly Asp Lys Leu Glu Tyr Glu 130 135 140Ile Asn Glu Asn Val Ala Phe Asp Asn Leu Val Leu Pro Lys Leu Val145 150 155 160Leu Gln Pro Leu Val Glu Asn Ala Leu Tyr His Gly Ile Lys Glu Lys 165 170 175Glu Gly Gln Gly His Ile Lys Leu Ser Val Gln Lys Gln Asp Ser Gly 180 185 190Leu Val Ile Arg Ile Glu Asp Asp Gly Val Gly Phe Gln Asp Ala Gly 195 200 205Asp Ser Ser Gln Ser Gln Leu Lys Arg Gly Gly Val Gly Leu Gln Asn 210 215 220Val Asp Gln Arg Leu Lys Leu His Phe Gly Ala Asn Tyr His Met Lys225 230 235 240Ile Asp Ser Arg Pro Gln Lys Gly Thr Lys Val Glu Ile Tyr Ile Asn 245 250 255Arg Ile Glu Thr Ser 260165325DNAStreptococcus pneumoniae 165taggtcatat gggacttttt ttctacaaca aaataggctc cataatatct ataagggatt 60tacccactac aaatattata gagccgaaaa ttcacatcta atatatgcag actactttga 120aatgaaatta aaaaaattat taaaggatga cacaaaagtt tttgaaaaat ctacattcaa 180atttgtagaa ggatataaaa tatacctgac agaatctaaa gaatctggaa ttaaacaaat 240ggacaatgtc ataaaatatt ttgagtttat tgaatctaaa agtattgctt tatattttca 300aaaacgatta aatgagctga tagat 325166108PRTStreptococcus pneumoniae 166Arg Ser Tyr Gly Thr Phe Phe Leu Gln Gln Asn Arg Leu His Asn Ile1 5 10 15Tyr Lys Gly Phe Thr His Tyr Lys Tyr Tyr Arg Ala Glu Asn Ser His 20 25 30Leu Ile Tyr Ala Asp Tyr Phe Glu Met Lys Leu Lys Lys Leu Leu Lys 35 40 45Asp Asp Thr Lys Val Phe Glu Lys Ser Thr Phe Lys Phe Val Glu Gly 50 55 60Tyr Lys Ile Tyr Leu Thr Glu Ser Lys Glu Ser Gly Ile Lys Gln Met65 70 75 80Asp Asn Val Ile Lys Tyr Phe Glu Phe Ile Glu Ser Lys Ser Ile Ala 85 90 95Leu Tyr Phe Gln Lys Arg Leu Asn Glu Leu Ile Asp 100 105167238DNAStreptococcus pneumoniae 167caacgttgag aattatttgc gaatgtgttt ggatagcatt cagaatcaga cgtatcaaaa 60ttttgagtgt ttattaatca atgatggctc tccagatcat tcatccaaaa tatgtgaaga 120atttgtagag aaagattctc gtttcaaata ttttgagaaa gcaaacggcg gtctttcatc 180agctcgtaac ctaggtattg aatgttcggg ggggggcgta cattactttt gtagactc 23816879PRTStreptococcus pneumoniae 168Asn Val Glu Asn Tyr Leu Arg Met Cys Leu Asp Ser Ile Gln Asn Gln1 5 10 15Thr Tyr Gln Asn Phe Glu Cys Leu Leu Ile Asn Asp Gly Ser Pro Asp 20 25 30His Ser Ser Lys Ile Cys Glu Glu Phe Val Glu Lys Asp Ser Arg Phe 35 40 45Lys Tyr Phe Glu Lys Ala Asn Gly Gly Leu Ser Ser Ala Arg Asn Leu 50 55 60Gly Ile Glu Cys Ser Gly Gly Gly Val His Tyr Phe Cys Arg Leu65 70 75169742DNAStreptococcus pneumoniae 169ctactatcaa tcaagttctt cagccattga ggccaccatt gagggcaaca gccaaacgac 60catcagccag actagccact ttattcagtc ttatatcaaa aaactagaaa ccacctcgac 120tggtttgacc cagcagacgg atgttctggc ctatgctgag aatcccagtc aagacaaggt 180cgagggaatc cgagatttgt ttttgaccat cttgaagtca gataaggact tgaaaactgt 240tgtgctggtg accaaatctg gtcaggtcat ttctacagat gacagtgtgc agatgaaaac 300ttcctctgat atgatggctg aggattggta ccaaaaggcc attcatcagg gagctatgcc 360tgttttgact ccagctcgta aatcagatag tcagtgggtc atttctgtca ctcaagaact 420tgttgatgca aagggagcca atcttggtgt gcttcgtttg gatatttctt atgaaactct 480ggaagcctat ctcaatcaac tccagttggg gcagcagggc tttgccttca ttatcaatga 540aaaccatgaa tttgtctacc atcctcaaca cacagtttat agttcgtcta gcaaaatgga 600ggctatgaaa ccctacatcg atacaggtca gggttatact cctggtcaca aatcctacgt 660cagtcaagag aagattgcag gaactgattg gacggtgctt ggcgtgtcat cattggaaaa 720gttagaccag gttcggagtc ag 742170247PRTStreptococcus pneumoniae 170Tyr Tyr Gln Ser Ser Ser Ser Ala Ile Glu Ala Thr Ile Glu Gly Asn1 5 10 15Ser Gln Thr Thr Ile Ser Gln Thr Ser His Phe Ile Gln Ser Tyr Ile 20 25 30Lys Lys Leu Glu Thr Thr Ser Thr Gly Leu Thr Gln Gln Thr Asp Val 35 40 45Leu Ala Tyr Ala Glu Asn Pro Ser Gln Asp Lys Val Glu Gly Ile Arg 50 55 60Asp Leu Phe Leu Thr Ile Leu Lys Ser Asp Lys Asp Leu Lys Thr Val65 70 75 80Val Leu Val Thr Lys Ser Gly Gln Val Ile Ser Thr Asp Asp Ser Val 85 90 95Gln Met Lys Thr Ser Ser Asp Met Met Ala Glu Asp Trp Tyr Gln Lys 100 105 110Ala Ile His Gln Gly Ala Met Pro Val Leu Thr Pro Ala Arg Lys Ser 115 120 125Asp Ser Gln Trp Val Ile Ser Val Thr Gln Glu Leu Val Asp Ala Lys 130 135 140Gly Ala Asn Leu Gly Val Leu Arg Leu Asp Ile Ser Tyr Glu Thr Leu145 150 155 160Glu Ala Tyr Leu Asn Gln Leu Gln Leu Gly Gln Gln Gly Phe Ala Phe 165 170 175Ile Ile Asn Glu Asn His Glu Phe Val Tyr His Pro Gln His Thr Val 180 185 190Tyr Ser Ser Ser Ser Lys Met Glu Ala Met Lys Pro Tyr Ile Asp Thr 195 200 205Gly Gln Gly Tyr Thr Pro Gly His Lys Ser Tyr Val Ser Gln Glu Lys 210 215 220Ile Ala Gly Thr Asp Trp Thr Val Leu Gly Val Ser Ser Leu Glu Lys225 230 235 240Leu Asp Gln Val Arg Ser Gln 2451711282DNAStreptococcus pneumoniaemisc_feature(712)..(712)n is a, c, g, or t 171gacaaaaaca ttaaaacgtc ctgaggtttt atcacctgca gggactttag agaagctaaa 60ggtagctgtt cagtatggag cagatgctgt ctttatcggt ggtcaggcct atggtcttcg 120tagccgtgcg ggaaacttta ctttcgaaca gatggaagaa ggcgtgcagt ttgcggccaa 180gtatggtgcc aaggtctatg tagcggctaa tatggttatg cacgaaggaa atgaagctgg 240tgctggtgag tggttccgta aactgcgtga tatcgggatt gcagcagtta tcgtatctga 300cccagccttg attatgattg cagtgactga agcaccaggc cttgaaatcc acctttctac 360ccaagccagt gccactaact atgaaaccct tgagttctgg aaagagctag gcttgactcg 420tgtcgtttta gcgcgtgagg tttcaatgga agaattagct gagatccgca aacgtacaga 480tgttgaaatt gaagcctttg tccatggagc tatgtgtatt tcatactctg gacgttgtac 540tctttcaaac cacatgagta tgcgtgatgc caaccgtggt ggatgttctc agtcatgccg 600ttggaaatac gacctttacg atatgccatt tgggaaagaa cgtaagagtt tgcagggtga 660gattccagaa gaattttcaa tgtcagccgt tgacatgtct atgattgacc anattccaga 720tatgattgaa aatggtgtgg acagtctaaa aatcgaagga cgtatgnagt ctattcacta 780ngtatcaaca gtaaccaact gctacaaggc ggctgtggat gcctatcttg aaagtcctga 840aaagtttgaa gctatcaaac aagacttggt ggacgagatg tggaaggttg cccaacgtga 900actggctaca ggattttact atggtacacc atctgaaaat gagcagttgt ttggtgctcg 960tcgtaaaatc cctgagtaca agtttgtcgc tgaagtggtt tcttatgatg atgcggcaca 1020aacagcaact attcgtcaac gaaacgtcat taacgaaggg gaccaagttg agttttatgg 1080tccaggtttc cgtcattttg aaacctatat tgaagatttg catgatgcta aaggcaataa 1140aatcgaccgc gctccaaatc caatggaact attgactatt aaagtcccac aacctgttca 1200atcaggagac atggttcgag ctcttaaaga ggggcttatc aatctttata aggaagatgg 1260aaccagcgtc acagttcgtg ct 1282172427PRTStreptococcus pneumoniaeSITE(237)..(237)Xaa can be any naturally occurring amino acid 172Thr Lys Thr Leu Lys Arg Pro Glu Val Leu Ser Pro Ala Gly Thr Leu1 5 10 15Glu Lys Leu Lys Val Ala Val Gln Tyr Gly Ala Asp Ala Val Phe Ile 20 25 30Gly Gly Gln Ala Tyr Gly Leu Arg Ser Arg Ala Gly Asn Phe Thr Phe 35 40 45Glu Gln Met Glu Glu Gly Val Gln Phe Ala Ala Lys Tyr Gly Ala Lys 50 55 60Val Tyr Val Ala Ala Asn Met Val Met His Glu Gly Asn Glu Ala Gly65 70 75 80Ala Gly Glu Trp Phe Arg Lys Leu Arg Asp Ile Gly Ile Ala Ala Val 85 90 95Ile Val Ser Asp Pro Ala Leu Ile Met Ile Ala Val Thr Glu Ala Pro 100 105 110Gly Leu Glu Ile His Leu Ser Thr Gln Ala Ser Ala Thr Asn Tyr Glu 115 120 125Thr Leu Glu Phe Trp Lys Glu Leu Gly Leu Thr Arg Val Val Leu Ala 130 135 140Arg Glu Val Ser Met Glu Glu Leu Ala Glu Ile Arg Lys Arg Thr Asp145 150 155 160Val Glu Ile Glu Ala Phe Val His Gly Ala Met Cys Ile Ser Tyr Ser 165 170 175Gly Arg Cys Thr Leu Ser Asn His Met Ser Met Arg Asp Ala Asn Arg 180 185 190Gly Gly Cys Ser Gln Ser Cys Arg Trp Lys Tyr Asp Leu Tyr Asp Met 195 200 205Pro Phe Gly Lys Glu Arg Lys Ser Leu Gln Gly Glu Ile Pro Glu Glu 210 215 220Phe Ser Met Ser Ala Val Asp Met Ser Met Ile Asp Xaa Ile Pro Asp225 230 235 240Met Ile Glu Asn Gly Val Asp Ser Leu Lys Ile Glu Gly Arg Met Xaa 245 250 255Ser Ile His Xaa Val Ser Thr Val Thr Asn Cys Tyr Lys Ala Ala Val 260 265 270Asp Ala Tyr Leu Glu Ser Pro Glu Lys Phe Glu Ala Ile Lys Gln Asp 275 280 285Leu Val Asp Glu Met Trp Lys Val Ala Gln Arg Glu Leu Ala Thr Gly 290 295 300Phe Tyr Tyr Gly Thr Pro Ser Glu Asn Glu Gln Leu Phe Gly Ala Arg305 310 315 320Arg Lys Ile Pro Glu Tyr Lys Phe Val Ala Glu Val Val Ser Tyr Asp 325 330 335Asp Ala Ala Gln Thr Ala Thr Ile Arg Gln Arg Asn Val Ile Asn Glu 340 345 350Gly Asp Gln Val Glu Phe Tyr Gly Pro Gly Phe Arg His Phe Glu Thr 355 360 365Tyr Ile Glu Asp Leu His Asp Ala Lys Gly Asn Lys Ile Asp Arg Ala 370 375 380Pro Asn Pro Met Glu Leu Leu Thr Ile Lys Val Pro Gln Pro Val Gln385 390 395 400Ser Gly Asp Met Val Arg Ala Leu Lys Glu Gly Leu Ile Asn Leu Tyr 405 410 415Lys Glu Asp Gly Thr Ser Val Thr Val Arg Ala 420 425173778DNAStreptococcus pneumoniae 173ttctcaggag acctttaaaa atatcaccaa tagcttctcc atgcaaatca atcgtcgcgt 60caaccaagga acgcctcgtg gtgctgggaa tatcaagggt gaagacatca aaaaaatcac 120cgaaaacaag gccattgagt cttatgtcaa acgtatcaac gctatcggag atttgactgg 180atatgacctg attgaaacgc cagaaaccaa gaagaatctc actgctgatc gtgccaagcg 240ttttggaagt agcttgatga ttacaggtgt caatgactcc tctaaagaag acaagtttgt 300ctctggttct tataaactag tcgaaggaga gcacttaacc aacgacgaca aggataaaat 360cctcttgcac aaggacttgg cagccaaaca cggctggaaa gtaggggaca aggttaaact 420ggactctaat atctacgatg cagataatga aaaaggagcc aaggaaacag ttgaagtgac 480aatcaaggga ctctttgatg gtcataataa gtcagcagta acctactcac aagaacttta 540cgaaaacaca gctattacag acattcacac tgctgcaaaa ctttatggat acacagaaga 600cacagccatt tatggggacg caaccttctt tgtaacagca gacaagaact tggatgatgt 660tatgaaagag ttgaatggca tcagtggtat caactggaag agctacacac tcgtcaagag 720ctcctctaac tacccagctc ttgagcaatc tatctctggt atgtacaaga tggccaac 778174259PRTStreptococcus pneumoniae 174Ser Gln Glu Thr Phe Lys Asn Ile Thr Asn Ser Phe Ser Met Gln Ile1 5 10 15Asn Arg Arg Val Asn Gln Gly Thr Pro Arg Gly Ala Gly Asn Ile Lys 20 25 30Gly Glu Asp Ile Lys Lys Ile Thr Glu Asn Lys Ala Ile Glu Ser Tyr 35 40 45Val Lys Arg Ile Asn Ala Ile Gly Asp Leu Thr Gly Tyr Asp Leu Ile 50 55 60Glu Thr Pro Glu Thr Lys Lys Asn Leu Thr Ala Asp Arg Ala Lys Arg65 70 75 80Phe Gly Ser Ser Leu Met Ile Thr Gly Val Asn Asp Ser Ser Lys Glu 85 90 95Asp Lys Phe Val Ser Gly Ser Tyr Lys Leu Val Glu Gly Glu His Leu 100 105 110Thr Asn Asp Asp Lys Asp Lys Ile Leu Leu His Lys Asp Leu Ala Ala 115 120 125Lys His Gly Trp Lys Val Gly Asp Lys Val Lys Leu Asp Ser Asn Ile 130 135 140Tyr Asp Ala Asp Asn Glu Lys Gly Ala Lys Glu Thr Val Glu Val Thr145 150 155 160Ile Lys Gly Leu Phe Asp Gly His Asn Lys Ser Ala Val Thr Tyr Ser 165 170 175Gln Glu Leu Tyr Glu Asn Thr Ala Ile Thr Asp Ile His Thr Ala Ala 180

185 190Lys Leu Tyr Gly Tyr Thr Glu Asp Thr Ala Ile Tyr Gly Asp Ala Thr 195 200 205Phe Phe Val Thr Ala Asp Lys Asn Leu Asp Asp Val Met Lys Glu Leu 210 215 220Asn Gly Ile Ser Gly Ile Asn Trp Lys Ser Tyr Thr Leu Val Lys Ser225 230 235 240Ser Ser Asn Tyr Pro Ala Leu Glu Gln Ser Ile Ser Gly Met Tyr Lys 245 250 255Met Ala Asn175694DNAStreptococcus pneumoniaemisc_feature(591)..(591)n is a, c, g, or t 175agtaaatgcg caatcaaatt cattaatatt aatagatgaa cctgaaatct cacttcatcc 60gagtgcaatc tataaattta aagagttttt acttcaagag tgtttaaata aaaaacatca 120aattattatc actacacatt ctacacaact tataaaagat tttcctagag aagccgtgaa 180acttttagtg aaaaacggag aaaaggtaga tgttattgaa aatattgatt atcaggatgc 240attttttgaa ttaggtgatg tgtatcattc taggaagatg atttatgttg aagatagact 300agctaaatat attctagagt ttgttatcac tcattcaggt agtgagaatc ttaaacagaa 360tttagtagtg agatatattc ctggtggagc aaatcaaata atttgtaata atattttaaa 420ctcatcgtat ttagattccg ataaccatta tttttggctt gatggagatc aaaacactaa 480tgttagtgaa tcaaataatt taatgaacta tcttgaaaat ggtgttgtta tatcagataa 540aattcctgaa tcagataata aaaatcttga tgatattata aaattgataa ngggatgtcc 600aattaaattt aatgtttcag gtaataaagg gcaaaaaaat aatattgaat taattgcgaa 660acaaagaagc tttatagatt attgggctaa atac 694176231PRTStreptococcus pneumoniaeSITE(197)..(197)Xaa can be any naturally occurring amino acid 176Val Asn Ala Gln Ser Asn Ser Leu Ile Leu Ile Asp Glu Pro Glu Ile1 5 10 15Ser Leu His Pro Ser Ala Ile Tyr Lys Phe Lys Glu Phe Leu Leu Gln 20 25 30Glu Cys Leu Asn Lys Lys His Gln Ile Ile Ile Thr Thr His Ser Thr 35 40 45Gln Leu Ile Lys Asp Phe Pro Arg Glu Ala Val Lys Leu Leu Val Lys 50 55 60Asn Gly Glu Lys Val Asp Val Ile Glu Asn Ile Asp Tyr Gln Asp Ala65 70 75 80Phe Phe Glu Leu Gly Asp Val Tyr His Ser Arg Lys Met Ile Tyr Val 85 90 95Glu Asp Arg Leu Ala Lys Tyr Ile Leu Glu Phe Val Ile Thr His Ser 100 105 110Gly Ser Glu Asn Leu Lys Gln Asn Leu Val Val Arg Tyr Ile Pro Gly 115 120 125Gly Ala Asn Gln Ile Ile Cys Asn Asn Ile Leu Asn Ser Ser Tyr Leu 130 135 140Asp Ser Asp Asn His Tyr Phe Trp Leu Asp Gly Asp Gln Asn Thr Asn145 150 155 160Val Ser Glu Ser Asn Asn Leu Met Asn Tyr Leu Glu Asn Gly Val Val 165 170 175Ile Ser Asp Lys Ile Pro Glu Ser Asp Asn Lys Asn Leu Asp Asp Ile 180 185 190Ile Lys Leu Ile Xaa Gly Cys Pro Ile Lys Phe Asn Val Ser Gly Asn 195 200 205Lys Gly Gln Lys Asn Asn Ile Glu Leu Ile Ala Lys Gln Arg Ser Phe 210 215 220Ile Asp Tyr Trp Ala Lys Tyr225 230177550DNAStreptococcus pneumoniae 177ttaccgcgtt catcaagatg tcaaacaagt catgacctat caacccatgg tgcgagaaat 60attgagtgaa caagacaccc cagcaaacga agagcttgtg cttgctatga tttatactga 120aacaaaagga aaagaaggcg atgttatgca gtctagtgag tctgcaagtg gttccaccaa 180caccatcaat gataatgcct ctagcattcg gcaaggcatt caaactctga caggcaatct 240ctatctggcg cagaagaagg gggtagatat ctggacagct gttcaagcct ataattttgg 300acctgcctat atcgatttta tcgcccaaaa tggcaaggaa aataccctgg ctctagccaa 360acagtactct cgtgagactg ttgccccctt gcttggtaat aggactggaa agacttatag 420ttatattcac cccatttcca tttttcacgg tgctgaactc tatgtaaatg gaggaaacta 480ttattattct agacaggtac gacttaacct ttacatcatc aaatgtttca ctctcttttc 540aacatctggc 550178183PRTStreptococcus pneumoniae 178Tyr Arg Val His Gln Asp Val Lys Gln Val Met Thr Tyr Gln Pro Met1 5 10 15Val Arg Glu Ile Leu Ser Glu Gln Asp Thr Pro Ala Asn Glu Glu Leu 20 25 30Val Leu Ala Met Ile Tyr Thr Glu Thr Lys Gly Lys Glu Gly Asp Val 35 40 45Met Gln Ser Ser Glu Ser Ala Ser Gly Ser Thr Asn Thr Ile Asn Asp 50 55 60Asn Ala Ser Ser Ile Arg Gln Gly Ile Gln Thr Leu Thr Gly Asn Leu65 70 75 80Tyr Leu Ala Gln Lys Lys Gly Val Asp Ile Trp Thr Ala Val Gln Ala 85 90 95Tyr Asn Phe Gly Pro Ala Tyr Ile Asp Phe Ile Ala Gln Asn Gly Lys 100 105 110Glu Asn Thr Leu Ala Leu Ala Lys Gln Tyr Ser Arg Glu Thr Val Ala 115 120 125Pro Leu Leu Gly Asn Arg Thr Gly Lys Thr Tyr Ser Tyr Ile His Pro 130 135 140Ile Ser Ile Phe His Gly Ala Glu Leu Tyr Val Asn Gly Gly Asn Tyr145 150 155 160Tyr Tyr Ser Arg Gln Val Arg Leu Asn Leu Tyr Ile Ile Lys Cys Phe 165 170 175Thr Leu Phe Ser Thr Ser Gly 180179334DNAStreptococcus pneumoniae 179gtggatgggc tttaactatc ttcgtattcg ccgtgcggct aaaattgtgg acaatgagga 60gtttgaagcc ttgattcgta cgggtcaatt gattgatttg cgcgacccag cagaattcca 120cagaaaacat atccttggtg cacgcaatat tccttcaagt cagttgaaaa ctagtcttgc 180agcccttcgt aaagataaac ctgtccttct ctacgaaaac caacgtgcgc aacgagttac 240aaatgcagct ctttacttga aaaaacaagg tttttctgag atttatatcc tttcttatgg 300cttggattct tggaaaggga aagtgaagac tagc 334180111PRTStreptococcus pneumoniae 180Trp Met Gly Phe Asn Tyr Leu Arg Ile Arg Arg Ala Ala Lys Ile Val1 5 10 15Asp Asn Glu Glu Phe Glu Ala Leu Ile Arg Thr Gly Gln Leu Ile Asp 20 25 30Leu Arg Asp Pro Ala Glu Phe His Arg Lys His Ile Leu Gly Ala Arg 35 40 45Asn Ile Pro Ser Ser Gln Leu Lys Thr Ser Leu Ala Ala Leu Arg Lys 50 55 60Asp Lys Pro Val Leu Leu Tyr Glu Asn Gln Arg Ala Gln Arg Val Thr65 70 75 80Asn Ala Ala Leu Tyr Leu Lys Lys Gln Gly Phe Ser Glu Ile Tyr Ile 85 90 95Leu Ser Tyr Gly Leu Asp Ser Trp Lys Gly Lys Val Lys Thr Ser 100 105 1101811342DNAStreptococcus pneumoniae 181actaaaccag catcgttcgc aggaaaataa ggacaataat cgtgtctctt atgtggatgg 60cagccagtca agtcagaaaa gtgaaaactt gacaccagac caggttagcc agaaagaagg 120aattcaggct gagcaaattg taatcaaaat tacagatcag ggctatgtaa cgtcacacgg 180tgaccactat cattactata atgggaaagt tccttatgat gccctcttta gtgaagaact 240cttgatgaag gatccaaact atcaacttaa agacgctgat attgtcaatg aagtcaaggg 300tggttatatc atcaaggtcg atggaaaata ttatgtctac ctgaaagatg cagctcatgc 360tgataatgtt cgaactaaag atgaaatcaa tcgtcaaaaa caagaacatg tcaaagataa 420tgagaaggtt aactctaatg ttgctgtagc aaggtctcag ggacgatata cgacaaatga 480tggttatgtc tttaatccag ctgatattat cgaagatacg ggtaatgctt atatcgttcc 540tcatggaggt cactatcact acattcccaa aagcgattta tctgctagtg aattagcagc 600agctaaagca catctggctg gaaaaaatat gcaaccgagt cagttaagct attcttcaac 660agctagtgac aataacacgc aatctgtagc aaaaggatca actagcaagc cagcaaataa 720atctgaaaat ctccagagtc ttttgaagga actctatgat tcacctagcg cccaacgtta 780cagtgaatca gatggcctgg tctttgaccc tgctaagatt atcagtcgta caccaaatgg 840agttgcgatt ccgcatggcg accattacca ctttattcct tacagcaagc tttctgcctt 900agaagaaaag attgccagaa tggtgcctat cagtggaact ggttctacag tttctacaaa 960tgcaaaacct aatgaagtag tgtctagtct aggcagtctt tcaagcaatc cttcttcttt 1020aacgacaagt aaggagctct cttcagcatc tgatggttat atttttaatc caaaagatat 1080cgttgaagaa acggctacag cttatattgt aagacatggt gatcatttcc attacattcc 1140aaaatcaaat caaattgggc aaccgactct tccaaacaat agtctagcaa caccttctcc 1200atctcttcca atcaatccag gaacttcaca tgagaaacat gaagaagatg gatacggatt 1260tgatgctaat cgtattatcg ctgaagatga atcaggtttt gtcatgagtc acggagacca 1320caatcattat ttcttcaaga ag 1342182447PRTStreptococcus pneumoniae 182Leu Asn Gln His Arg Ser Gln Glu Asn Lys Asp Asn Asn Arg Val Ser1 5 10 15Tyr Val Asp Gly Ser Gln Ser Ser Gln Lys Ser Glu Asn Leu Thr Pro 20 25 30Asp Gln Val Ser Gln Lys Glu Gly Ile Gln Ala Glu Gln Ile Val Ile 35 40 45Lys Ile Thr Asp Gln Gly Tyr Val Thr Ser His Gly Asp His Tyr His 50 55 60Tyr Tyr Asn Gly Lys Val Pro Tyr Asp Ala Leu Phe Ser Glu Glu Leu65 70 75 80Leu Met Lys Asp Pro Asn Tyr Gln Leu Lys Asp Ala Asp Ile Val Asn 85 90 95Glu Val Lys Gly Gly Tyr Ile Ile Lys Val Asp Gly Lys Tyr Tyr Val 100 105 110Tyr Leu Lys Asp Ala Ala His Ala Asp Asn Val Arg Thr Lys Asp Glu 115 120 125Ile Asn Arg Gln Lys Gln Glu His Val Lys Asp Asn Glu Lys Val Asn 130 135 140Ser Asn Val Ala Val Ala Arg Ser Gln Gly Arg Tyr Thr Thr Asn Asp145 150 155 160Gly Tyr Val Phe Asn Pro Ala Asp Ile Ile Glu Asp Thr Gly Asn Ala 165 170 175Tyr Ile Val Pro His Gly Gly His Tyr His Tyr Ile Pro Lys Ser Asp 180 185 190Leu Ser Ala Ser Glu Leu Ala Ala Ala Lys Ala His Leu Ala Gly Lys 195 200 205Asn Met Gln Pro Ser Gln Leu Ser Tyr Ser Ser Thr Ala Ser Asp Asn 210 215 220Asn Thr Gln Ser Val Ala Lys Gly Ser Thr Ser Lys Pro Ala Asn Lys225 230 235 240Ser Glu Asn Leu Gln Ser Leu Leu Lys Glu Leu Tyr Asp Ser Pro Ser 245 250 255Ala Gln Arg Tyr Ser Glu Ser Asp Gly Leu Val Phe Asp Pro Ala Lys 260 265 270Ile Ile Ser Arg Thr Pro Asn Gly Val Ala Ile Pro His Gly Asp His 275 280 285Tyr His Phe Ile Pro Tyr Ser Lys Leu Ser Ala Leu Glu Glu Lys Ile 290 295 300Ala Arg Met Val Pro Ile Ser Gly Thr Gly Ser Thr Val Ser Thr Asn305 310 315 320Ala Lys Pro Asn Glu Val Val Ser Ser Leu Gly Ser Leu Ser Ser Asn 325 330 335Pro Ser Ser Leu Thr Thr Ser Lys Glu Leu Ser Ser Ala Ser Asp Gly 340 345 350Tyr Ile Phe Asn Pro Lys Asp Ile Val Glu Glu Thr Ala Thr Ala Tyr 355 360 365Ile Val Arg His Gly Asp His Phe His Tyr Ile Pro Lys Ser Asn Gln 370 375 380Ile Gly Gln Pro Thr Leu Pro Asn Asn Ser Leu Ala Thr Pro Ser Pro385 390 395 400Ser Leu Pro Ile Asn Pro Gly Thr Ser His Glu Lys His Glu Glu Asp 405 410 415Gly Tyr Gly Phe Asp Ala Asn Arg Ile Ile Ala Glu Asp Glu Ser Gly 420 425 430Phe Val Met Ser His Gly Asp His Asn His Tyr Phe Phe Lys Lys 435 440 445183934DNAStreptococcus pneumoniae 183tgactacctt gaaatcccac tttacagcta tcttggtgga ttcaacacta aagttcttcc 60aactccaatg atgaacatca tcaacggtgg ttctcactct gacgctccaa tcgctttcca 120agagttcatg atcttgccag ttggtgcgcc aacatttaaa gaagcccttc gttacggtgc 180tgaaatcttc cacgctctta agaaaatcct taaatcacgt ggtttggaaa ctgccgtagg 240tgacgaaggt ggattcgctc ctcgtttcga aggaactgaa gatggtgttg aaactatcct 300tgctgcgatt gaagctgctg gatatgtacc aggtaaagac gtatttatcg gatttgactg 360tgcttcatca gaattctacg ataaagaacg taaagtttac gactacacta aatttgaagg 420tgaaggtgct gctgttcgta catctgcaga acaaatcgac taccttgaag aattggttaa 480caaataccca atcatcacta ttgaagatgg tatggatgaa aacgactggg atggttggaa 540agctcttact gaacgtcttg gtaagaaagt acaacttgtt ggtgacgact tcttcgtaac 600aaacactgac taccttgcac gtggtatcca agaaggtgct gctaactcaa tccttatcaa 660agttaaccaa atcggtactc ttactgaaac ttttgaagct atcgaaatgg ctaaagaagc 720tggttacact gctgttgtat cacaccgttc aggtgaaact gaagattcaa caatcgctga 780tattgcagtt gcaactaacg caggacaaat caagactggt tcactttcac gtacagaccg 840catcgctaaa tacaaccaat tgcttcgtat cgaagaccaa cttggtgaag tagctgaata 900tcgtggattg aaatcattct acaaccttaa aaaa 934184311PRTStreptococcus pneumoniae 184Asp Tyr Leu Glu Ile Pro Leu Tyr Ser Tyr Leu Gly Gly Phe Asn Thr1 5 10 15Lys Val Leu Pro Thr Pro Met Met Asn Ile Ile Asn Gly Gly Ser His 20 25 30Ser Asp Ala Pro Ile Ala Phe Gln Glu Phe Met Ile Leu Pro Val Gly 35 40 45Ala Pro Thr Phe Lys Glu Ala Leu Arg Tyr Gly Ala Glu Ile Phe His 50 55 60Ala Leu Lys Lys Ile Leu Lys Ser Arg Gly Leu Glu Thr Ala Val Gly65 70 75 80Asp Glu Gly Gly Phe Ala Pro Arg Phe Glu Gly Thr Glu Asp Gly Val 85 90 95Glu Thr Ile Leu Ala Ala Ile Glu Ala Ala Gly Tyr Val Pro Gly Lys 100 105 110Asp Val Phe Ile Gly Phe Asp Cys Ala Ser Ser Glu Phe Tyr Asp Lys 115 120 125Glu Arg Lys Val Tyr Asp Tyr Thr Lys Phe Glu Gly Glu Gly Ala Ala 130 135 140Val Arg Thr Ser Ala Glu Gln Ile Asp Tyr Leu Glu Glu Leu Val Asn145 150 155 160Lys Tyr Pro Ile Ile Thr Ile Glu Asp Gly Met Asp Glu Asn Asp Trp 165 170 175Asp Gly Trp Lys Ala Leu Thr Glu Arg Leu Gly Lys Lys Val Gln Leu 180 185 190Val Gly Asp Asp Phe Phe Val Thr Asn Thr Asp Tyr Leu Ala Arg Gly 195 200 205Ile Gln Glu Gly Ala Ala Asn Ser Ile Leu Ile Lys Val Asn Gln Ile 210 215 220Gly Thr Leu Thr Glu Thr Phe Glu Ala Ile Glu Met Ala Lys Glu Ala225 230 235 240Gly Tyr Thr Ala Val Val Ser His Arg Ser Gly Glu Thr Glu Asp Ser 245 250 255Thr Ile Ala Asp Ile Ala Val Ala Thr Asn Ala Gly Gln Ile Lys Thr 260 265 270Gly Ser Leu Ser Arg Thr Asp Arg Ile Ala Lys Tyr Asn Gln Leu Leu 275 280 285Arg Ile Glu Asp Gln Leu Gly Glu Val Ala Glu Tyr Arg Gly Leu Lys 290 295 300Ser Phe Tyr Asn Leu Lys Lys305 310185541DNAStreptococcus pneumoniae 185tcgtatcttt ttttggagca atgttcgcgt agaaggacat tccatggatc cgaccctagc 60ggatggcgaa attctcttcg ttgtaaaaca ccttcctatt gaccgttttg atatcgtggt 120ggcccatgag gaagatggca ataaggacat cgtcaagcgc gtgattggaa tgcctggcga 180caccattcgt tacgaaaatg ataaactcta catcaatgac aaagaaacgg acgagcctta 240tctagcagac tatatcaaac gcttcaagga tgacaaactc caaagcactt actcaggcaa 300gggctttgaa ggaaataaag gaactttctt tagaagtatc gctcaaaaag ctcaagcctt 360cacagttgat gtcaactaca acaccaactt tagctttact gttccagaag gagaatacct 420tctcctcgga gatgaccgct tggtttcgag cgacagccgc cacgtaggta ccttcaaagc 480aaaagatatc acaggggaag ctaaattccg cttatggcca atcacccgta tcggaacatt 540t 541186180PRTStreptococcus pneumoniae 186Arg Ile Phe Phe Trp Ser Asn Val Arg Val Glu Gly His Ser Met Asp1 5 10 15Pro Thr Leu Ala Asp Gly Glu Ile Leu Phe Val Val Lys His Leu Pro 20 25 30Ile Asp Arg Phe Asp Ile Val Val Ala His Glu Glu Asp Gly Asn Lys 35 40 45Asp Ile Val Lys Arg Val Ile Gly Met Pro Gly Asp Thr Ile Arg Tyr 50 55 60Glu Asn Asp Lys Leu Tyr Ile Asn Asp Lys Glu Thr Asp Glu Pro Tyr65 70 75 80Leu Ala Asp Tyr Ile Lys Arg Phe Lys Asp Asp Lys Leu Gln Ser Thr 85 90 95Tyr Ser Gly Lys Gly Phe Glu Gly Asn Lys Gly Thr Phe Phe Arg Ser 100 105 110Ile Ala Gln Lys Ala Gln Ala Phe Thr Val Asp Val Asn Tyr Asn Thr 115 120 125Asn Phe Ser Phe Thr Val Pro Glu Gly Glu Tyr Leu Leu Leu Gly Asp 130 135 140Asp Arg Leu Val Ser Ser Asp Ser Arg His Val Gly Thr Phe Lys Ala145 150 155 160Lys Asp Ile Thr Gly Glu Ala Lys Phe Arg Leu Trp Pro Ile Thr Arg 165 170 175Ile Gly Thr Phe 180187400DNAStreptococcus pneumoniae 187ggactctctc aaagatgtga aagcaaatgc tagcgacagc aagcctgcac aggacaagaa 60ggatgcaaaa caaggaacgg aagatagtaa ggattcagat aagatgactg aaacaaactc 120agttccggca ggagtgattg tggtcagtct acttgccctc ctaggcgtga ttgccttctg 180gctgattcgc cgtaagaaag agtcagaaat ccagcaatta agcacggaat tgatcaaggt 240tctaggacag ctagatgcag aaaaagcgga taaaaaagtc cttgccaaag cccaaaacct 300tctccaagaa acccttgatt tcgtgaaaga agaaaatggc tcagcagaga cagaaactaa 360actagtagag gagcttaaag caatccttga caaactcaag 400188133PRTStreptococcus pneumoniae 188Asp Ser Leu Lys Asp Val Lys Ala Asn Ala Ser Asp Ser Lys Pro Ala1 5 10 15Gln Asp Lys Lys Asp Ala Lys Gln Gly Thr Glu Asp Ser Lys Asp Ser 20

25 30Asp Lys Met Thr Glu Thr Asn Ser Val Pro Ala Gly Val Ile Val Val 35 40 45Ser Leu Leu Ala Leu Leu Gly Val Ile Ala Phe Trp Leu Ile Arg Arg 50 55 60Lys Lys Glu Ser Glu Ile Gln Gln Leu Ser Thr Glu Leu Ile Lys Val65 70 75 80Leu Gly Gln Leu Asp Ala Glu Lys Ala Asp Lys Lys Val Leu Ala Lys 85 90 95Ala Gln Asn Leu Leu Gln Glu Thr Leu Asp Phe Val Lys Glu Glu Asn 100 105 110Gly Ser Ala Glu Thr Glu Thr Lys Leu Val Glu Glu Leu Lys Ala Ile 115 120 125Leu Asp Lys Leu Lys 1301891201DNAStreptococcus pneumoniae 189caagaaatcc tatcatctct tccagaagca aacagagacg aggggaattc agactcagtt 60gattgaagaa tcgcttagtc agcagactat aatccagtcc ttcaatgctc aaacagaatt 120tatccaaaga ttgcgtgagg ctcatgacaa ctactcaggc tattctcagt cagccatctt 180ttattcttca acggtcaatc cttcgactcg ctttgtaaat gcactcattt atgccctttt 240agctggagta ggagcttatc gtatcatgat gggttcagcc ttgaccgtcg gtcgtttagt 300gacttttttg aactatgttc agcaatacac caagcccttt aacgatattt cttcagtgct 360agctgagttg caaagtgctc tggcttgcgt agagcgtatc tatggagtct tagatagccc 420tgaagtggct gaaacaggta aggaagtctt gacgaccagt gaccaagtta agggagctat 480ttcctttaaa catgtctctt ttggctacca tcctgaaaaa attttgatta aggacttgtc 540tatcgatatt ccagctggta gtaaggtagc catcgttggt ccgacaggtg ctggaaaatc 600aactcttatc aatctcctta tgcgttttta tcccattagc tcgggagata tcttgctgga 660tgggcaatcc atttatgatt atacacgagt atcattgaga cagcagtttg gtatggtgct 720tcaagaaacc tggctcacac aagggaccat tcatgataat attgcctttg gcaatcctga 780agccagtcga gagcaagtaa ttgctgctgc caaagcagct aatgcagact ttttcatcca 840acagttgcca cagggatacg ataccaagtt ggaaaatgct ggagaatctc tctctgtcgg 900ccaagctcag ctcttgacca tagcccgagt ctttctggct attccaaaga ttcttatctt 960agacgaggca acttcttcca ttgatacacg gacagaagtg ctggtacagg atgcctttgc 1020aaaactcatg aagggccgca caagtttcat cattgctcac cgtttgtcaa ccattcagga 1080tgcggattta attcttgtct tagtagatgg tgatattgtt gaatatggta accatcaaga 1140actcatggat agaaagggta agtattacca aatgcaaaaa gctgcggctt ttagttctga 1200a 1201190400PRTStreptococcus pneumoniae 190Lys Lys Ser Tyr His Leu Phe Gln Lys Gln Thr Glu Thr Arg Gly Ile1 5 10 15Gln Thr Gln Leu Ile Glu Glu Ser Leu Ser Gln Gln Thr Ile Ile Gln 20 25 30Ser Phe Asn Ala Gln Thr Glu Phe Ile Gln Arg Leu Arg Glu Ala His 35 40 45Asp Asn Tyr Ser Gly Tyr Ser Gln Ser Ala Ile Phe Tyr Ser Ser Thr 50 55 60Val Asn Pro Ser Thr Arg Phe Val Asn Ala Leu Ile Tyr Ala Leu Leu65 70 75 80Ala Gly Val Gly Ala Tyr Arg Ile Met Met Gly Ser Ala Leu Thr Val 85 90 95Gly Arg Leu Val Thr Phe Leu Asn Tyr Val Gln Gln Tyr Thr Lys Pro 100 105 110Phe Asn Asp Ile Ser Ser Val Leu Ala Glu Leu Gln Ser Ala Leu Ala 115 120 125Cys Val Glu Arg Ile Tyr Gly Val Leu Asp Ser Pro Glu Val Ala Glu 130 135 140Thr Gly Lys Glu Val Leu Thr Thr Ser Asp Gln Val Lys Gly Ala Ile145 150 155 160Ser Phe Lys His Val Ser Phe Gly Tyr His Pro Glu Lys Ile Leu Ile 165 170 175Lys Asp Leu Ser Ile Asp Ile Pro Ala Gly Ser Lys Val Ala Ile Val 180 185 190Gly Pro Thr Gly Ala Gly Lys Ser Thr Leu Ile Asn Leu Leu Met Arg 195 200 205Phe Tyr Pro Ile Ser Ser Gly Asp Ile Leu Leu Asp Gly Gln Ser Ile 210 215 220Tyr Asp Tyr Thr Arg Val Ser Leu Arg Gln Gln Phe Gly Met Val Leu225 230 235 240Gln Glu Thr Trp Leu Thr Gln Gly Thr Ile His Asp Asn Ile Ala Phe 245 250 255Gly Asn Pro Glu Ala Ser Arg Glu Gln Val Ile Ala Ala Ala Lys Ala 260 265 270Ala Asn Ala Asp Phe Phe Ile Gln Gln Leu Pro Gln Gly Tyr Asp Thr 275 280 285Lys Leu Glu Asn Ala Gly Glu Ser Leu Ser Val Gly Gln Ala Gln Leu 290 295 300Leu Thr Ile Ala Arg Val Phe Leu Ala Ile Pro Lys Ile Leu Ile Leu305 310 315 320Asp Glu Ala Thr Ser Ser Ile Asp Thr Arg Thr Glu Val Leu Val Gln 325 330 335Asp Ala Phe Ala Lys Leu Met Lys Gly Arg Thr Ser Phe Ile Ile Ala 340 345 350His Arg Leu Ser Thr Ile Gln Asp Ala Asp Leu Ile Leu Val Leu Val 355 360 365Asp Gly Asp Ile Val Glu Tyr Gly Asn His Gln Glu Leu Met Asp Arg 370 375 380Lys Gly Lys Tyr Tyr Gln Met Gln Lys Ala Ala Ala Phe Ser Ser Glu385 390 395 4001911033DNAStreptococcus pneumoniae 191acgaaatgca gggcagacag atgcctcgca aattgaaaag gcggcagtta gccaaggagg 60aaaagcagtg aaaaaaacag aaattagtaa agacgcagac ttgcacgaaa tttatctagc 120tggaggttgt ttctggggag tggaggaata tttctcacgt gttcccgggg tgacggatgc 180cgtttcaggc tatgcaaatg gtagaggaga aacaaccaag tacgaattga ttaaccaaac 240aggtcatgca gaaaccgtcc atgtcaccta tgatgccaag caaatttctc tcaaggaaat 300cctgcttcac tatttccgca ttatcaatcc aaccagcaaa aataaacaag gaaatgatgt 360ggggacccag taccgtactg gtgtttatta cacagatgac aaggatttgg aagtgattaa 420ccaagtcttt gatgaggtgg ctaagaaata cgatcaacct ctagcagttg aaaaggaaaa 480cttgaagaat tttgtggtgg ctgaggatta ccatcaagac tatctcaaga aaaatccaaa 540tggctactgc catatcaatg ttaatcaggc ggcctatcct gtcattgatg ccagcaaata 600tccaaaacca agtgatgagg aattgaaaaa gaccctgtca cctgaggagt atgcagttac 660ccaggaaaat caaacagaac gagctttctc aaaccgttac tgggataaat ttgaatccgg 720tatctatgtg gatatagcaa ctggggaacc tctcttttca tcaaaagaca aatttgagtc 780tggttgtggc tggcctagtt ttacccaacc catcagtcca gatgttgtca cctacaagga 840agataagtcc tacaatatga cgcgtatgga agtgcggagc cgagtaggag attctcacct 900tgggcatgtc tttacggatg gtccacagga caagggcggc ttacgttact gtatcaatag 960cctctctatc cgctttattc ccaaagacca aatggaagaa aaaggctacg cttatttact 1020agattatgtt gat 1033192344PRTStreptococcus pneumoniae 192Arg Asn Ala Gly Gln Thr Asp Ala Ser Gln Ile Glu Lys Ala Ala Val1 5 10 15Ser Gln Gly Gly Lys Ala Val Lys Lys Thr Glu Ile Ser Lys Asp Ala 20 25 30Asp Leu His Glu Ile Tyr Leu Ala Gly Gly Cys Phe Trp Gly Val Glu 35 40 45Glu Tyr Phe Ser Arg Val Pro Gly Val Thr Asp Ala Val Ser Gly Tyr 50 55 60Ala Asn Gly Arg Gly Glu Thr Thr Lys Tyr Glu Leu Ile Asn Gln Thr65 70 75 80Gly His Ala Glu Thr Val His Val Thr Tyr Asp Ala Lys Gln Ile Ser 85 90 95Leu Lys Glu Ile Leu Leu His Tyr Phe Arg Ile Ile Asn Pro Thr Ser 100 105 110Lys Asn Lys Gln Gly Asn Asp Val Gly Thr Gln Tyr Arg Thr Gly Val 115 120 125Tyr Tyr Thr Asp Asp Lys Asp Leu Glu Val Ile Asn Gln Val Phe Asp 130 135 140Glu Val Ala Lys Lys Tyr Asp Gln Pro Leu Ala Val Glu Lys Glu Asn145 150 155 160Leu Lys Asn Phe Val Val Ala Glu Asp Tyr His Gln Asp Tyr Leu Lys 165 170 175Lys Asn Pro Asn Gly Tyr Cys His Ile Asn Val Asn Gln Ala Ala Tyr 180 185 190Pro Val Ile Asp Ala Ser Lys Tyr Pro Lys Pro Ser Asp Glu Glu Leu 195 200 205Lys Lys Thr Leu Ser Pro Glu Glu Tyr Ala Val Thr Gln Glu Asn Gln 210 215 220Thr Glu Arg Ala Phe Ser Asn Arg Tyr Trp Asp Lys Phe Glu Ser Gly225 230 235 240Ile Tyr Val Asp Ile Ala Thr Gly Glu Pro Leu Phe Ser Ser Lys Asp 245 250 255Lys Phe Glu Ser Gly Cys Gly Trp Pro Ser Phe Thr Gln Pro Ile Ser 260 265 270Pro Asp Val Val Thr Tyr Lys Glu Asp Lys Ser Tyr Asn Met Thr Arg 275 280 285Met Glu Val Arg Ser Arg Val Gly Asp Ser His Leu Gly His Val Phe 290 295 300Thr Asp Gly Pro Gln Asp Lys Gly Gly Leu Arg Tyr Cys Ile Asn Ser305 310 315 320Leu Ser Ile Arg Phe Ile Pro Lys Asp Gln Met Glu Glu Lys Gly Tyr 325 330 335Ala Tyr Leu Leu Asp Tyr Val Asp 340193396DNAStreptococcus pneumoniaemisc_feature(35)..(35)n is a, c, g, or t 193tgtatagttt ttagcgcttg ttcttctaat tctgntaaaa atgaagaaaa tacttctaaa 60gagcatgcgc ctgataaaat agttttagat catgctttcg gtcaaactat attagataaa 120aaacctgaaa gagttgcaac tattgcttgg ggaaatcatg atgtagcatt agctttagga 180atagttcctg ttggattttc aaaagcaaat tacggtgtaa gtgctgataa aggagtttta 240ccatggacag aagaaaaaat caaagaacta aatggtaaag ctaacctatt tgacgatttg 300gatggactta actttgaagc aatatcaaat tctaaaccag atgttatctt agcaggttat 360tctggtataa ctaaagaaga ttatgacact ctatca 396194132PRTStreptococcus pneumoniaeSITE(12)..(12)Xaa can be any naturally occurring amino acid 194Cys Ile Val Phe Ser Ala Cys Ser Ser Asn Ser Xaa Lys Asn Glu Glu1 5 10 15Asn Thr Ser Lys Glu His Ala Pro Asp Lys Ile Val Leu Asp His Ala 20 25 30Phe Gly Gln Thr Ile Leu Asp Lys Lys Pro Glu Arg Val Ala Thr Ile 35 40 45Ala Trp Gly Asn His Asp Val Ala Leu Ala Leu Gly Ile Val Pro Val 50 55 60Gly Phe Ser Lys Ala Asn Tyr Gly Val Ser Ala Asp Lys Gly Val Leu65 70 75 80Pro Trp Thr Glu Glu Lys Ile Lys Glu Leu Asn Gly Lys Ala Asn Leu 85 90 95Phe Asp Asp Leu Asp Gly Leu Asn Phe Glu Ala Ile Ser Asn Ser Lys 100 105 110Pro Asp Val Ile Leu Ala Gly Tyr Ser Gly Ile Thr Lys Glu Asp Tyr 115 120 125Asp Thr Leu Ser 130195844DNAStreptococcus pneumoniae 195gtgtgtcgag catattctga agcaaaccta tcaaaatata gaaattattt tagttgatga 60cggttctacg gataattctg gggaaatttg tgatgctttt atgatgcaag ataatcgtgt 120gcgagtattg catcaagaaa ataagggggg ggcagcacaa gctaaaaata tggggattag 180tgtagctaag ggagagtaca tcacgattgt tgattcagat gatatcgtaa aagaaaatat 240gattgaaact ctttatcagc aagtccaaga aaaggatgca gatgttgtta tagggaatta 300ctataattat gacgaaagtg acgggaattt ttatttttat gtaacagggc aagatttttg 360cgtcgaagaa ttagctatac aagaaattat gaaccgtcaa gcaggagatt ggaaattcaa 420tagctcggcc tttatattgc cgacatttaa gttgattaaa aaagaattat tcaatgaagt 480tcacttttca aatggtcgcc gctttgatga tgaagcaact atgcatcgct tttatctttt 540agcctctaaa atcgtcttta taaacgataa tctctatctg tatagaagac gttcaggaag 600catcatgaga acggaatttg atctttcctg ggcaagagat attgttgaag tgttttctaa 660gaaaatatcg gattgtgtct tggctggttt ggatgtctcc gttctgcgta ttcgatttgt 720caatctttta aaagattata agcaaacttt agaataccat caattaacag atactgagga 780atataaagat atttgtttca gattaaagtt gttttttgat gcagaacaaa gaaatggtaa 840aagt 844196281PRTStreptococcus pneumoniae 196Cys Val Glu His Ile Leu Lys Gln Thr Tyr Gln Asn Ile Glu Ile Ile1 5 10 15Leu Val Asp Asp Gly Ser Thr Asp Asn Ser Gly Glu Ile Cys Asp Ala 20 25 30Phe Met Met Gln Asp Asn Arg Val Arg Val Leu His Gln Glu Asn Lys 35 40 45Gly Gly Ala Ala Gln Ala Lys Asn Met Gly Ile Ser Val Ala Lys Gly 50 55 60Glu Tyr Ile Thr Ile Val Asp Ser Asp Asp Ile Val Lys Glu Asn Met65 70 75 80Ile Glu Thr Leu Tyr Gln Gln Val Gln Glu Lys Asp Ala Asp Val Val 85 90 95Ile Gly Asn Tyr Tyr Asn Tyr Asp Glu Ser Asp Gly Asn Phe Tyr Phe 100 105 110Tyr Val Thr Gly Gln Asp Phe Cys Val Glu Glu Leu Ala Ile Gln Glu 115 120 125Ile Met Asn Arg Gln Ala Gly Asp Trp Lys Phe Asn Ser Ser Ala Phe 130 135 140Ile Leu Pro Thr Phe Lys Leu Ile Lys Lys Glu Leu Phe Asn Glu Val145 150 155 160His Phe Ser Asn Gly Arg Arg Phe Asp Asp Glu Ala Thr Met His Arg 165 170 175Phe Tyr Leu Leu Ala Ser Lys Ile Val Phe Ile Asn Asp Asn Leu Tyr 180 185 190Leu Tyr Arg Arg Arg Ser Gly Ser Ile Met Arg Thr Glu Phe Asp Leu 195 200 205Ser Trp Ala Arg Asp Ile Val Glu Val Phe Ser Lys Lys Ile Ser Asp 210 215 220Cys Val Leu Ala Gly Leu Asp Val Ser Val Leu Arg Ile Arg Phe Val225 230 235 240Asn Leu Leu Lys Asp Tyr Lys Gln Thr Leu Glu Tyr His Gln Leu Thr 245 250 255Asp Thr Glu Glu Tyr Lys Asp Ile Cys Phe Arg Leu Lys Leu Phe Phe 260 265 270Asp Ala Glu Gln Arg Asn Gly Lys Ser 275 280197811DNAStreptococcus pneumoniae 197gtgtttggat agcattcaga atcagacgta tcaaaatttt gagtgtttat taatcaatga 60tggctctcca gatcattcat ccaaaatatg tgaagaattt gtagagaaag attctcgttt 120caaatatttt gagaaagcaa acggcggtct ttcatcagct cgtaacctag gtattgaatg 180ttcggggggg gcgtacatta cttttgtaga ctctgatgat tggttggaac atgatgcttt 240agaccgatta tatggtgctt tgaaaaagga aaacgcagat attagtatcg ggcgttataa 300ttcttatgat gaaacacgct atgtgtatat gacttatgtt acggatccag atgattctct 360agaagtgata gaaggtaaag caattatgga tagggaaggt gtcgaagaag tcagaaatgg 420gaactggact gtagctgtct tgaagttatt caagagagag ttactacaag atttaccatt 480tcctatagga aaaattgcag aggatactta ctggacatgg aaggtacttc taagagcttc 540gaggatagtc tatttgaatc gttgtgttta ctggtaccgt gttggtttat ctgatacttt 600atcgaataca tggagtgaaa agcgtatgta tgatgaaatt ggggctaggg aagaaaagat 660agctatttta gcaagttcag actatgactt gaccaatcat attttgattt ataaaaatag 720attacaaaga gtgatagcaa aattagaaga acaaaatatg cagttcacag agatttacag 780aagaatgatg gaaaaattgt ctttacttcc g 811198270PRTStreptococcus pneumoniae 198Cys Leu Asp Ser Ile Gln Asn Gln Thr Tyr Gln Asn Phe Glu Cys Leu1 5 10 15Leu Ile Asn Asp Gly Ser Pro Asp His Ser Ser Lys Ile Cys Glu Glu 20 25 30Phe Val Glu Lys Asp Ser Arg Phe Lys Tyr Phe Glu Lys Ala Asn Gly 35 40 45Gly Leu Ser Ser Ala Arg Asn Leu Gly Ile Glu Cys Ser Gly Gly Ala 50 55 60Tyr Ile Thr Phe Val Asp Ser Asp Asp Trp Leu Glu His Asp Ala Leu65 70 75 80Asp Arg Leu Tyr Gly Ala Leu Lys Lys Glu Asn Ala Asp Ile Ser Ile 85 90 95Gly Arg Tyr Asn Ser Tyr Asp Glu Thr Arg Tyr Val Tyr Met Thr Tyr 100 105 110Val Thr Asp Pro Asp Asp Ser Leu Glu Val Ile Glu Gly Lys Ala Ile 115 120 125Met Asp Arg Glu Gly Val Glu Glu Val Arg Asn Gly Asn Trp Thr Val 130 135 140Ala Val Leu Lys Leu Phe Lys Arg Glu Leu Leu Gln Asp Leu Pro Phe145 150 155 160Pro Ile Gly Lys Ile Ala Glu Asp Thr Tyr Trp Thr Trp Lys Val Leu 165 170 175Leu Arg Ala Ser Arg Ile Val Tyr Leu Asn Arg Cys Val Tyr Trp Tyr 180 185 190Arg Val Gly Leu Ser Asp Thr Leu Ser Asn Thr Trp Ser Glu Lys Arg 195 200 205Met Tyr Asp Glu Ile Gly Ala Arg Glu Glu Lys Ile Ala Ile Leu Ala 210 215 220Ser Ser Asp Tyr Asp Leu Thr Asn His Ile Leu Ile Tyr Lys Asn Arg225 230 235 240Leu Gln Arg Val Ile Ala Lys Leu Glu Glu Gln Asn Met Gln Phe Thr 245 250 255Glu Ile Tyr Arg Arg Met Met Glu Lys Leu Ser Leu Leu Pro 260 265 2701992023DNAStreptococcus pneumoniae 199gtgcctagat agtattatta ctcaaacata taaaaatatt gagattgttg tcgttaatga 60tggttctacg gatgcttcag gtgaaatttg taaagaattt tcagaaatgg atcaccgaat 120tctctatata gaacaagaaa atgctggtct ttctgccgca cgaaacaccg gtctgaataa 180tatgtccgga aattatgtga cctttgtgga ctcggatgat tggattgagc aagattatgt 240agaaactcta tataaaaaaa tagtagagta tcaggctgat attgcagttg gtaattatta 300ttctttcaac gaaagtgaag gaatgttcta ctttcatata ttgggagact cctattatga 360gaaagtatat gataatgttt ctatctttga gaacttgtat gaaactcaag aaatgaagag 420ttttgctttg atatctgctt ggggtaaact ctataaggca agattgtttg agcagttgcg 480ctttgacata ggtaaattag gagaagatgg ttacctcaat caaaaggtat atttattatc 540agaaaaggta atttatttaa ataaaagtct ttatgcttat cggattagaa aaggtagttt 600atcaagagtt tggacagaaa agtggatgca cgctttagtt gatgctatgt ctgaacgtat 660tacgctacta gctaatatgg gttatcctct agagaaacac ttggcagttt atcgtcagat 720gttggaagtc agtctcgcca acggtcaagc tagtggttta tctgacacag caacgtataa 780agagtttgaa atgaaacaaa ggcttttaaa

tcagctatcg agacaagagg aaagtgaaaa 840gaaagccatt gtcctcgcag caaactatgg ctatgtagac caagttttaa cgacaatcaa 900gtctatttgt tatcataatc gttcgattcg tttttatctg attcatagcg attttccaaa 960tgaatggatt aagcaattaa ataagcgctt agagaagttt gactcagaaa ttattaattg 1020tcgggtaact tctgagcaaa tttcatgtta taaatcggat attagttaca cagtcttttt 1080acgctatttc atagctgatt tcgtgcaaga agacaaggcc ctctacttgg actgtgatct 1140agttgtaacg aaaaatctgg atgacttgtt tgctacagac ttacaagatt atcctttggc 1200tgctgttaga gattttgggg gcagagctta ttttggtcaa gaaatcttta atgccggtgt 1260tctcttggta aacaatgctt tttggaaaaa agagaatatg acccaaaaat taattgatgt 1320aaccaatgaa tggcatgata aggtggatca ggcagatcag agcatcttga atatgctttt 1380tgaacataaa tggttggaat tggactttga ttataatcat attgtcattc ataaacagtt 1440tgctgattat caattgcctg agggtcagga ttatcctgct attattcact atctttctca 1500tcggaaaccg tggaaagatt tggcggccca aacctatcgt gaagtttggt ggtactatca 1560tgggcttgaa tggacagaat tgggacaaaa ccatcattta catccattac aaagatctca 1620catctatcca ataaaggaac ctttcacttg tctaatctat actgcctcag accatattga 1680acaaattgag acattggttc aatccttgcc tgatattcag tttaagatag cagctagagt 1740aatagttagt gatcgattgg ctcagatgac aatttatcca aacgtgacta tatttaacgg 1800aattcactat ttggtagatg tcgataatga attggtagaa accagtcaag tacttttaga 1860tattaatcat ggcgaaaaga cagaagaaat tctcgatcaa tttgctaatc ttggcaagcc 1920tatcttatcc tttgaaaata ctaaaaccta tgaagtaggt caggaggcat atgctgttga 1980ccaagttcaa gcaatgattg aaaaattgag agaaataagc aaa 2023200674PRTStreptococcus pneumoniae 200Cys Leu Asp Ser Ile Ile Thr Gln Thr Tyr Lys Asn Ile Glu Ile Val1 5 10 15Val Val Asn Asp Gly Ser Thr Asp Ala Ser Gly Glu Ile Cys Lys Glu 20 25 30Phe Ser Glu Met Asp His Arg Ile Leu Tyr Ile Glu Gln Glu Asn Ala 35 40 45Gly Leu Ser Ala Ala Arg Asn Thr Gly Leu Asn Asn Met Ser Gly Asn 50 55 60Tyr Val Thr Phe Val Asp Ser Asp Asp Trp Ile Glu Gln Asp Tyr Val65 70 75 80Glu Thr Leu Tyr Lys Lys Ile Val Glu Tyr Gln Ala Asp Ile Ala Val 85 90 95Gly Asn Tyr Tyr Ser Phe Asn Glu Ser Glu Gly Met Phe Tyr Phe His 100 105 110Ile Leu Gly Asp Ser Tyr Tyr Glu Lys Val Tyr Asp Asn Val Ser Ile 115 120 125Phe Glu Asn Leu Tyr Glu Thr Gln Glu Met Lys Ser Phe Ala Leu Ile 130 135 140Ser Ala Trp Gly Lys Leu Tyr Lys Ala Arg Leu Phe Glu Gln Leu Arg145 150 155 160Phe Asp Ile Gly Lys Leu Gly Glu Asp Gly Tyr Leu Asn Gln Lys Val 165 170 175Tyr Leu Leu Ser Glu Lys Val Ile Tyr Leu Asn Lys Ser Leu Tyr Ala 180 185 190Tyr Arg Ile Arg Lys Gly Ser Leu Ser Arg Val Trp Thr Glu Lys Trp 195 200 205Met His Ala Leu Val Asp Ala Met Ser Glu Arg Ile Thr Leu Leu Ala 210 215 220Asn Met Gly Tyr Pro Leu Glu Lys His Leu Ala Val Tyr Arg Gln Met225 230 235 240Leu Glu Val Ser Leu Ala Asn Gly Gln Ala Ser Gly Leu Ser Asp Thr 245 250 255Ala Thr Tyr Lys Glu Phe Glu Met Lys Gln Arg Leu Leu Asn Gln Leu 260 265 270Ser Arg Gln Glu Glu Ser Glu Lys Lys Ala Ile Val Leu Ala Ala Asn 275 280 285Tyr Gly Tyr Val Asp Gln Val Leu Thr Thr Ile Lys Ser Ile Cys Tyr 290 295 300His Asn Arg Ser Ile Arg Phe Tyr Leu Ile His Ser Asp Phe Pro Asn305 310 315 320Glu Trp Ile Lys Gln Leu Asn Lys Arg Leu Glu Lys Phe Asp Ser Glu 325 330 335Ile Ile Asn Cys Arg Val Thr Ser Glu Gln Ile Ser Cys Tyr Lys Ser 340 345 350Asp Ile Ser Tyr Thr Val Phe Leu Arg Tyr Phe Ile Ala Asp Phe Val 355 360 365Gln Glu Asp Lys Ala Leu Tyr Leu Asp Cys Asp Leu Val Val Thr Lys 370 375 380Asn Leu Asp Asp Leu Phe Ala Thr Asp Leu Gln Asp Tyr Pro Leu Ala385 390 395 400Ala Val Arg Asp Phe Gly Gly Arg Ala Tyr Phe Gly Gln Glu Ile Phe 405 410 415Asn Ala Gly Val Leu Leu Val Asn Asn Ala Phe Trp Lys Lys Glu Asn 420 425 430Met Thr Gln Lys Leu Ile Asp Val Thr Asn Glu Trp His Asp Lys Val 435 440 445Asp Gln Ala Asp Gln Ser Ile Leu Asn Met Leu Phe Glu His Lys Trp 450 455 460Leu Glu Leu Asp Phe Asp Tyr Asn His Ile Val Ile His Lys Gln Phe465 470 475 480Ala Asp Tyr Gln Leu Pro Glu Gly Gln Asp Tyr Pro Ala Ile Ile His 485 490 495Tyr Leu Ser His Arg Lys Pro Trp Lys Asp Leu Ala Ala Gln Thr Tyr 500 505 510Arg Glu Val Trp Trp Tyr Tyr His Gly Leu Glu Trp Thr Glu Leu Gly 515 520 525Gln Asn His His Leu His Pro Leu Gln Arg Ser His Ile Tyr Pro Ile 530 535 540Lys Glu Pro Phe Thr Cys Leu Ile Tyr Thr Ala Ser Asp His Ile Glu545 550 555 560Gln Ile Glu Thr Leu Val Gln Ser Leu Pro Asp Ile Gln Phe Lys Ile 565 570 575Ala Ala Arg Val Ile Val Ser Asp Arg Leu Ala Gln Met Thr Ile Tyr 580 585 590Pro Asn Val Thr Ile Phe Asn Gly Ile His Tyr Leu Val Asp Val Asp 595 600 605Asn Glu Leu Val Glu Thr Ser Gln Val Leu Leu Asp Ile Asn His Gly 610 615 620Glu Lys Thr Glu Glu Ile Leu Asp Gln Phe Ala Asn Leu Gly Lys Pro625 630 635 640Ile Leu Ser Phe Glu Asn Thr Lys Thr Tyr Glu Val Gly Gln Glu Ala 645 650 655Tyr Ala Val Asp Gln Val Gln Ala Met Ile Glu Lys Leu Arg Glu Ile 660 665 670Ser Lys201910DNAStreptococcus pneumoniae 201cattcagaag cagacctatc aaaatctgga aattattctt gttgatgatg gtgcaacaga 60tgaaagtggt cgcttgtgtg attcaatcgc tgaacaagat gacagggtgt cagtgcttca 120taaaaagaac gaaggattgt cgcaagcacg aaatgatggg atgaagcagg ctcacgggga 180ttatctgatt tttattgact cagatgatta tatccatcca gaaatgattc agagcttata 240tgagcaatta gttcaagaag atgcggatgt ttcgagctgt ggtgtcatga atgtctatgc 300taatgatgaa agcccacagt cagccaatca ggatgactat tttgtctgtg attctcaaac 360atttctaaag gaatacctca taggtgaaaa aatacctggg acgatttgca ataagctaat 420caagagacag attgcaactg ccctatcctt tcctaagggg ttgatttacg aagatgccta 480ttaccatttt gatttaatca agttggccaa gaagtatgtg gttaatacta aaccctatta 540ttactatttc catagagggg atagtattac gaccaaaccc tatgcagaga aggatttagc 600ctatattgat atctaccaaa agttttataa tgaagttgtg aaaaactatc ctgacttgaa 660agaggtcgct tttttcagat tggcctatgc ccacttcttt attctggata agatgttgct 720agatgatcag tataaacagt ttgaagccta ttctcagatt catcgttttt taaaaggcca 780tgcctttgct atttctagga atccaatttt ccgtaagggg agaagaatta gtgctttggc 840cctattcata aatatttcct tatatcgatt cttattactg aaaaatattg aaaaatctaa 900aaaattacat 910202303PRTStreptococcus pneumoniae 202Ile Gln Lys Gln Thr Tyr Gln Asn Leu Glu Ile Ile Leu Val Asp Asp1 5 10 15Gly Ala Thr Asp Glu Ser Gly Arg Leu Cys Asp Ser Ile Ala Glu Gln 20 25 30Asp Asp Arg Val Ser Val Leu His Lys Lys Asn Glu Gly Leu Ser Gln 35 40 45Ala Arg Asn Asp Gly Met Lys Gln Ala His Gly Asp Tyr Leu Ile Phe 50 55 60Ile Asp Ser Asp Asp Tyr Ile His Pro Glu Met Ile Gln Ser Leu Tyr65 70 75 80Glu Gln Leu Val Gln Glu Asp Ala Asp Val Ser Ser Cys Gly Val Met 85 90 95Asn Val Tyr Ala Asn Asp Glu Ser Pro Gln Ser Ala Asn Gln Asp Asp 100 105 110Tyr Phe Val Cys Asp Ser Gln Thr Phe Leu Lys Glu Tyr Leu Ile Gly 115 120 125Glu Lys Ile Pro Gly Thr Ile Cys Asn Lys Leu Ile Lys Arg Gln Ile 130 135 140Ala Thr Ala Leu Ser Phe Pro Lys Gly Leu Ile Tyr Glu Asp Ala Tyr145 150 155 160Tyr His Phe Asp Leu Ile Lys Leu Ala Lys Lys Tyr Val Val Asn Thr 165 170 175Lys Pro Tyr Tyr Tyr Tyr Phe His Arg Gly Asp Ser Ile Thr Thr Lys 180 185 190Pro Tyr Ala Glu Lys Asp Leu Ala Tyr Ile Asp Ile Tyr Gln Lys Phe 195 200 205Tyr Asn Glu Val Val Lys Asn Tyr Pro Asp Leu Lys Glu Val Ala Phe 210 215 220Phe Arg Leu Ala Tyr Ala His Phe Phe Ile Leu Asp Lys Met Leu Leu225 230 235 240Asp Asp Gln Tyr Lys Gln Phe Glu Ala Tyr Ser Gln Ile His Arg Phe 245 250 255Leu Lys Gly His Ala Phe Ala Ile Ser Arg Asn Pro Ile Phe Arg Lys 260 265 270Gly Arg Arg Ile Ser Ala Leu Ala Leu Phe Ile Asn Ile Ser Leu Tyr 275 280 285Arg Phe Leu Leu Leu Lys Asn Ile Glu Lys Ser Lys Lys Leu His 290 295 3002031972DNAStreptococcus pneumoniae 203taaggctgat aatcgtgttc aaatgagaac gacgattaat aatgaatcgc cattgttgct 60ttctccgttg tatggcaatg ataatggtaa cggattatgg tgggggaaca cattgaaggg 120agcatgggaa gctattcctg aagatgtaaa gccatatgca gcgattgaac ttcatcctgc 180aaaagtctgt aaaccaacaa gttgtattcc acgagatacg aaagaattga gagaatggta 240tgtcaagatg ttggaggaag ctcaaagtct aaacattcca gttttcttgg ttattatgtc 300ggctggagag cgtaatacag ttcctccaga gtggttagat gaacaattcc aaaagtatag 360tgtgttaaaa ggtgttttaa atattgagaa ttattggatt tacaataacc agttagctcc 420gcatagtgct aaatatttgg aagtttgtgc caaatatgga gcgcatttta tctggcatga 480tcatgaaaaa tggttctggg aaactattat gaatgatccg acattctttg aagcgagtca 540aaaatatcat aaaaatttgg tgttggcaac taaaaatacg ccaataagag atgatgcggg 600tacagattct atcgttagtg gattttggtt gagtggctta tgtgataact ggggctcatc 660aacagataca tggaaatggt gggaaaaaca ttatacaaac acatttgaaa ctggaagagc 720tagggatatg agatcctatg catcggaacc agaatcaatg attgctatgg aaatgatgaa 780tgtatatact gggggaggca cagtttataa tttcgaatgt gccgcgtata catttatgac 840aaatgatgta ccaactccag catttactaa aggtattatt cctttcttta gacatgctat 900acaaaatcca gctccaagta aggaagaagt tgtaaataga acaaaagctg tattttggaa 960tggagaaggt aggattagtt cattaaacgg attttatcaa ggactttatt cgaatgatga 1020aacaatgcct ttatataata atgggagata tcatattctt cctgtaatac atgagaaaat 1080tgataaggaa aagatttcat ctatattccc taatgcaaaa attttgacta aaaatagtga 1140ggaattgtct agtaaagtca actatttaaa ctcgctttat ccaaaacttt atgaaggaga 1200tgggtatgct cagcgtgtag gtaattcctg gtatatttat aatagtaatg ctaatatcaa 1260taaaaatcag caagtaatgt tgcctatgta tactaataat acaaagtcgt tatcgttaga 1320tttgacgcca catacttacg ctgttgttaa agaaaatcca aataatttac atattttatt 1380gaataattac aggacagata agacagctat gtgggcatta tcaggaaatt ttgatgcatc 1440aaaaagttgg aagaaagaag aattagagtt agcgaactgg ataagcaaaa attattccat 1500caatcctgta gataatgact ttaggacaac aacacttaca ttaaaagggc atactggtca 1560taaacctcag ataaatataa gtggcgataa aaatcattat acttatacag aaaattggga 1620tgagaatacc catgtttata ccattacggt taatcataat ggaatggtag agatgtctat 1680aaatactgag gggacaggtc cagtctcttt cccaacacca gataaattta atgatggtaa 1740tttgaatata gcatatgcaa aaccaacaac acaaagttct gtagattaca atggagaccc 1800taatagagct gtggatggta acagaaatgg taattttaac tctggttcgg taacacacac 1860tagggcagat aatccctctt ggtgggaagt cgatttgaaa aaaatggata aagttgggct 1920tgttaaaatt tataatcgca cagatgctga gactcaacgt ctatctaatt tt 1972204657PRTStreptococcus pneumoniae 204Lys Ala Asp Asn Arg Val Gln Met Arg Thr Thr Ile Asn Asn Glu Ser1 5 10 15Pro Leu Leu Leu Ser Pro Leu Tyr Gly Asn Asp Asn Gly Asn Gly Leu 20 25 30Trp Trp Gly Asn Thr Leu Lys Gly Ala Trp Glu Ala Ile Pro Glu Asp 35 40 45Val Lys Pro Tyr Ala Ala Ile Glu Leu His Pro Ala Lys Val Cys Lys 50 55 60Pro Thr Ser Cys Ile Pro Arg Asp Thr Lys Glu Leu Arg Glu Trp Tyr65 70 75 80Val Lys Met Leu Glu Glu Ala Gln Ser Leu Asn Ile Pro Val Phe Leu 85 90 95Val Ile Met Ser Ala Gly Glu Arg Asn Thr Val Pro Pro Glu Trp Leu 100 105 110Asp Glu Gln Phe Gln Lys Tyr Ser Val Leu Lys Gly Val Leu Asn Ile 115 120 125Glu Asn Tyr Trp Ile Tyr Asn Asn Gln Leu Ala Pro His Ser Ala Lys 130 135 140Tyr Leu Glu Val Cys Ala Lys Tyr Gly Ala His Phe Ile Trp His Asp145 150 155 160His Glu Lys Trp Phe Trp Glu Thr Ile Met Asn Asp Pro Thr Phe Phe 165 170 175Glu Ala Ser Gln Lys Tyr His Lys Asn Leu Val Leu Ala Thr Lys Asn 180 185 190Thr Pro Ile Arg Asp Asp Ala Gly Thr Asp Ser Ile Val Ser Gly Phe 195 200 205Trp Leu Ser Gly Leu Cys Asp Asn Trp Gly Ser Ser Thr Asp Thr Trp 210 215 220Lys Trp Trp Glu Lys His Tyr Thr Asn Thr Phe Glu Thr Gly Arg Ala225 230 235 240Arg Asp Met Arg Ser Tyr Ala Ser Glu Pro Glu Ser Met Ile Ala Met 245 250 255Glu Met Met Asn Val Tyr Thr Gly Gly Gly Thr Val Tyr Asn Phe Glu 260 265 270Cys Ala Ala Tyr Thr Phe Met Thr Asn Asp Val Pro Thr Pro Ala Phe 275 280 285Thr Lys Gly Ile Ile Pro Phe Phe Arg His Ala Ile Gln Asn Pro Ala 290 295 300Pro Ser Lys Glu Glu Val Val Asn Arg Thr Lys Ala Val Phe Trp Asn305 310 315 320Gly Glu Gly Arg Ile Ser Ser Leu Asn Gly Phe Tyr Gln Gly Leu Tyr 325 330 335Ser Asn Asp Glu Thr Met Pro Leu Tyr Asn Asn Gly Arg Tyr His Ile 340 345 350Leu Pro Val Ile His Glu Lys Ile Asp Lys Glu Lys Ile Ser Ser Ile 355 360 365Phe Pro Asn Ala Lys Ile Leu Thr Lys Asn Ser Glu Glu Leu Ser Ser 370 375 380Lys Val Asn Tyr Leu Asn Ser Leu Tyr Pro Lys Leu Tyr Glu Gly Asp385 390 395 400Gly Tyr Ala Gln Arg Val Gly Asn Ser Trp Tyr Ile Tyr Asn Ser Asn 405 410 415Ala Asn Ile Asn Lys Asn Gln Gln Val Met Leu Pro Met Tyr Thr Asn 420 425 430Asn Thr Lys Ser Leu Ser Leu Asp Leu Thr Pro His Thr Tyr Ala Val 435 440 445Val Lys Glu Asn Pro Asn Asn Leu His Ile Leu Leu Asn Asn Tyr Arg 450 455 460Thr Asp Lys Thr Ala Met Trp Ala Leu Ser Gly Asn Phe Asp Ala Ser465 470 475 480Lys Ser Trp Lys Lys Glu Glu Leu Glu Leu Ala Asn Trp Ile Ser Lys 485 490 495Asn Tyr Ser Ile Asn Pro Val Asp Asn Asp Phe Arg Thr Thr Thr Leu 500 505 510Thr Leu Lys Gly His Thr Gly His Lys Pro Gln Ile Asn Ile Ser Gly 515 520 525Asp Lys Asn His Tyr Thr Tyr Thr Glu Asn Trp Asp Glu Asn Thr His 530 535 540Val Tyr Thr Ile Thr Val Asn His Asn Gly Met Val Glu Met Ser Ile545 550 555 560Asn Thr Glu Gly Thr Gly Pro Val Ser Phe Pro Thr Pro Asp Lys Phe 565 570 575Asn Asp Gly Asn Leu Asn Ile Ala Tyr Ala Lys Pro Thr Thr Gln Ser 580 585 590Ser Val Asp Tyr Asn Gly Asp Pro Asn Arg Ala Val Asp Gly Asn Arg 595 600 605Asn Gly Asn Phe Asn Ser Gly Ser Val Thr His Thr Arg Ala Asp Asn 610 615 620Pro Ser Trp Trp Glu Val Asp Leu Lys Lys Met Asp Lys Val Gly Leu625 630 635 640Val Lys Ile Tyr Asn Arg Thr Asp Ala Glu Thr Gln Arg Leu Ser Asn 645 650 655Phe205811DNAStreptococcus pneumoniae 205ctgtggcaat cagtcagctg cttccaaaca gtcagcttca ggaacgattg aggtgatttc 60acgagaaaat ggctctggga cacggggtgc cttcacagaa atcacaggga ttctcaaaaa 120agacggtgat aaaaaaattg acaacactgc caaaacagct gtgattcaaa atagtacaga 180aggtgttctc tcagcagttc aagggaatgc taatgctatc ggctacatct ccttgggatc 240tttaacgaaa tctgtcaagg ctttagagat tgatggtgtc aaggctagtc gagacacagt 300tttagatggt gaataccctc ttcaacgtcc cttcaacatt gtttggtctt ctaatctttc 360caagctaggt caagatttta tcagctttat ccactccaaa caaggtcaac aagtggtcac 420agataataaa tttattgaag ctaaaaccga aaccacggaa tatacaagcc aacacttatc 480aggcaagttg tctgttgtag gttccacttc agtatcttct ttaatggaaa aattagcaga 540agcttataaa aaagaaaatc cagaagttac gattgatatt acctctaatg ggtcttcagc 600aggtattacc gctgttaagg agaaaaccgc tgatattggt atggtttcta gggaattaac 660tcctgaagaa ggtaagagtc tcacccatga tgctattgct ttagacggta ttgctgttgt 720ggtcaataat gacaataagg

caagccaagt cagtatggct gaacttgcag acgtttttag 780tggcaaatta accacctggg acaagattaa a 811206270PRTStreptococcus pneumoniae 206Cys Gly Asn Gln Ser Ala Ala Ser Lys Gln Ser Ala Ser Gly Thr Ile1 5 10 15Glu Val Ile Ser Arg Glu Asn Gly Ser Gly Thr Arg Gly Ala Phe Thr 20 25 30Glu Ile Thr Gly Ile Leu Lys Lys Asp Gly Asp Lys Lys Ile Asp Asn 35 40 45Thr Ala Lys Thr Ala Val Ile Gln Asn Ser Thr Glu Gly Val Leu Ser 50 55 60Ala Val Gln Gly Asn Ala Asn Ala Ile Gly Tyr Ile Ser Leu Gly Ser65 70 75 80Leu Thr Lys Ser Val Lys Ala Leu Glu Ile Asp Gly Val Lys Ala Ser 85 90 95Arg Asp Thr Val Leu Asp Gly Glu Tyr Pro Leu Gln Arg Pro Phe Asn 100 105 110Ile Val Trp Ser Ser Asn Leu Ser Lys Leu Gly Gln Asp Phe Ile Ser 115 120 125Phe Ile His Ser Lys Gln Gly Gln Gln Val Val Thr Asp Asn Lys Phe 130 135 140Ile Glu Ala Lys Thr Glu Thr Thr Glu Tyr Thr Ser Gln His Leu Ser145 150 155 160Gly Lys Leu Ser Val Val Gly Ser Thr Ser Val Ser Ser Leu Met Glu 165 170 175Lys Leu Ala Glu Ala Tyr Lys Lys Glu Asn Pro Glu Val Thr Ile Asp 180 185 190Ile Thr Ser Asn Gly Ser Ser Ala Gly Ile Thr Ala Val Lys Glu Lys 195 200 205Thr Ala Asp Ile Gly Met Val Ser Arg Glu Leu Thr Pro Glu Glu Gly 210 215 220Lys Ser Leu Thr His Asp Ala Ile Ala Leu Asp Gly Ile Ala Val Val225 230 235 240Val Asn Asn Asp Asn Lys Ala Ser Gln Val Ser Met Ala Glu Leu Ala 245 250 255Asp Val Phe Ser Gly Lys Leu Thr Thr Trp Asp Lys Ile Lys 260 265 270207805DNAStreptococcus pneumoniae 207ttgtcaacaa caacatgcta cttctgaggg gacgaatcaa aggcaaagca gttcagcgaa 60agttccatgg aaagcttcat acaccaacct aaacaaccag gtaagtacag aagaggtcaa 120atctctctta tcagctcact tggatccaaa tagtgttgat gcatttttta atctcgttaa 180tgactataat accattgtcg gctcaactgg cttatcagga gatttcactt cctttactca 240caccgaatac gatgttgaga aaatcagtca tctctggaat caaaagaagg gcgattttgt 300tgggaccaac tgccgtatca atagttattg tcttttgaaa aattcagtca ccattccaaa 360gcttgaaaag aatgaccagt tgcttttcct agataatgat gcgattgata aaggaaaggt 420ctttgattca caagataagg aagagtttga tattctattt tcgagagttc caactgagtc 480aactacagat gtcaaggttc acgctgaaaa gatggaagca ttcttctcac aatttcaatt 540caatgaaaaa gctcgaatgc tgtctgtagt cttgcacgac aatttggatg gcgagtatct 600gtttgtaggc cacgttgggg tcttagtacc tgctgatgac ggtttcttat ttgtagagaa 660attgactttc gaagagccct accaagcgat taaatttgct agtaaggaag attgctacaa 720gtatttgggc accaagtatg cggattatac aggcgaggga ctggctaagc cttttatcat 780ggataatgat aagtgggtta aactt 805208268PRTStreptococcus pneumoniae 208Cys Gln Gln Gln His Ala Thr Ser Glu Gly Thr Asn Gln Arg Gln Ser1 5 10 15Ser Ser Ala Lys Val Pro Trp Lys Ala Ser Tyr Thr Asn Leu Asn Asn 20 25 30Gln Val Ser Thr Glu Glu Val Lys Ser Leu Leu Ser Ala His Leu Asp 35 40 45Pro Asn Ser Val Asp Ala Phe Phe Asn Leu Val Asn Asp Tyr Asn Thr 50 55 60Ile Val Gly Ser Thr Gly Leu Ser Gly Asp Phe Thr Ser Phe Thr His65 70 75 80Thr Glu Tyr Asp Val Glu Lys Ile Ser His Leu Trp Asn Gln Lys Lys 85 90 95Gly Asp Phe Val Gly Thr Asn Cys Arg Ile Asn Ser Tyr Cys Leu Leu 100 105 110Lys Asn Ser Val Thr Ile Pro Lys Leu Glu Lys Asn Asp Gln Leu Leu 115 120 125Phe Leu Asp Asn Asp Ala Ile Asp Lys Gly Lys Val Phe Asp Ser Gln 130 135 140Asp Lys Glu Glu Phe Asp Ile Leu Phe Ser Arg Val Pro Thr Glu Ser145 150 155 160Thr Thr Asp Val Lys Val His Ala Glu Lys Met Glu Ala Phe Phe Ser 165 170 175Gln Phe Gln Phe Asn Glu Lys Ala Arg Met Leu Ser Val Val Leu His 180 185 190Asp Asn Leu Asp Gly Glu Tyr Leu Phe Val Gly His Val Gly Val Leu 195 200 205Val Pro Ala Asp Asp Gly Phe Leu Phe Val Glu Lys Leu Thr Phe Glu 210 215 220Glu Pro Tyr Gln Ala Ile Lys Phe Ala Ser Lys Glu Asp Cys Tyr Lys225 230 235 240Tyr Leu Gly Thr Lys Tyr Ala Asp Tyr Thr Gly Glu Gly Leu Ala Lys 245 250 255Pro Phe Ile Met Asp Asn Asp Lys Trp Val Lys Leu 260 265209508DNAStreptococcus pneumoniae 209ttgttcaggc aagtccgtga ctagtgaaca ccaaacgaaa gatgaaatga agacggagca 60gacagctagt aaaacaagcg cagctaaagg gaaagaggtg gctgattttg aattgatggg 120agtagatggc aagacctacc gtttatctga ttacaagggc aagaaagtct atctcaaatt 180ctgggcttct tggtgttcca tctgtctggc tagtcttcca gatacggatg agattgctaa 240agaagctggt gatgactatg tggtcttgac agtagtgtca ccaggacata agggagagca 300atctgaagcg gactttaaga attggtataa gggattggat tataaaaatc tcccagtcct 360agttgaccca tcaggcaaac ttttggaaac ttatggtgtc cgttcttacc caacccaagc 420ctttatagac aaagaaggca agctggtcaa aacacatcca ggattcatgg aaaaagatgc 480aattttgcaa actttgaagg aattagcc 508210169PRTStreptococcus pneumoniae 210Cys Ser Gly Lys Ser Val Thr Ser Glu His Gln Thr Lys Asp Glu Met1 5 10 15Lys Thr Glu Gln Thr Ala Ser Lys Thr Ser Ala Ala Lys Gly Lys Glu 20 25 30Val Ala Asp Phe Glu Leu Met Gly Val Asp Gly Lys Thr Tyr Arg Leu 35 40 45Ser Asp Tyr Lys Gly Lys Lys Val Tyr Leu Lys Phe Trp Ala Ser Trp 50 55 60Cys Ser Ile Cys Leu Ala Ser Leu Pro Asp Thr Asp Glu Ile Ala Lys65 70 75 80Glu Ala Gly Asp Asp Tyr Val Val Leu Thr Val Val Ser Pro Gly His 85 90 95Lys Gly Glu Gln Ser Glu Ala Asp Phe Lys Asn Trp Tyr Lys Gly Leu 100 105 110Asp Tyr Lys Asn Leu Pro Val Leu Val Asp Pro Ser Gly Lys Leu Leu 115 120 125Glu Thr Tyr Gly Val Arg Ser Tyr Pro Thr Gln Ala Phe Ile Asp Lys 130 135 140Glu Gly Lys Leu Val Lys Thr His Pro Gly Phe Met Glu Lys Asp Ala145 150 155 160Ile Leu Gln Thr Leu Lys Glu Leu Ala 165211994DNAStreptococcus pneumoniae 211ctcgcaaatt gaaaaggcgg cagttagcca aggaggaaaa gcagtgaaaa aaacagaaat 60tagtaaagac gcagacttgc acgaaattta tctagctgga ggttgtttct ggggagtgga 120ggaatatttc tcacgtgttc ccggggtgac ggatgccgtt tcaggctatg caaatggtag 180aggagaaaca accaagtacg aattgattaa ccaaacaggt catgcagaaa ccgtccatgt 240cacctatgat gccaagcaaa tttctctcaa ggaaatcctg cttcactatt tccgcattat 300caatccaacc agcaaaaata aacaaggaaa tgatgtgggg acccagtacc gtactggtgt 360ttattacaca gatgacaagg atttggaagt gattaaccaa gtctttgatg aggtggctaa 420gaaatacgat caacctctag cagttgaaaa ggaaaacttg aagaattttg tggtggctga 480ggattaccat caagactatc tcaagaaaaa tccaaatggc tactgccata tcaatgttaa 540tcaggcggcc tatcctgtca ttgatgccag caaatatcca aaaccaagtg atgaggaatt 600gaaaaagacc ctgtcacctg aggagtatgc agttacccag gaaaatcaaa cagaacgagc 660tttctcaaac cgttactggg ataaatttga atccggtatc tatgtggata tagcaactgg 720ggaacctctc ttttcatcaa aagacaaatt tgagtctggt tgtggctggc ctagttttac 780ccaacccatc agtccagatg ttgtcaccta caaggaagat aagtcctaca atatgacgcg 840tatggaagtg cggagccgag taggagattc tcaccttggg catgtcttta cggatggtcc 900acaggacaag ggcggcttac gttactgtat caatagcctc tctatccgct ttattcccaa 960agaccaaatg gaagaaaaag gtacgcttat ttac 994212331PRTStreptococcus pneumoniae 212Ser Gln Ile Glu Lys Ala Ala Val Ser Gln Gly Gly Lys Ala Val Lys1 5 10 15Lys Thr Glu Ile Ser Lys Asp Ala Asp Leu His Glu Ile Tyr Leu Ala 20 25 30Gly Gly Cys Phe Trp Gly Val Glu Glu Tyr Phe Ser Arg Val Pro Gly 35 40 45Val Thr Asp Ala Val Ser Gly Tyr Ala Asn Gly Arg Gly Glu Thr Thr 50 55 60Lys Tyr Glu Leu Ile Asn Gln Thr Gly His Ala Glu Thr Val His Val65 70 75 80Thr Tyr Asp Ala Lys Gln Ile Ser Leu Lys Glu Ile Leu Leu His Tyr 85 90 95Phe Arg Ile Ile Asn Pro Thr Ser Lys Asn Lys Gln Gly Asn Asp Val 100 105 110Gly Thr Gln Tyr Arg Thr Gly Val Tyr Tyr Thr Asp Asp Lys Asp Leu 115 120 125Glu Val Ile Asn Gln Val Phe Asp Glu Val Ala Lys Lys Tyr Asp Gln 130 135 140Pro Leu Ala Val Glu Lys Glu Asn Leu Lys Asn Phe Val Val Ala Glu145 150 155 160Asp Tyr His Gln Asp Tyr Leu Lys Lys Asn Pro Asn Gly Tyr Cys His 165 170 175Ile Asn Val Asn Gln Ala Ala Tyr Pro Val Ile Asp Ala Ser Lys Tyr 180 185 190Pro Lys Pro Ser Asp Glu Glu Leu Lys Lys Thr Leu Ser Pro Glu Glu 195 200 205Tyr Ala Val Thr Gln Glu Asn Gln Thr Glu Arg Ala Phe Ser Asn Arg 210 215 220Tyr Trp Asp Lys Phe Glu Ser Gly Ile Tyr Val Asp Ile Ala Thr Gly225 230 235 240Glu Pro Leu Phe Ser Ser Lys Asp Lys Phe Glu Ser Gly Cys Gly Trp 245 250 255Pro Ser Phe Thr Gln Pro Ile Ser Pro Asp Val Val Thr Tyr Lys Glu 260 265 270Asp Lys Ser Tyr Asn Met Thr Arg Met Glu Val Arg Ser Arg Val Gly 275 280 285Asp Ser His Leu Gly His Val Phe Thr Asp Gly Pro Gln Asp Lys Gly 290 295 300Gly Leu Arg Tyr Cys Ile Asn Ser Leu Ser Ile Arg Phe Ile Pro Lys305 310 315 320Asp Gln Met Glu Glu Lys Gly Thr Leu Ile Tyr 325 330213625DNAStreptococcus pneumoniae 213ttgtcagtca ggttctaatg gttctcagtc tgctgtggat gctatcaaac aaaaagggaa 60attagttgtg gcaaccagtc ctgactatgc accctttgaa tttcaatcat tggttgatgg 120aaagaaccag gtagtcggtg cagacatcga catggctcag gctatcgctg atgaacttgg 180ggttaagttg gaaatctcaa gcatgagttt tgacaatgtt ttgaccagtc ttcaaactgg 240taaggctgac ctagcagttg caggaattag tgctactgac gagagaaaag aagtctttga 300tttttcaatc ccatactatg aaaacaagat tagtttcttg gttcgtaagg ctgatgtgga 360aaaatacaag gatttaacta gcctagaaag tgctaatatt gcagcccaaa aagggactgt 420tccagaatca atggtcaagg aacaattgcc aaaagttcaa ttaacttccc taactaatat 480gggtgaagca gtcaatgaat tgcaggctgg aaaaatagat gctgttcata tggatgagcc 540tgttgcactt agttatgctg ctaaaaacgc tggcttagct gtcgcaactg tcagcttgaa 600gatgaaggac ggcgacgcca atgcc 625214208PRTStreptococcus pneumoniae 214Cys Gln Ser Gly Ser Asn Gly Ser Gln Ser Ala Val Asp Ala Ile Lys1 5 10 15Gln Lys Gly Lys Leu Val Val Ala Thr Ser Pro Asp Tyr Ala Pro Phe 20 25 30Glu Phe Gln Ser Leu Val Asp Gly Lys Asn Gln Val Val Gly Ala Asp 35 40 45Ile Asp Met Ala Gln Ala Ile Ala Asp Glu Leu Gly Val Lys Leu Glu 50 55 60Ile Ser Ser Met Ser Phe Asp Asn Val Leu Thr Ser Leu Gln Thr Gly65 70 75 80Lys Ala Asp Leu Ala Val Ala Gly Ile Ser Ala Thr Asp Glu Arg Lys 85 90 95Glu Val Phe Asp Phe Ser Ile Pro Tyr Tyr Glu Asn Lys Ile Ser Phe 100 105 110Leu Val Arg Lys Ala Asp Val Glu Lys Tyr Lys Asp Leu Thr Ser Leu 115 120 125Glu Ser Ala Asn Ile Ala Ala Gln Lys Gly Thr Val Pro Glu Ser Met 130 135 140Val Lys Glu Gln Leu Pro Lys Val Gln Leu Thr Ser Leu Thr Asn Met145 150 155 160Gly Glu Ala Val Asn Glu Leu Gln Ala Gly Lys Ile Asp Ala Val His 165 170 175Met Asp Glu Pro Val Ala Leu Ser Tyr Ala Ala Lys Asn Ala Gly Leu 180 185 190Ala Val Ala Thr Val Ser Leu Lys Met Lys Asp Gly Asp Ala Asn Ala 195 200 2052153022DNAStreptococcus pneumoniae 215ggaaacttca caggatttta aagagaagaa aacagcagtc attaaggaaa aagaagttgt 60tagtaaaaat cctgtgatag acaataacac tagcaatgaa gaagcaaaaa tcaaagaaga 120aaattccaat aaatcccaag gagattatac ggactcattt gtgaataaaa acacagaaaa 180tcccaaaaaa gaagataaag ttgtctatat tgctgaattt aaagataaag aatctggaga 240aaaagcaatc aaggaactat ccagtcttaa gaatacaaaa gttttatata cttatgatag 300aatttttaac ggtagtgcca tagaaacaac tccagataac ttggacaaaa ttaaacaaat 360agaaggtatt tcatcggttg aaagggcaca aaaagtccaa cccatgatga atcatgccag 420aaaggaaatt ggagttgagg aagctattga ttacctaaag tctatcaatg ctccgtttgg 480gaaaaatttt gatggtagag gtatggtcat ttcaaatatc gatactggaa cagattatag 540acataaggct atgagaatcg atgatgatgc caaagcctca atgagattta aaaaagaaga 600cttaaaaggc actgataaaa attattggtt gagtgataaa atccctcatg cgttcaatta 660ttataatggt ggcaaaatca ctgtagaaaa atatgatgat ggaagggatt attttgaccc 720acatgggatg catattgcag ggattcttgc tggaaatgat actgaacaag acatcaaaaa 780ctttaacggc atagatggaa ttgcacctaa tgcacaaatt ttctcttaca aaatgtattc 840tgacgcagga tctgggtttg cgggtgatga aacaatgttt catgctattg aagattctat 900caaacacaac gttgatgttg tttcggtatc atctggtttt acaggaacag gtcttgtagg 960tgagaaatat tggcaagcta ttcgggcatt aagaaaagca ggcattccaa tggttgtcgc 1020tacgggtaac tatgcgactt ctgcttcaag ttcttcatgg gatttagtag caaataatca 1080tctgaaaatg accgacactg gaaatgtaac acgaactgca gcacatgaag atgcgatagc 1140ggtcgcttct gctaaaaatc aaacagttga gtttgataaa gttaacatag gtggagaaag 1200ttttaaatac agaaatatag gggccttttt cgataagagt aaaatcacaa caaatgaaga 1260tggaacaaaa gctcctagta aattaaaatt tgtatatata ggcaaggggc aagaccaaga 1320tttgataggt ttggatctta ggggcaaaat tgcagtaatg gatagaattt atacaaagga 1380tttaaaaaat gcttttaaaa aagctatgga taagggtgca cgcgccatta tggttgtaaa 1440tactgtaaat tactacaata gagataattg gacagagctt ccagctatgg gatatgaagc 1500ggatgaaggt actaaaagtc aagtgttttc aatttcagga gatgatggtg taaagctatg 1560gaacatgatt aatcctgata aaaaaactga agtcaaaaga aataataaag aagattttaa 1620agataaattg gagcaatact atccaattga tatggaaagt tttaattcca acaaaccgaa 1680tgtaggtgac gaaaaagaga ttgactttaa gtttgcacct gacacagaca aagaactcta 1740taaagaagat atcatcgttc cagcaggatc tacatcttgg gggccaagaa tagatttact 1800tttaaaaccc gatgtttcag cacctggtaa aaatattaaa tccacgctta atgttattaa 1860tggcaaatca acttatggct atatgtcagg aactagtatg gcgactccaa tcgtggcagc 1920ttctactgtt ttgattagac cgaaattaaa ggaaatgctt gaaagacctg tattgaaaaa 1980tcttaaggga gatgacaaaa tagatcttac aagtcttaca aaaattgccc tacaaaatac 2040tgcgcgacct atgatggatg caacttcttg gaaagaaaaa agtcaatact ttgcatcacc 2100tagacaacag ggagcaggcc taattaatgt ggccaatgct ttgagaaatg aagttgtagc 2160aactttcaaa aacactgatt ctaaaggttt ggtaaactca tatggttcca tttctcttaa 2220agaaataaaa ggtgataaaa aatactttac aatcaagctt cacaatacat caaacagacc 2280tttgactttt aaagtttcag catcagcgat aactacagat tctctaactg acagattaaa 2340acttgatgaa acatataaag atgaaaaatc tccagatggt aagcaaattg ttccagaaat 2400tcacccagaa aaagtcaaag gagcaaatat cacatttgag catgatactt tcactatagg 2460cgcaaattct agctttgatt tgaatgcggt tataaatgtt ggagaggcca aaaacaaaaa 2520taaatttgta gaatcattta ttcattttga gtcagtggaa gcgatggaag ctctaaactc 2580cagcgggaag aaaataaact tccaaccttc tttgtcgatg cctctaatgg gatttgctgg 2640gaattggaac cacgaaccaa tccttgataa atgggcttgg gaagaagggt caagatcaaa 2700aacactggga ggttatgatg atgatggtaa accgaaaatt ccaggaacct taaataaggg 2760aattggtgga gaacatggta tagataaatt taatccagca ggagttatac aaaatagaaa 2820agataaaaat acaacatccc tggatcaaaa tccagaatta tttgctttca ataacgaagg 2880gatcaacgct ccatcatcaa gtggttctaa gattgctaac atttatcctt tagattcaaa 2940tggaaatcct caagatgctc aacttgaaag aggattaaca ccttctccac ttgtattaag 3000aagtgcagaa gaaggattga tt 30222161007PRTStreptococcus pneumoniae 216Glu Thr Ser Gln Asp Phe Lys Glu Lys Lys Thr Ala Val Ile Lys Glu1 5 10 15Lys Glu Val Val Ser Lys Asn Pro Val Ile Asp Asn Asn Thr Ser Asn 20 25 30Glu Glu Ala Lys Ile Lys Glu Glu Asn Ser Asn Lys Ser Gln Gly Asp 35 40 45Tyr Thr Asp Ser Phe Val Asn Lys Asn Thr Glu Asn Pro Lys Lys Glu 50 55 60Asp Lys Val Val Tyr Ile Ala Glu Phe Lys Asp Lys Glu Ser Gly Glu65 70 75 80Lys Ala Ile Lys Glu Leu Ser Ser Leu Lys Asn Thr Lys Val Leu Tyr 85 90 95Thr Tyr Asp Arg Ile Phe Asn Gly Ser Ala Ile Glu Thr Thr Pro Asp 100 105 110Asn Leu Asp Lys Ile Lys Gln Ile Glu Gly Ile Ser Ser Val Glu Arg 115 120 125Ala Gln Lys Val Gln Pro Met Met Asn His Ala Arg Lys Glu Ile Gly 130 135 140Val Glu Glu Ala Ile Asp Tyr Leu Lys Ser Ile Asn Ala Pro Phe Gly145

150 155 160Lys Asn Phe Asp Gly Arg Gly Met Val Ile Ser Asn Ile Asp Thr Gly 165 170 175Thr Asp Tyr Arg His Lys Ala Met Arg Ile Asp Asp Asp Ala Lys Ala 180 185 190Ser Met Arg Phe Lys Lys Glu Asp Leu Lys Gly Thr Asp Lys Asn Tyr 195 200 205Trp Leu Ser Asp Lys Ile Pro His Ala Phe Asn Tyr Tyr Asn Gly Gly 210 215 220Lys Ile Thr Val Glu Lys Tyr Asp Asp Gly Arg Asp Tyr Phe Asp Pro225 230 235 240His Gly Met His Ile Ala Gly Ile Leu Ala Gly Asn Asp Thr Glu Gln 245 250 255Asp Ile Lys Asn Phe Asn Gly Ile Asp Gly Ile Ala Pro Asn Ala Gln 260 265 270Ile Phe Ser Tyr Lys Met Tyr Ser Asp Ala Gly Ser Gly Phe Ala Gly 275 280 285Asp Glu Thr Met Phe His Ala Ile Glu Asp Ser Ile Lys His Asn Val 290 295 300Asp Val Val Ser Val Ser Ser Gly Phe Thr Gly Thr Gly Leu Val Gly305 310 315 320Glu Lys Tyr Trp Gln Ala Ile Arg Ala Leu Arg Lys Ala Gly Ile Pro 325 330 335Met Val Val Ala Thr Gly Asn Tyr Ala Thr Ser Ala Ser Ser Ser Ser 340 345 350Trp Asp Leu Val Ala Asn Asn His Leu Lys Met Thr Asp Thr Gly Asn 355 360 365Val Thr Arg Thr Ala Ala His Glu Asp Ala Ile Ala Val Ala Ser Ala 370 375 380Lys Asn Gln Thr Val Glu Phe Asp Lys Val Asn Ile Gly Gly Glu Ser385 390 395 400Phe Lys Tyr Arg Asn Ile Gly Ala Phe Phe Asp Lys Ser Lys Ile Thr 405 410 415Thr Asn Glu Asp Gly Thr Lys Ala Pro Ser Lys Leu Lys Phe Val Tyr 420 425 430Ile Gly Lys Gly Gln Asp Gln Asp Leu Ile Gly Leu Asp Leu Arg Gly 435 440 445Lys Ile Ala Val Met Asp Arg Ile Tyr Thr Lys Asp Leu Lys Asn Ala 450 455 460Phe Lys Lys Ala Met Asp Lys Gly Ala Arg Ala Ile Met Val Val Asn465 470 475 480Thr Val Asn Tyr Tyr Asn Arg Asp Asn Trp Thr Glu Leu Pro Ala Met 485 490 495Gly Tyr Glu Ala Asp Glu Gly Thr Lys Ser Gln Val Phe Ser Ile Ser 500 505 510Gly Asp Asp Gly Val Lys Leu Trp Asn Met Ile Asn Pro Asp Lys Lys 515 520 525Thr Glu Val Lys Arg Asn Asn Lys Glu Asp Phe Lys Asp Lys Leu Glu 530 535 540Gln Tyr Tyr Pro Ile Asp Met Glu Ser Phe Asn Ser Asn Lys Pro Asn545 550 555 560Val Gly Asp Glu Lys Glu Ile Asp Phe Lys Phe Ala Pro Asp Thr Asp 565 570 575Lys Glu Leu Tyr Lys Glu Asp Ile Ile Val Pro Ala Gly Ser Thr Ser 580 585 590Trp Gly Pro Arg Ile Asp Leu Leu Leu Lys Pro Asp Val Ser Ala Pro 595 600 605Gly Lys Asn Ile Lys Ser Thr Leu Asn Val Ile Asn Gly Lys Ser Thr 610 615 620Tyr Gly Tyr Met Ser Gly Thr Ser Met Ala Thr Pro Ile Val Ala Ala625 630 635 640Ser Thr Val Leu Ile Arg Pro Lys Leu Lys Glu Met Leu Glu Arg Pro 645 650 655Val Leu Lys Asn Leu Lys Gly Asp Asp Lys Ile Asp Leu Thr Ser Leu 660 665 670Thr Lys Ile Ala Leu Gln Asn Thr Ala Arg Pro Met Met Asp Ala Thr 675 680 685Ser Trp Lys Glu Lys Ser Gln Tyr Phe Ala Ser Pro Arg Gln Gln Gly 690 695 700Ala Gly Leu Ile Asn Val Ala Asn Ala Leu Arg Asn Glu Val Val Ala705 710 715 720Thr Phe Lys Asn Thr Asp Ser Lys Gly Leu Val Asn Ser Tyr Gly Ser 725 730 735Ile Ser Leu Lys Glu Ile Lys Gly Asp Lys Lys Tyr Phe Thr Ile Lys 740 745 750Leu His Asn Thr Ser Asn Arg Pro Leu Thr Phe Lys Val Ser Ala Ser 755 760 765Ala Ile Thr Thr Asp Ser Leu Thr Asp Arg Leu Lys Leu Asp Glu Thr 770 775 780Tyr Lys Asp Glu Lys Ser Pro Asp Gly Lys Gln Ile Val Pro Glu Ile785 790 795 800His Pro Glu Lys Val Lys Gly Ala Asn Ile Thr Phe Glu His Asp Thr 805 810 815Phe Thr Ile Gly Ala Asn Ser Ser Phe Asp Leu Asn Ala Val Ile Asn 820 825 830Val Gly Glu Ala Lys Asn Lys Asn Lys Phe Val Glu Ser Phe Ile His 835 840 845Phe Glu Ser Val Glu Ala Met Glu Ala Leu Asn Ser Ser Gly Lys Lys 850 855 860Ile Asn Phe Gln Pro Ser Leu Ser Met Pro Leu Met Gly Phe Ala Gly865 870 875 880Asn Trp Asn His Glu Pro Ile Leu Asp Lys Trp Ala Trp Glu Glu Gly 885 890 895Ser Arg Ser Lys Thr Leu Gly Gly Tyr Asp Asp Asp Gly Lys Pro Lys 900 905 910Ile Pro Gly Thr Leu Asn Lys Gly Ile Gly Gly Glu His Gly Ile Asp 915 920 925Lys Phe Asn Pro Ala Gly Val Ile Gln Asn Arg Lys Asp Lys Asn Thr 930 935 940Thr Ser Leu Asp Gln Asn Pro Glu Leu Phe Ala Phe Asn Asn Glu Gly945 950 955 960Ile Asn Ala Pro Ser Ser Ser Gly Ser Lys Ile Ala Asn Ile Tyr Pro 965 970 975Leu Asp Ser Asn Gly Asn Pro Gln Asp Ala Gln Leu Glu Arg Gly Leu 980 985 990Thr Pro Ser Pro Leu Val Leu Arg Ser Ala Glu Glu Gly Leu Ile 995 1000 10052171696DNAStreptococcus pneumoniae 217tgtggtcgaa gttgagactc ctcaatcaat aacaaatcag gagcaagcta ggacagaaaa 60ccaagtagta gagacagagg aagctccaaa agaagaagca cctaaaacag aagaaagtcc 120aaaggaagaa ccaaaatcgg aggtaaaacc tactgacgac acccttccta aagtagaaga 180ggggaaagaa gattcagcag aaccagctcc agttgaagaa gtaggtggag aagttgagtc 240aaaaccagag gaaaaagtag cagttaagcc agaaagtcaa ccatcagaca aaccagctga 300ggaatcaaaa gttgaacaag caggtgaacc agtcgcgcca agagaagacg aaaaggcacc 360agtcgagcca gaaaagcaac cagaagctcc tgaagaagag aaggctgtag aggaaacacc 420gaaacaagaa gagtcaactc cagataccaa ggctgaagaa actgtagaac caaaagagga 480gactgttaat caatctattg aacaaccaaa agttgaaacg cctgctgtag aaaaacaaac 540agaaccaaca gaggaaccaa aagttgaaca agcaggtgaa ccagtcgcgc caagagaaga 600cgaacaggca ccaacggcac cagttgagcc agaaaagcaa ccagaagttc ctgaagaaga 660gaaggctgta gaggaaacac cgaaaccaga agataaaata aagggtattg gtactaaaga 720accagttgat aaaagtgagt taaataatca aattgataaa gctagttcag tttctcctac 780tgattattct acagcaagtt acaatgctct tggacctgtt ttagaaactg caaaaggtgt 840ctatgcttca gagcctgtaa aacagcctga ggtaaatagc gagacaaata aacttaaaac 900ggctattgac gctctaaacg ttgataaaac tgaattaaac aatacgattg cagatgcaaa 960aacaaaggta aaagaacatt acagtgatag aagttggcaa aacctccaaa ctgaagttac 1020aaaggctgaa aaagttgcag ctaatacaga tgctaaacaa agtgaagtta acgaagctgt 1080tgaaaaatta actgcaacta ttgaaaaatt ggttgaatta tctgaaaagc caatattaac 1140attgactagt accgataaga aaatattgga acgtgaagct gttgctaagt atactctaga 1200aaatcaaaac aaaacaaaaa tcaaatcaat cacagctgaa ttgaaaaaag gagaagaagt 1260tattaatact gtagtcctta cagatgacaa ggtaacaaca gaaactataa gcgctgcatt 1320taagaaccta gagtactaca aagaatacac cctatctaca actatgattt acgacagagg 1380taacggtgaa gaaactgaaa ctctagaaaa tcaaaatatt caattagatc ttaaaaaagt 1440tgagcttaaa aatattaaac gtacagattt aatcaaatac gaaaatggaa aagaaactaa 1500tgaatcactg ataacaacta ttcctgatga taagagcaat tattatttaa aaataacttc 1560aaataatcag aaaactacat tactagctgt taaaaatata gaagaaacta cggttaacgg 1620aacacctgta tataaagtta cagcaatcgc agacaattta gtctctagaa ctgctgataa 1680taaatttgaa gaagaa 1696218565PRTStreptococcus pneumoniae 218Val Val Glu Val Glu Thr Pro Gln Ser Ile Thr Asn Gln Glu Gln Ala1 5 10 15Arg Thr Glu Asn Gln Val Val Glu Thr Glu Glu Ala Pro Lys Glu Glu 20 25 30Ala Pro Lys Thr Glu Glu Ser Pro Lys Glu Glu Pro Lys Ser Glu Val 35 40 45Lys Pro Thr Asp Asp Thr Leu Pro Lys Val Glu Glu Gly Lys Glu Asp 50 55 60Ser Ala Glu Pro Ala Pro Val Glu Glu Val Gly Gly Glu Val Glu Ser65 70 75 80Lys Pro Glu Glu Lys Val Ala Val Lys Pro Glu Ser Gln Pro Ser Asp 85 90 95Lys Pro Ala Glu Glu Ser Lys Val Glu Gln Ala Gly Glu Pro Val Ala 100 105 110Pro Arg Glu Asp Glu Lys Ala Pro Val Glu Pro Glu Lys Gln Pro Glu 115 120 125Ala Pro Glu Glu Glu Lys Ala Val Glu Glu Thr Pro Lys Gln Glu Glu 130 135 140Ser Thr Pro Asp Thr Lys Ala Glu Glu Thr Val Glu Pro Lys Glu Glu145 150 155 160Thr Val Asn Gln Ser Ile Glu Gln Pro Lys Val Glu Thr Pro Ala Val 165 170 175Glu Lys Gln Thr Glu Pro Thr Glu Glu Pro Lys Val Glu Gln Ala Gly 180 185 190Glu Pro Val Ala Pro Arg Glu Asp Glu Gln Ala Pro Thr Ala Pro Val 195 200 205Glu Pro Glu Lys Gln Pro Glu Val Pro Glu Glu Glu Lys Ala Val Glu 210 215 220Glu Thr Pro Lys Pro Glu Asp Lys Ile Lys Gly Ile Gly Thr Lys Glu225 230 235 240Pro Val Asp Lys Ser Glu Leu Asn Asn Gln Ile Asp Lys Ala Ser Ser 245 250 255Val Ser Pro Thr Asp Tyr Ser Thr Ala Ser Tyr Asn Ala Leu Gly Pro 260 265 270Val Leu Glu Thr Ala Lys Gly Val Tyr Ala Ser Glu Pro Val Lys Gln 275 280 285Pro Glu Val Asn Ser Glu Thr Asn Lys Leu Lys Thr Ala Ile Asp Ala 290 295 300Leu Asn Val Asp Lys Thr Glu Leu Asn Asn Thr Ile Ala Asp Ala Lys305 310 315 320Thr Lys Val Lys Glu His Tyr Ser Asp Arg Ser Trp Gln Asn Leu Gln 325 330 335Thr Glu Val Thr Lys Ala Glu Lys Val Ala Ala Asn Thr Asp Ala Lys 340 345 350Gln Ser Glu Val Asn Glu Ala Val Glu Lys Leu Thr Ala Thr Ile Glu 355 360 365Lys Leu Val Glu Leu Ser Glu Lys Pro Ile Leu Thr Leu Thr Ser Thr 370 375 380Asp Lys Lys Ile Leu Glu Arg Glu Ala Val Ala Lys Tyr Thr Leu Glu385 390 395 400Asn Gln Asn Lys Thr Lys Ile Lys Ser Ile Thr Ala Glu Leu Lys Lys 405 410 415Gly Glu Glu Val Ile Asn Thr Val Val Leu Thr Asp Asp Lys Val Thr 420 425 430Thr Glu Thr Ile Ser Ala Ala Phe Lys Asn Leu Glu Tyr Tyr Lys Glu 435 440 445Tyr Thr Leu Ser Thr Thr Met Ile Tyr Asp Arg Gly Asn Gly Glu Glu 450 455 460Thr Glu Thr Leu Glu Asn Gln Asn Ile Gln Leu Asp Leu Lys Lys Val465 470 475 480Glu Leu Lys Asn Ile Lys Arg Thr Asp Leu Ile Lys Tyr Glu Asn Gly 485 490 495Lys Glu Thr Asn Glu Ser Leu Ile Thr Thr Ile Pro Asp Asp Lys Ser 500 505 510Asn Tyr Tyr Leu Lys Ile Thr Ser Asn Asn Gln Lys Thr Thr Leu Leu 515 520 525Ala Val Lys Asn Ile Glu Glu Thr Thr Val Asn Gly Thr Pro Val Tyr 530 535 540Lys Val Thr Ala Ile Ala Asp Asn Leu Val Ser Arg Thr Ala Asp Asn545 550 555 560Lys Phe Glu Glu Glu 5652191879DNAStreptococcus pneumoniae 219aacacctgta tataaagtta cagcaatcgc agacaattta gtctctagaa ctgctgataa 60taaatttgaa gaagaatacg ttcactatat tgaaaaacct aaagtccacg aagataatgt 120atattataat ttcaaagaat tagtggaagc tattcaaaac gatccttcaa aagaatatcg 180tctgggacaa tcaatgagcg ctagaaatgt tgttcctaat ggaaaatcat atatcactaa 240agaattcaca ggaaaacttt taagttctga aggaaaacaa tttgctatta ctgaattgga 300acatccatta tttaatgtga taacaaacgc aacgataaat aatgtgaatt ttgaaaatgt 360agagatagaa cgttctggtc aagataatat tgcatcatta gccaatacta tgaaaggttc 420ttcagttatt acaaatgtca aaattacagg cacactttca ggtcgtaata atgttgctgg 480atttgtaaat aatatgaatg atggaactcg tattgaaaat gttgctttct ttggcaaact 540acactctaca agtggaaatg gctctcatac agggggaatt gcaggtacaa actatagagg 600aattgttaga aaagcatatg ttgatgctac tattacagga aacaaaacac gcgccagctt 660gttagttcct aaagtagatt atggattaac tctagaccat cttattggta caaaagctct 720cctaactgag tcggttgtaa aaggtaaaat agatgtttca aatccagtag aagttggagc 780aatagcaagt aagacttggc ctgtaggtac ggtaagtaat tctgtcagct atgctaagat 840tatccgtgga gaggagttat tcggctctaa cgacgttgat gattctgatt atgctagtgc 900tcatataaaa gatttatatg cggtagaggg atattcgtca ggtaatagat catttaggaa 960atctaaaaca tttactaaat taactaaaga acaagctgat gctaaagtta ctactttcaa 1020tattactgct gataaattag aaagtgatct atctcctctt gcaaaactta atgaagaaaa 1080agcctattct agtattcaag attataacgc tgaatataac caagcctata aaaatcttga 1140aaaattaata ccattctaca ataaagatta tattgtatat caaggtaata aattaaataa 1200agaacaccat ctaaatacta aagaagttct ttctgttacc gcgatgaaca acaatgagtt 1260tatcacaaac ctagatgaag ctaataaaat tattgttcac tatgcggacg gtacaaaaga 1320ttactttaac ttgtcttcta gcagtgaagg tttaagtaat gtaaaagaat atactataac 1380tgacttagga attaaatata cacctaatat cgttcaaaaa gataacacta ctcttgttaa 1440tgatataaaa tctattttag aatcagtaga gcttcagtct caaacgatgt atcagcatct 1500aaatcgatta ggtgactata gagttaatgc aatcaaagat ttatatttag aagaaagctt 1560cacagatgtt aaagaaaact taacaaacct aatcacaaaa ttagttcaaa acgaagaaca 1620tcaactaaat gattctccag ctgctcgtca aatgattcgt gataaagtcg agaaaaacaa 1680agcagcttta ttactaggtt taacttacct aaatcgttac tatggagtta aatttggtga 1740tgttaatatt aaagaattaa tgctattcaa accagatttc tatggtgaaa aagttagcgt 1800attagacaga ttaattgaaa tcggttctaa agagaacaac attaaaggtt cacgtacatt 1860cgacgcattc ggtcaagta 1879220626PRTStreptococcus pneumoniae 220Thr Pro Val Tyr Lys Val Thr Ala Ile Ala Asp Asn Leu Val Ser Arg1 5 10 15Thr Ala Asp Asn Lys Phe Glu Glu Glu Tyr Val His Tyr Ile Glu Lys 20 25 30Pro Lys Val His Glu Asp Asn Val Tyr Tyr Asn Phe Lys Glu Leu Val 35 40 45Glu Ala Ile Gln Asn Asp Pro Ser Lys Glu Tyr Arg Leu Gly Gln Ser 50 55 60Met Ser Ala Arg Asn Val Val Pro Asn Gly Lys Ser Tyr Ile Thr Lys65 70 75 80Glu Phe Thr Gly Lys Leu Leu Ser Ser Glu Gly Lys Gln Phe Ala Ile 85 90 95Thr Glu Leu Glu His Pro Leu Phe Asn Val Ile Thr Asn Ala Thr Ile 100 105 110Asn Asn Val Asn Phe Glu Asn Val Glu Ile Glu Arg Ser Gly Gln Asp 115 120 125Asn Ile Ala Ser Leu Ala Asn Thr Met Lys Gly Ser Ser Val Ile Thr 130 135 140Asn Val Lys Ile Thr Gly Thr Leu Ser Gly Arg Asn Asn Val Ala Gly145 150 155 160Phe Val Asn Asn Met Asn Asp Gly Thr Arg Ile Glu Asn Val Ala Phe 165 170 175Phe Gly Lys Leu His Ser Thr Ser Gly Asn Gly Ser His Thr Gly Gly 180 185 190Ile Ala Gly Thr Asn Tyr Arg Gly Ile Val Arg Lys Ala Tyr Val Asp 195 200 205Ala Thr Ile Thr Gly Asn Lys Thr Arg Ala Ser Leu Leu Val Pro Lys 210 215 220Val Asp Tyr Gly Leu Thr Leu Asp His Leu Ile Gly Thr Lys Ala Leu225 230 235 240Leu Thr Glu Ser Val Val Lys Gly Lys Ile Asp Val Ser Asn Pro Val 245 250 255Glu Val Gly Ala Ile Ala Ser Lys Thr Trp Pro Val Gly Thr Val Ser 260 265 270Asn Ser Val Ser Tyr Ala Lys Ile Ile Arg Gly Glu Glu Leu Phe Gly 275 280 285Ser Asn Asp Val Asp Asp Ser Asp Tyr Ala Ser Ala His Ile Lys Asp 290 295 300Leu Tyr Ala Val Glu Gly Tyr Ser Ser Gly Asn Arg Ser Phe Arg Lys305 310 315 320Ser Lys Thr Phe Thr Lys Leu Thr Lys Glu Gln Ala Asp Ala Lys Val 325 330 335Thr Thr Phe Asn Ile Thr Ala Asp Lys Leu Glu Ser Asp Leu Ser Pro 340 345 350Leu Ala Lys Leu Asn Glu Glu Lys Ala Tyr Ser Ser Ile Gln Asp Tyr 355 360 365Asn Ala Glu Tyr Asn Gln Ala Tyr Lys Asn Leu Glu Lys Leu Ile Pro 370 375 380Phe Tyr Asn Lys Asp Tyr Ile Val Tyr Gln Gly Asn Lys Leu Asn Lys385 390 395 400Glu His His Leu Asn Thr Lys Glu Val Leu Ser Val Thr Ala Met Asn 405 410 415Asn Asn Glu Phe Ile Thr Asn Leu Asp Glu Ala Asn Lys Ile Ile Val 420

425 430His Tyr Ala Asp Gly Thr Lys Asp Tyr Phe Asn Leu Ser Ser Ser Ser 435 440 445Glu Gly Leu Ser Asn Val Lys Glu Tyr Thr Ile Thr Asp Leu Gly Ile 450 455 460Lys Tyr Thr Pro Asn Ile Val Gln Lys Asp Asn Thr Thr Leu Val Asn465 470 475 480Asp Ile Lys Ser Ile Leu Glu Ser Val Glu Leu Gln Ser Gln Thr Met 485 490 495Tyr Gln His Leu Asn Arg Leu Gly Asp Tyr Arg Val Asn Ala Ile Lys 500 505 510Asp Leu Tyr Leu Glu Glu Ser Phe Thr Asp Val Lys Glu Asn Leu Thr 515 520 525Asn Leu Ile Thr Lys Leu Val Gln Asn Glu Glu His Gln Leu Asn Asp 530 535 540Ser Pro Ala Ala Arg Gln Met Ile Arg Asp Lys Val Glu Lys Asn Lys545 550 555 560Ala Ala Leu Leu Leu Gly Leu Thr Tyr Leu Asn Arg Tyr Tyr Gly Val 565 570 575Lys Phe Gly Asp Val Asn Ile Lys Glu Leu Met Leu Phe Lys Pro Asp 580 585 590Phe Tyr Gly Glu Lys Val Ser Val Leu Asp Arg Leu Ile Glu Ile Gly 595 600 605Ser Lys Glu Asn Asn Ile Lys Gly Ser Arg Thr Phe Asp Ala Phe Gly 610 615 620Gln Val6252211777DNAStreptococcus pneumoniae 221attagacaga ttaattgaaa tcggttctaa agagaacaac attaaaggtt cacgtacatt 60cgacgcattc ggtcaagtat tggctaaata tactaaatca ggtaatttag atgcattttt 120aaattataat agacaattgt tcacaaatat agacaatatg aacgattggt ttattgatgc 180tacagaagac catgtctaca tcgcagaacg cgcttctgag gtcgaagaaa ttaaaaattc 240taaacatcgt gcattcgata atttaaaacg aagtcacctt agaaatacta tactcccact 300actgaatatt gataaagcac atctttattt aatttcaaat tataatgcaa ttgcctttgg 360tagtgcagag cgattaggta aaaaatcatt agaagatatt aaagatatcg ttaacaaagc 420tgcagatggt tatagaaact attatgattt ctggtatcgt ctagcgtctg ataacgttaa 480acaacgacta ctaagagatg ctgttattcc tatttgggaa ggttataacg ctcctggtgg 540atgggttgaa aaatatggcc gctataatac cgacaaagta tatactcctc ttagagaatt 600ctttggtcct atggataagt attataatta taatggaaca ggagcttatg ctgctatata 660tcctaactct gatgatatta gaactgatgt aaaatatgtt catttagaaa tggttggtga 720atacggtatt tcagtttaca cacatgaaac aacacacgtc aacgaccgtg cgatttactt 780aggtggcttt ggacaccgtg aaggtactga tgctgaagca tatgctcagg gtatgctaca 840aactcctgtt actggtagtg gatttgatga gtttggttct ttaggtatta atatggtatt 900taaacgcaaa aatgatggga atcagtggta tattacagat ccaaaaactc taaaaacacg 960agaagatatt aatagatata tgaagggtta taatgacact ttaactcttc ttgatgaaat 1020tgaggctgaa tctgtgattt ctcaacaaaa taaagattta aatagtgcat ggttcaaaaa 1080aatagataga gaataccgtg ataacaataa attaaatcaa tgggataaaa ttcgaaatct 1140aagtcaagaa gagaaaaatg aattaaatat tcaatctgtt aatgatttag ttgatcaaca 1200attaatgact aatcgcaatc caggtaatgg tatctataaa cccgaagcaa ttagctataa 1260cgatcaatca ccttatgtag gtgttagaat gatgaccggt atctacggag gtaatactag 1320taaaggtgct cctggagctg tttcattcaa acataatgct tttagattat ggggttacta 1380cggatacgaa aatgggttct taggttatgc ttcaaataaa tataaacaac aatctaaaac 1440agatggtgag tctgttctaa gtgatgaata tattatcaag aaaatatcta acaatacatt 1500taatactatt gaagaattta aaaaagctta cttcaaagaa gttaaagata aagcaacgaa 1560aggattaaca acattcgaag taaatggttc ttccgtttca tcatacgatg atttactgac 1620attgtttaaa gaagctgtta aaaaagatgc cgaaactctt aaacaagaag caaacggtaa 1680taaaacagta tctatgaata atacagttaa attaaaagaa gctgtttata agaaacttct 1740tcaacaaaca aatagcttta aaacttcaat ctttaaa 1777222592PRTStreptococcus pneumoniae 222Leu Asp Arg Leu Ile Glu Ile Gly Ser Lys Glu Asn Asn Ile Lys Gly1 5 10 15Ser Arg Thr Phe Asp Ala Phe Gly Gln Val Leu Ala Lys Tyr Thr Lys 20 25 30Ser Gly Asn Leu Asp Ala Phe Leu Asn Tyr Asn Arg Gln Leu Phe Thr 35 40 45Asn Ile Asp Asn Met Asn Asp Trp Phe Ile Asp Ala Thr Glu Asp His 50 55 60Val Tyr Ile Ala Glu Arg Ala Ser Glu Val Glu Glu Ile Lys Asn Ser65 70 75 80Lys His Arg Ala Phe Asp Asn Leu Lys Arg Ser His Leu Arg Asn Thr 85 90 95Ile Leu Pro Leu Leu Asn Ile Asp Lys Ala His Leu Tyr Leu Ile Ser 100 105 110Asn Tyr Asn Ala Ile Ala Phe Gly Ser Ala Glu Arg Leu Gly Lys Lys 115 120 125Ser Leu Glu Asp Ile Lys Asp Ile Val Asn Lys Ala Ala Asp Gly Tyr 130 135 140Arg Asn Tyr Tyr Asp Phe Trp Tyr Arg Leu Ala Ser Asp Asn Val Lys145 150 155 160Gln Arg Leu Leu Arg Asp Ala Val Ile Pro Ile Trp Glu Gly Tyr Asn 165 170 175Ala Pro Gly Gly Trp Val Glu Lys Tyr Gly Arg Tyr Asn Thr Asp Lys 180 185 190Val Tyr Thr Pro Leu Arg Glu Phe Phe Gly Pro Met Asp Lys Tyr Tyr 195 200 205Asn Tyr Asn Gly Thr Gly Ala Tyr Ala Ala Ile Tyr Pro Asn Ser Asp 210 215 220Asp Ile Arg Thr Asp Val Lys Tyr Val His Leu Glu Met Val Gly Glu225 230 235 240Tyr Gly Ile Ser Val Tyr Thr His Glu Thr Thr His Val Asn Asp Arg 245 250 255Ala Ile Tyr Leu Gly Gly Phe Gly His Arg Glu Gly Thr Asp Ala Glu 260 265 270Ala Tyr Ala Gln Gly Met Leu Gln Thr Pro Val Thr Gly Ser Gly Phe 275 280 285Asp Glu Phe Gly Ser Leu Gly Ile Asn Met Val Phe Lys Arg Lys Asn 290 295 300Asp Gly Asn Gln Trp Tyr Ile Thr Asp Pro Lys Thr Leu Lys Thr Arg305 310 315 320Glu Asp Ile Asn Arg Tyr Met Lys Gly Tyr Asn Asp Thr Leu Thr Leu 325 330 335Leu Asp Glu Ile Glu Ala Glu Ser Val Ile Ser Gln Gln Asn Lys Asp 340 345 350Leu Asn Ser Ala Trp Phe Lys Lys Ile Asp Arg Glu Tyr Arg Asp Asn 355 360 365Asn Lys Leu Asn Gln Trp Asp Lys Ile Arg Asn Leu Ser Gln Glu Glu 370 375 380Lys Asn Glu Leu Asn Ile Gln Ser Val Asn Asp Leu Val Asp Gln Gln385 390 395 400Leu Met Thr Asn Arg Asn Pro Gly Asn Gly Ile Tyr Lys Pro Glu Ala 405 410 415Ile Ser Tyr Asn Asp Gln Ser Pro Tyr Val Gly Val Arg Met Met Thr 420 425 430Gly Ile Tyr Gly Gly Asn Thr Ser Lys Gly Ala Pro Gly Ala Val Ser 435 440 445Phe Lys His Asn Ala Phe Arg Leu Trp Gly Tyr Tyr Gly Tyr Glu Asn 450 455 460Gly Phe Leu Gly Tyr Ala Ser Asn Lys Tyr Lys Gln Gln Ser Lys Thr465 470 475 480Asp Gly Glu Ser Val Leu Ser Asp Glu Tyr Ile Ile Lys Lys Ile Ser 485 490 495Asn Asn Thr Phe Asn Thr Ile Glu Glu Phe Lys Lys Ala Tyr Phe Lys 500 505 510Glu Val Lys Asp Lys Ala Thr Lys Gly Leu Thr Thr Phe Glu Val Asn 515 520 525Gly Ser Ser Val Ser Ser Tyr Asp Asp Leu Leu Thr Leu Phe Lys Glu 530 535 540Ala Val Lys Lys Asp Ala Glu Thr Leu Lys Gln Glu Ala Asn Gly Asn545 550 555 560Lys Thr Val Ser Met Asn Asn Thr Val Lys Leu Lys Glu Ala Val Tyr 565 570 575Lys Lys Leu Leu Gln Gln Thr Asn Ser Phe Lys Thr Ser Ile Phe Lys 580 585 590223460DNAStreptococcus pneumoniae 223taagacagat gaacggagca aggtgtttga cttttccatt ccctactata ctgcaaaaaa 60taaactcatt gtcaaaaaat ctgacttgac tacttatcag tctgtaaacg acttggcgca 120gaaaaaggtt ggagcgcaga aaggttcgat tcaagagacg atggcgaaag atttgctaca 180aaattcttcc ctcgtatctc tgcctaaaaa tgggaattta atcacagatt taaaatcagg 240acaagtggat gccgttatct ttgaagaacc tgtttccaag ggatttgtgg aaaataatcc 300tgatttagca atcgcagacc tcaattttga aaaagagcaa gatgattcct acgcggtagc 360catgaaaaaa gatagcaaga aattgaagag gcagttcgat aaaaccattc aaaagttgaa 420ggagtctggg gaattagaca aactcattga ggaagcctta 460224153PRTStreptococcus pneumoniae 224Lys Thr Asp Glu Arg Ser Lys Val Phe Asp Phe Ser Ile Pro Tyr Tyr1 5 10 15Thr Ala Lys Asn Lys Leu Ile Val Lys Lys Ser Asp Leu Thr Thr Tyr 20 25 30Gln Ser Val Asn Asp Leu Ala Gln Lys Lys Val Gly Ala Gln Lys Gly 35 40 45Ser Ile Gln Glu Thr Met Ala Lys Asp Leu Leu Gln Asn Ser Ser Leu 50 55 60Val Ser Leu Pro Lys Asn Gly Asn Leu Ile Thr Asp Leu Lys Ser Gly65 70 75 80Gln Val Asp Ala Val Ile Phe Glu Glu Pro Val Ser Lys Gly Phe Val 85 90 95Glu Asn Asn Pro Asp Leu Ala Ile Ala Asp Leu Asn Phe Glu Lys Glu 100 105 110Gln Asp Asp Ser Tyr Ala Val Ala Met Lys Lys Asp Ser Lys Lys Leu 115 120 125Lys Arg Gln Phe Asp Lys Thr Ile Gln Lys Leu Lys Glu Ser Gly Glu 130 135 140Leu Asp Lys Leu Ile Glu Glu Ala Leu145 150225751DNAStreptococcus pneumoniae 225ctgtgagaat caagctacac ccaaagagac tagcgctcaa aagacaatcg tccttgctac 60agctggcgac gtgccaccat ttgactacga agacaagggc aatctgacag gctttgatat 120cgaagtttta aaggcagtag atgaaaaact cagcgactac gagattcaat tccaaagaac 180cgcctgggag agcatcttcc caggacttga ttctggtcac tatcaggctg cggccaataa 240cttgagttac acaaaagagc gtgctgaaaa atacctttac tcgcttccaa tttccaacaa 300tcccctcgtc cttgtcagca acaagaaaaa tcctttgact tctcttgacc agatcgctgg 360taaaacaaca caagaggata ccggaacttc taacgctcaa ttcatcaata actggaatca 420gaaacacact gataatcccg ctacaattaa tttttctggt gaggatattg gtaaacgaat 480cctagacctt gctaacggag agtttgattt cctagttttt gacaaggtat ccgttcaaaa 540gattatcaag gaccgtggtt tagacctctc agtcgttgat ttaccttctg cagatagccc 600cagcaattat atcattttct caagcgacca aaaagagttt aaagagcaat ttgataaagc 660gctcaaagaa ctctatcaag acggaaccct tgaaaaactc agcaatacct atctaggtgg 720ttcttacctc ccagatcaat ctcagttaca a 751226250PRTStreptococcus pneumoniae 226Cys Glu Asn Gln Ala Thr Pro Lys Glu Thr Ser Ala Gln Lys Thr Ile1 5 10 15Val Leu Ala Thr Ala Gly Asp Val Pro Pro Phe Asp Tyr Glu Asp Lys 20 25 30Gly Asn Leu Thr Gly Phe Asp Ile Glu Val Leu Lys Ala Val Asp Glu 35 40 45Lys Leu Ser Asp Tyr Glu Ile Gln Phe Gln Arg Thr Ala Trp Glu Ser 50 55 60Ile Phe Pro Gly Leu Asp Ser Gly His Tyr Gln Ala Ala Ala Asn Asn65 70 75 80Leu Ser Tyr Thr Lys Glu Arg Ala Glu Lys Tyr Leu Tyr Ser Leu Pro 85 90 95Ile Ser Asn Asn Pro Leu Val Leu Val Ser Asn Lys Lys Asn Pro Leu 100 105 110Thr Ser Leu Asp Gln Ile Ala Gly Lys Thr Thr Gln Glu Asp Thr Gly 115 120 125Thr Ser Asn Ala Gln Phe Ile Asn Asn Trp Asn Gln Lys His Thr Asp 130 135 140Asn Pro Ala Thr Ile Asn Phe Ser Gly Glu Asp Ile Gly Lys Arg Ile145 150 155 160Leu Asp Leu Ala Asn Gly Glu Phe Asp Phe Leu Val Phe Asp Lys Val 165 170 175Ser Val Gln Lys Ile Ile Lys Asp Arg Gly Leu Asp Leu Ser Val Val 180 185 190Asp Leu Pro Ser Ala Asp Ser Pro Ser Asn Tyr Ile Ile Phe Ser Ser 195 200 205Asp Gln Lys Glu Phe Lys Glu Gln Phe Asp Lys Ala Leu Lys Glu Leu 210 215 220Tyr Gln Asp Gly Thr Leu Glu Lys Leu Ser Asn Thr Tyr Leu Gly Gly225 230 235 240Ser Tyr Leu Pro Asp Gln Ser Gln Leu Gln 245 25022733DNAArtificial sequencePrimer 227gactggatcc taaaatctac gacaataaaa atc 3322827DNAArtificial sequencePrimer 228ctgagtcgac tggttgtgct ggttgag 2722930DNAArtificial sequencePrimer 229gtcaggatcc aaattacaat acggactatg 3023028DNAArtificial sequencePrimer 230cagtgtcgac taactctagg tcggaaac 2823135DNAArtificial sequencePrimer 231gactggatcc tgagaatcaa gctacaccca aagag 3523231DNAArtificial sequencePrimer 232agtcaagctt ttgtaactga gattgatctg g 3123337DNAArtificial sequencePrimer 233gactggatcc tggtaaccgc tcttctcgta acgcagc 3723432DNAArtificial sequencePrimer 234agtcaagctt tttcaggaac ttttacgctt cc 3223545DNAArtificial sequencePrimer 235agtcagatct tgtggaaatt tgacaggtaa cagcaaaaaa gctgc 4523633DNAArtificial sequencePrimer 236actgaagctt ttttgttttt caagaattca tcg 3323735DNAArtificial sequencePrimer 237gactggatcc tggtcaagga actgcttcta aagac 3523832DNAArtificial sequencePrimer 238agtcaagctt tcacaaattc gttggtgaag cc 3223938DNAArtificial sequencePrimer 239gactggatcc tagctcaggt ggaaacgctg gttcatcc 3824035DNAArtificial sequencePrimer 240agtcaagctt atcaactttt ccaccttcaa caacc 3524137DNAArtificial sequencePrimer 241gtcaagatct ctccaactat ggtaaatctg cggatgg 3724242DNAArtificial sequencePrimer 242agtcctgcag atccacatcc gctttcatcg ggttaaagaa gg 4224337DNAArtificial sequencePrimer 243gactggatcc tgggaaaaat tctagcgaaa ctagtgg 3724437DNAArtificial sequencePrimer 244gtcactgcag ctgtccttct tttacttctt tggttgc 3724540DNAArtificial sequencePrimer 245gactggatcc tgctagcgga aaaaaagata caacttctgg 4024637DNAArtificial sequencePrimer 246ctgaaagctt ttttgccaat ccttcagcaa tcttgtc 3724737DNAArtificial sequencePrimer 247gactagatct tggctcaaaa aatacagctt caagtcc 3724835DNAArtificial sequencePrimer 248agtcctgcag gtttttgttt gcttggtatt ggtcg 3524941DNAArtificial sequencePrimer 249gactggatcc tagtacaaac tcaagcacta gtcagacaga g 4125034DNAArtificial sequencePrimer 250cagtctgcag tttcaaagct ttttgtatgt cttc 3425137DNAArtificial sequencePrimer 251gactggatcc tggcaattct ggcggaagta aagatgc 3725236DNAArtificial sequencePrimer 252agtcaagctt gtttcatagc ttttttgatt gtttcg 3625340DNAArtificial sequencePrimer 253gactggatcc ttcacaagaa aaaacaaaaa atgaagatgg 4025431DNAArtificial sequencePrimer 254agtcaagctt atcgacgtag tctccgcctt c 3125538DNAArtificial sequencePrimer 255gactggatcc gaaaggtctg tggtcaaata atcttacc 3825637DNAArtificial sequencePrimer 256agtcaagctt agagttaaca tggtgcttgc caatagg 3725737DNAArtificial sequencePrimer 257gactggatcc aaactcagaa aagaaagcag acaatgc 3725836DNAArtificial sequencePrimer 258agtcaagctt ccaaactggt tgatccaaac catctg 3625936DNAArtificial sequencePrimer 259gactggatcc ttcgaaaggg tcagaaggtg cagacc 3626036DNAArtificial sequencePrimer 260agtcaagctt ctgtaggctt ggtgtgcccc agttgc 3626133DNAArtificial sequencePrimer 261ctgaggatcc ggggatggca gcttttaaaa atc 3326231DNAArtificial sequencePrimer 262cagtaagctt gtttacccat tcaccattac c 3126329DNAArtificial sequencePrimer 263cagtggatcc agacgagcaa aaaattaag 2926428DNAArtificial sequencePrimer 264tcagaagctt gtttacccat tcaccatt 2826535DNAArtificial sequencePrimer 265gactggatcc ctgtggtgag gaagaaacta aaaag 3526638DNAArtificial sequencePrimer 266ctgagtcgac aatattctgt aggaatgctt cgaatttg 3826738DNAArtificial sequencePrimer 267ctgaggatcc gacttttaac aataaaacta ttgaagag 3826833DNAArtificial sequencePrimer 268gtcactgcag gttgtcacct ccaaaaatca cgg 3326937DNAArtificial sequencePrimer 269gactggatcc ctttacaggt aaacaactac aagtcgg 3727032DNAArtificial sequencePrimer 270cagtaagctt ttcgaagttt ggctcagaat tg 3227132DNAArtificial sequencePrimer 271gactggatcc ccaggctgat acaagtatcg ca 3227231DNAArtificial sequencePrimer 272cagtaagctt atctgcagta tggctagatg g 3127337DNAArtificial sequencePrimer 273gactggatcc gtctgtatca tttgaaaaca aagaaac 3727432DNAArtificial sequencePrimer 274cagtctgcag ttttactgtt gctgtgcttg tg 3227539DNAArtificial sequencePrimer 275actgagatct tggtcaaaag gaaagtcaga caggaaagg 3927641DNAArtificial sequencePrimer 276cagtaagctt attcctgagc ttttttgata aaggttgcgc a 4127740DNAArtificial sequencePrimer

277actgggatcc gaaggataga tatattttag catttgagac 4027835DNAArtificial sequencePrimer 278agtcaagctt ccatggtatc aaaggcaaga cttgg 3527934DNAArtificial sequencePrimer 279gtcaggatcc ggtagttaaa gttggtatta acgg 3428036DNAArtificial sequencePrimer 280agtcaagctt gcaatttttg cgaagtattc caagag 3628137DNAArtificial sequencePrimer 281agtcggatcc ttcttacgag ttgggactgt atcaagc 3728240DNAArtificial sequencePrimer 282agtcaagctt gtttattttt tccttactta cagatgaagg 4028337DNAArtificial sequencePrimer 283agtcggatcc tactgagatg catcataatc taggagc 3728437DNAArtificial sequencePrimer 284tcagctcgag ttctttgaca tctccatcat aagtcgc 3728535DNAArtificial sequencePrimer 285gactggatcc ggttttgaga aagtatttgc agggg 3528639DNAArtificial sequencePrimer 286cagtaagctt ggattttttc atggatgcaa tttttttgg 3928743DNAArtificial sequencePrimer 287gactggatcc gacaacattt actatccata cagtagagtc agc 4328840DNAArtificial sequencePrimer 288gactaagctt ggcataaggt tgcaattctg gattaattgg 4028930DNAArtificial sequencePrimer 289gactggatcc ggctaaggaa agagtggatg 3029037DNAArtificial sequencePrimer 290gactaagctt ttcattttta aattgactat gcgcccg 3729136DNAArtificial sequencePrimer 291gactggatcc ttgttcctat gaacttggtc gtcacc 3629235DNAArtificial sequencePrimer 292catgaagctt atcctggatt tttccaagta aatct 3529334DNAArtificial sequencePrimer 293gactggatcc ttataagggt gaattagaaa aagg 3429433DNAArtificial sequencePrimer 294gactaagctt cttattagga ttgttagtag ttg 3329537DNAArtificial sequencePrimer 295gactggatcc gaatgttcag gctcaagaaa gttcagg 3729636DNAArtificial sequencePrimer 296gactaagctt ttcccctgat ggagcaaagt aatacc 3629740DNAArtificial sequencePrimer 297gactggatcc cttgggtgta acccatatcc agctccttcc 4029834DNAArtificial sequencePrimer 298gactgtcgac ttcagcttgt ttatctgggg ttgc 3429938DNAArtificial sequencePrimer 299gactggatcc tagtgatggt acttggcaag gaaaacag 3830035DNAArtificial sequencePrimer 300actgctgcag atctttgcca cctagcttct cattg 3530140DNAArtificial sequencePrimer 301gtcaggatcc tgggattcaa tatgtcagag atgatactag 4030235DNAArtificial sequencePrimer 302ctagaagctt acgcacccat tcaccattat cattg 3530335DNAArtificial sequencePrimer 303gtcaggatcc ggataataga gaagcattaa aaacc 3530436DNAArtificial sequencePrimer 304agtcaagctt gacaaaatct tgaaactcct ctggtc 3630535DNAArtificial sequencePrimer 305gtcaggatcc agattttgtc gaggagtgtc atacc 3530636DNAArtificial sequencePrimer 306agtcaagctt tcccttttta cccttacgaa tccagg 3630743DNAArtificial sequencePrimer 307gactggatcc atctgtagtt tatgcggatg aaacacttat tac 4330834DNAArtificial sequencePrimer 308gactgtcgac gctttggtag agatagaagt catg 3430938DNAArtificial sequencePrimer 309gactggatcc ttactttggt atcgtagata cagccggc 3831037DNAArtificial sequencePrimer 310agtcaagctt tgttaattgc gtaccttcta agcgacc 3731137DNAArtificial sequencePrimer 311gactggatcc agctaaggtt gcatgggatg cgattcg 3731234DNAArtificial sequencePrimer 312gactgtcgac ctgggcttta ttagtttgac tagc 3431333DNAArtificial sequencePrimer 313cagtggatcc ctatcactat gtaaataaag aga 3331430DNAArtificial sequencePrimer 314actgaagctt ttctgtccct gtttgaggca 3031534DNAArtificial sequencePrimer 315cagtggatcc tgagactcct caatcaataa caaa 3431634DNAArtificial sequencePrimer 316acgtaagctt ataatcagta ggagaaactg aact 3431730DNAArtificial sequencePrimer 317cagtggatcc ggatgctcaa gaaactgcgg 3031831DNAArtificial sequencePrimer 318gactaagctt ttgcctctca ttcttgcttc c 3131929DNAArtificial sequencePrimer 319cagtggatcc cgacaaaggt gagactgag 2932036DNAArtificial sequencePrimer 320acgtaagctt atttcttaat tcaagtgttt tctctg 3632134DNAArtificial sequencePrimer 321gactggatcc aaatcaattg gtagcacaag atcc 3432229DNAArtificial sequencePrimer 322cagtgtcgac attaggagcc actggtctc 2932331DNAArtificial sequencePrimer 323cagtggatcc caaacagtca gcttcaggaa c 3132430DNAArtificial sequencePrimer 324gactctgcag tttaatcttg tcccaggtgg 3032532DNAArtificial sequencePrimer 325gactggatcc attcgatgat gcggatgaaa ag 3232633DNAArtificial sequencePrimer 326gactaagctt catttgtctt tgggtatttc gca 3332730DNAArtificial sequencePrimer 327cagtggatcc ggagagtcga tcaaaagtag 3032828DNAArtificial sequencePrimer 328gtcactgcag ttgctcgtct cgaggttc 2832932DNAArtificial sequencePrimer 329cagtggatcc atggacaaca ggaaactggg ac 3233033DNAArtificial sequencePrimer 330cagtaagctt attagcttct gtacctgtgt ttg 3333141DNAArtificial sequencePrimer 331gactggatcc cgatgggctc aatccaaccc caggtcaagt c 4133240DNAArtificial sequencePrimer 332gactctgcag catagcttta tcctctgaca tcatcgtatc 4033334DNAArtificial sequencePrimer 333gactggatcc ttccaatcaa aaacaggcag atgg 3433430DNAArtificial sequencePrimer 334gactaagctt gagtcccata gtccaaggca 3033538DNAArtificial sequencePrimer 335agtcggatcc tatcacagga tcgaacggta agacaacc 3833634DNAArtificial sequencePrimer 336actggtcgac ttcttttaac tccgctactg tgtc 3433738DNAArtificial sequencePrimer 337cagtggatcc aagttcatcg aagatggttg ggaagtcc 3833832DNAArtificial sequencePrimer 338gatcgtcgac ccgctcccac atgctcaacc tt 3233937DNAArtificial sequencePrimer 339tgacggatcc atcgctagct agtgaaatgc aagaaag 3734037DNAArtificial sequencePrimer 340tgacaagctt attcgttttt gaactagttg ctttcgt 3734137DNAArtificial sequencePrimer 341gactggatcc gcaccagatg gggcacaagg ttcaggg 3734235DNAArtificial sequencePrimer 342tgacaagctt aacttgtaac gaacagttca atctg 3534336DNAArtificial sequencePrimer 343gactagatct ttttaaccca actgttggta ctttcc 3634434DNAArtificial sequencePrimer 344tgacaagctt gttaggtgtt acattttgac cgtc 3434535DNAArtificial sequencePrimer 345actgagatct ttttaaccca actgttggta ctttc 3534637DNAArtificial sequencePrimer 346gactaagctt tctacgataa cgatcatttt ctttacc 3734738DNAArtificial sequencePrimer 347gactgtcgac tcgtagatat ttaagtctaa gtgaagcg 3834834DNAArtificial sequencePrimer 348agtcaagctt gttaggtgtt acattttgca agtc 3434932DNAArtificial sequencePrimer 349gactggatcc ctttggtttt gaaggaagta ag 3235037DNAArtificial sequencePrimer 350tgacctgcag acgatttttg aaaaatggag gtgtatc 3735131DNAArtificial sequencePrimer 351cagtggatcc ctactacctc tcgagagaaa g 3135232DNAArtificial sequencePrimer 352actgaagctt ttcgcttttt actcgtttga ca 3235342DNAArtificial sequencePrimer 353cagtggatcc taaggtcaaa agtcagaccg ctaagaaagt gc 4235438DNAArtificial sequencePrimer 354cagtaagctt tagggtatcc aaatactggt tgttgatg 3835536DNAArtificial sequencePrimer 355tgacagatct tgacgggtct caggatcaga ctcagg 3635636DNAArtificial sequencePrimer 356tgacaagctt caaagacatc cacctcttga cctttg 3635738DNAArtificial sequencePrimer 357gactggatcc tagaggcttt gccaaatggt gggaaggg 3835840DNAArtificial sequencePrimer 358gtcagtcgac ttgttgtaac acttttcgag gtttggtacc 4035933DNAArtificial sequencePrimer 359cagtggatcc tcaaaaagag aaggaaaact tgg 3336034DNAArtificial sequencePrimer 360cagtctgcag tttcttcaac aaaccttgtt cttg 3436131DNAArtificial sequencePrimer 361cagtggatcc acgttctatt gaggaccact t 3136234DNAArtificial sequencePrimer 362cagtaagctt ttccttctca gtcaattctt ttcc 3436335DNAArtificial sequencePrimer 363gactggatcc cgctcaaaat accagaggtg ttcag 3536436DNAArtificial sequencePrimer 364gactaagctt agtaccatgg gtgtgacagg tttgaa 3636535DNAArtificial sequencePrimer 365ctgaggatcc aattgtacaa ttagaaaaag atagc 3536634DNAArtificial sequencePrimer 366tgacaagctt gcgttgacta ggttctgcaa tgcc 3436740DNAArtificial sequencePrimer 367gactggatcc tctgaccaag caaaaagaag cagtcaatga 4036834DNAArtificial sequencePrimer 368tcagcagctg atcattgact ttacgatttg ctcc 3436941DNAArtificial sequencePrimer 369gactggatcc gtccggctct gtccagtcca ctttttcagc g 4137033DNAArtificial sequencePrimer 370tcagaagctt attttttgtt tccttaatgc gtt 3337139DNAArtificial sequencePrimer 371gactggatcc gggacaaatt caaaaaaata ggcaagagg 3937234DNAArtificial sequencePrimer 372gtcaaagctt tggctctttg attgccaaca actg 3437339DNAArtificial sequencePrimer 373gactggatcc tcgctaccag caacaaagcg agcaaaagg 3937432DNAArtificial sequencePrimer 374gactaagctt acttttttct ttttccacac ga 3237539DNAArtificial sequencePrimer 375cagtggatcc gaaccgacaa gtcgcccact atcaagact 3937633DNAArtificial sequencePrimer 376ctgaaagctt tgaattctct ttcttttcag gct 3337736DNAArtificial sequencePrimer 377tcgaggatcc ggttgtcggc tggcaatata tcccgt 3637837DNAArtificial sequencePrimer 378cagtaagctt ccgaacccat tcgccattat agttgac 3737935DNAArtificial sequencePrimer 379agtcggatcc ggccaaatca gaatgggtag aagac 3538034DNAArtificial sequencePrimer 380tgacctgcag cttctcattg attttcatca tcac 3438135DNAArtificial sequencePrimer 381gactggatcc atttgcagat gattctgaag gatgg 3538238DNAArtificial sequencePrimer 382tcagctgcag cttaacccat tcaccattct agtttaag 3838337DNAArtificial sequencePrimer 383gactggatcc tgtcgctgca aatgaaactg aagtagc 3738434DNAArtificial sequencePrimer 384gactaagctt ataccaaacg ctgacatcta cgcg 3438537DNAArtificial sequencePrimer 385agtcagatct tacgtctcag cctacttttg taagagc 3738634DNAArtificial sequencePrimer 386gactaagctt aacccattca ccattggcat tgac 3438741DNAArtificial sequencePrimer 387cagtggatcc tggacaggtg aaaggtcatg ctacatttgt g 4138833DNAArtificial sequencePrimer 388gactaagctt caaccattga gaccttgcaa cac 3338941DNAArtificial sequencePrimer 389gtcaggatcc gattgctcct ttgaaggatt tgagagaaac c 4139041DNAArtificial sequencePrimer 390gactaagctt cgatcaaaga taagataaat atatataaag t 4139147DNAArtificial sequencePrimer 391gactggatcc taggtcatat gggacttttt ttctacaaca aaatagg 4739237DNAArtificial sequencePrimer 392tgacaagctt atctatcagc tcatttaatc gtttttg 3739335DNAArtificial sequencePrimer 393ctgaggatcc caacgttgag aattatttgc gaatg 3539431DNAArtificial sequencePrimer 394tgacaagctt gagtctacaa aagtaatgta c 3139535DNAArtificial sequencePrimer 395gtcaggatcc ctactatcaa tcaagttctt cagcc 3539637DNAArtificial sequencePrimer 396tgacaagctt gactgaggct tggaccagat tgaaaag 3739736DNAArtificial sequencePrimer 397gactggatcc gacaaaaaca ttaaaacgtc ctgagg 3639834DNAArtificial sequencePrimer 398gactaagctt agcacgaact gtgacgctgg ttcc 3439935DNAArtificial sequencePrimer 399gactggatcc ttctcaggag acctttaaaa atatc 3540031DNAArtificial sequencePrimer 400gactaagctt gttggccatc ttgtacatac c 3140131DNAArtificial sequencePrimer 401gactggatcc agtaaatgcg caatcaaatt c 3140237DNAArtificial sequencePrimer 402agtcctgcag gtatttagcc caataatcta taaagct 3740332DNAArtificial sequencePrimer 403cagtggatcc ttaccgcgtt catcaagatg tc 3240432DNAArtificial sequencePrimer 404gactaagctt gccagatgtt gaaaagagag tg 3240540DNAArtificial sequencePrimer 405gactggatcc gtggatgggc tttaactatc ttcgtattcg 4040633DNAArtificial sequencePrimer 406agtcaagctt gctagtcttc actttccctt tcc 3340734DNAArtificial sequencePrimer 407gactgtcgac actaaaccag catcgttcgc agga 3440835DNAArtificial sequencePrimer 408ctgactgcag cttcttgaag aaataatgat tgtgg 3540932DNAArtificial sequencePrimer 409cagtggatcc tgactacctt gaaatcccac tt 3241039DNAArtificial sequencePrimer 410cagtaagctt ttttttaagg ttgtagaatg atttcaatc 3941135DNAArtificial sequencePrimer 411cagtgtcgac tcgtatcttt ttttggagca atgtt 3541233DNAArtificial sequencePrimer 412gactaagctt aaatgttccg atacgggtga ttg 3341333DNAArtificial sequencePrimer 413cagtggatcc ggactctctc aaagatgtga aag 3341434DNAArtificial sequencePrimer 414gactaagctt cttgagtttg tcaaggattg cttt 3441538DNAArtificial sequencePrimer 415cagtggatcc caagaaatcc tatcatctct tccagaag 3841633DNAArtificial sequencePrimer 416gactaagctt ttcagaacta aaagccgcag ctt 3341730DNAArtificial sequencePrimer 417gactggatcc acgaaatgca gggcagacag 3041836DNAArtificial sequencePrimer 418cagtaagctt atcaacataa tctagtaaat aagcgt 3641936DNAArtificial sequencePrimer 419cagtggatcc tgtatagttt ttagcgcttg ttcttc 3642036DNAArtificial sequencePrimer 420gtcaaagctt tgatagagtg tcataatctt ctttag 3642132DNAArtificial sequencePrimer 421gactggatcc gtgtgtcgag catattctga ag 3242237DNAArtificial sequencePrimer 422cagtaagctt acttttacca tttctttgtt ctgcatc 3742338DNAArtificial sequencePrimer 423gactgtcgac gtgtttggat agcattcaga atcagacg 3842432DNAArtificial sequencePrimer 424cagtaagctt cggaagtaaa gacaattttt cc 3242537DNAArtificial sequencePrimer 425cagtggatcc gtgcctagat agtattatta ctcaaac 3742634DNAArtificial sequencePrimer 426gactaagctt tttgcttatt tctctcaatt tttc 3442736DNAArtificial sequencePrimer 427cagtggatcc cattcagaag cagacctatc aaaatc 3642843DNAArtificial sequencePrimer 428actgaagctt atgtaatttt ttagattttt caatattttt cag 4342935DNAArtificial sequencePrimer 429agtcggatcc taaggctgat aatcgtgttc aaatg 3543031DNAArtificial sequencePrimer 430gactaagctt aaaattagat agacgttgag t 3143135DNAArtificial sequencePrimer 431agtcggatcc ctgtggcaat cagtcagctg cttcc 3543240DNAArtificial sequencePrimer 432gactgtcgac tttaatcttg tcccaggtgg ttaatttgcc 4043338DNAArtificial sequencePrimer 433actggtcgac ttgtcaacaa caacatgcta cttctgag 3843435DNAArtificial sequencePrimer 434gactctgcag aagtttaacc cacttatcat tatcc 3543539DNAArtificial sequencePrimer 435actgggatcc ttgttcaggc aagtccgtga ctagtgaac 3943633DNAArtificial sequencePrimer 436gactaagctt ggctaattcc ttcaaagttt gca 3343739DNAArtificial sequencePrimer 437agtcggatcc ctcgcaaatt gaaaaggcgg cagttagcc 3943835DNAArtificial sequencePrimer 438gactaagctt gtaaataagc gtaccttttt cttcc 3543938DNAArtificial sequencePrimer 439tcagggatcc ttgtcagtca ggttctaatg gttctcag 3844032DNAArtificial sequencePrimer 440agtcaagctt ggcattggcg tcgccgtcct tc 3244138DNAArtificial sequencePrimer 441gactggatcc ggaaacttca caggatttta aagagaag 3844234DNAArtificial sequencePrimer 442gactgtcgac aatcaatcct tcttctgcac ttct 3444337DNAArtificial sequencePrimer 443cagtggatcc tgtggtcgaa gttgagactc ctcaatc 3744431DNAArtificial sequencePrimer 444gactaagctt ttcttcaaat ttattatcag c

3144539DNAArtificial sequencePrimer 445agtcggatcc aacacctgta tataaagtta cagcaatcg 3944637DNAArtificial sequencePrimer 446gactgtcgac tacttgaccg aatgcgtcga atgtacg 3744734DNAArtificial sequencePrimer 447ctgaggatcc attagacaga ttaattgaaa tcgg 3444834DNAArtificial sequencePrimer 448gactgtcgac tttaaagatt gaagttttaa agct 3444935DNAArtificial sequencePrimer 449tgacggatcc taagacagat gaacggagca aggtg 3545035DNAArtificial sequencePrimer 450ctgaaagctt taaggcttcc tcaatgagtt tgtct 3545133DNAArtificial sequencePrimer 451gactggatcc ctgtgagaat caagctacac cca 3345234DNAArtificial sequencePrimer 452ctgaaagctt ttgtaactga gattgatctg ggag 344534PRTArtificial sequenceLipoprotein cleavage consensus sequence 453Leu Xaa Xaa Cys14546PRTArtificial sequenceHighly conserved sequence from anchored surface proteins from gram-positive bacteria 454Leu Pro Xaa Thr Gly Xaa1 5

Claims

1. An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of: (a) a nucleotide sequence encoding any of the amino acid sequences of the polypeptides shown in Table 1; and (b) a nucleotide sequence complementary to any of the nucleotide sequences in (a).

2. An isolated nucleic acid molecule comprising a polynucleotide which hybridizes under stringent hybridization conditions to a polynucleotide having a nucleotide sequence identical to a nucleotide sequence in (a) or (b) of claim 1 wherein said polynucleotide which hybridizes does not hybridize under stringent hybridization conditions to a polynucleotide having a nucleotide sequence consisting of only A residues or of only T residues.

3. An isolated nucleic acid molecule comprising a polynucleotide which encodes the amino acid sequence of an epitope-bearing portion of a polypeptide having an amino acid sequence in (a) of claim 1.

4. The isolated nucleic acid molecule of claim 3, wherein said epitope-bearing portion of a polypeptide has an amino acid sequence listed in Table 2.

5. A method for making a recombinant vector comprising inserting an isolated nucleic acid molecule of claim 1 into a vector.

6. A recombinant vector produced by the method of claim 5.

7. A method of making a recombinant host cell comprising introducing the recombinant vector of claim 6 into a host cell.

8. A recombinant host cell produced by the method of claim 7.

9. A method of producing a polypeptide encoded by said isolated nucleic acid molecule comprising culturing the host cell of claim 8 under conditions favoring expressing the heterologous polypeptide.

10. A polypeptide produced according to the method of claim 9.

11. An isolated polypeptide comprising an amino acid sequence at least 70% identical to a sequence selected from the group consisting of an amino acid sequence of any of the polypeptides described in Table 1.

12. An isolated polypeptide antigen comprising an amino acid sequence of an S. pneumoniae epitope shown in Table 2.

13. An isolated nucleic acid molecule comprising a polynucleotide with a nucleotide sequence encoding a polypeptide of claim 9.

14. An isolated antibody that binds specifically to a polypeptide of claim 11.

15. A hybridoma which produces an antibody according to claim 14.

16. A vaccine, comprising: (1) one of more S. pneumoniae polypeptides selected from the group consisting of a polypeptide comprising an amino acid sequence identified in Table 1, or a fragment thereof; and (2) a pharmaceutically acceptable diluent, carrier, or excipient; wherein said polypeptide is present, in an amount effective to elicit protective antibodies in an animal to a member of the Streptococcus genus.

17. A method of preventing or attenuating an infection caused by a member of the Streptococcus genus in an animal, comprising administering to said animal a polypeptide of claim 11, wherein said polypeptide is administered in an amount effective to prevent or attenuate said infection.

18. A method of detecting Streptococcus nucleic acids in a biological sample obtained from an animal involving assaying for one or more nucleic acid sequences encoding Streptococcus polypeptides in a sample comprising: (a) contacting the sample with one or more of the isolated nucleic acid molecules of claim 2, under conditions such that hybridization occurs, and (b) detecting hybridization of said one or more molecules to the one or more Streptococcus nucleic acid sequences present in the biological sample.

19. A kit for detecting Streptococcus antibodies in a biological sample obtained from an animal, comprising: (a) a polypeptide of claim 12 attached to a solid support; and (b) detecting means.

20. A method of detecting Streptococcus antibodies in a biological sample obtained from an animal, comprising (a) contacting the sample with a polypeptide of claim 12; and (b) detecting antibody-antigen complexes.