U.S. patent application number 13/369411 was filed with the patent office on 2013-06-13 for therapeutic tb vaccine.
This patent application is currently assigned to Statens Serum Institut. The applicant listed for this patent is PETER ANDERSEN, Ida Rosenkrands, Anette Stryhn. Invention is credited to PETER ANDERSEN, Ida Rosenkrands, Anette Stryhn.
Application Number | 20130149324 13/369411 |
Document ID | / |
Family ID | 30011018 |
Filed Date | 2013-06-13 |
United States Patent
Application |
20130149324 |
Kind Code |
A1 |
ANDERSEN; PETER ; et
al. |
June 13, 2013 |
THERAPEUTIC TB VACCINE
Abstract
Therapeutic vaccines comprising polypeptides expressed during
the latent stage of mycobacteria infection are provided, as are
multiphase vaccines, and methods for treating and preventing
tuberculosis.
Inventors: |
ANDERSEN; PETER; (Bronshoj,
DK) ; Rosenkrands; Ida; (Vaerlose, DK) ;
Stryhn; Anette; (Virum, DK) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ANDERSEN; PETER
Rosenkrands; Ida
Stryhn; Anette |
Bronshoj
Vaerlose
Virum |
|
DK
DK
DK |
|
|
Assignee: |
Statens Serum Institut
Copenhagen S
DK
|
Family ID: |
30011018 |
Appl. No.: |
13/369411 |
Filed: |
February 9, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12785053 |
May 21, 2010 |
8142797 |
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13369411 |
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10617038 |
Jul 11, 2003 |
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12785053 |
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60401725 |
Aug 7, 2002 |
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Current U.S.
Class: |
424/190.1 |
Current CPC
Class: |
A61K 39/04 20130101;
A61P 31/06 20180101; A61K 2300/00 20130101; C07K 14/35 20130101;
A61K 39/04 20130101; A61K 2039/55572 20130101 |
Class at
Publication: |
424/190.1 |
International
Class: |
C07K 14/35 20060101
C07K014/35 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 13, 2002 |
DK |
PA 2002 01098 |
Claims
1. A method for inducing an immune response in an animal to
tuberculosis, comprising delivering a composition comprising a
mycobacteria polypeptide having amino acid sequence SEQ ID NO: 33
and a pharmaceutically acceptable polymeric carrier bound to the
polypeptide or a pharmaceutically acceptable adjuvant.
2. The method according to claim 1, wherein said polypeptide is
fused to at least one fusion partner which is an antigen expressed
by bacteria within the mycobacteria family, wherein said at least
one fusion partner is heterologous to said polypeptide.
3. The method according to claim 1, wherein said polypeptide is
lipidated thereby providing a self-adjuvanting effect of the
polypeptide.
4. The method according to claim 1, which comprises a polymeric
carrier bound by covalent or non-covalent interactions to said
polypeptide.
5. The method according to claim 4, wherein the polymeric carrier
is a polystyrene.
6. The method according to claim 2, wherein the fusion partner is
selected from the polypeptides of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7,
8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24,
25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42,
43, 44, and 45.
7. The method according to claim 6, wherein the polypeptides are
recombinant or synthetic and are delivered in a delivery system
comprising an adjuvant.
8. The method according to claim 2, wherein said at least one
fusion partner is an antigen expressed by bacteria within the
mycobacteria family other than a polypeptide selected from SEQ ID
NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,
19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 36,
37, 38, 39, 40, 41, 42, 43, 44, and 45.
9. The method according to claim 8, wherein said at least one
fusion partner is selected from the group consisting of ESAT-6,
ESAT-6-Ag85B, TB10.4, CFP10, RD1-ORF5, RD1-ORF2, Rv1036, MPB64,
MPT64, Ag85A, Ag85B (MPT59), MPB59, Ag85C, 19 kDa lipoprotein, and
MPT32.
10. The method according to claim 8, wherein the polypeptides are
recombinant or synthetic and are delivered in a delivery system
comprising an adjuvant.
11. The method according to claim 1, wherein said animal is a
mammal.
12. The method according to claim 11, wherein said mammal is a
human.
13. A method for inducing an immune response in an animal to
tuberculosis, comprising delivering one or more mycobacteria
polypeptides which are upregulated or expressed during the latent
stage of the mycobacteria infection which is characterized by
low-oxygen tension in the microenvironment of the mycobacteria and
(i) a pharmaceutically acceptable polymeric carrier bound to the
one or more polypeptides or (ii) a pharmaceutically acceptable
adjuvant, wherein said one or more polypeptides has the amino acid
sequence of SEQ ID NO: 33, wherein said one or more polypeptides is
fused to at least one mycobacteria fusion partner.
14. The method according to claim 13, where the polypeptides are
recombinant or synthetic and are delivered in a delivery system
comprising an adjuvant.
15. The method according to claim 13, wherein the fusion partner is
selected from SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,
14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,
31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, and 45.
16. The method according to claim 15, wherein the fusion partner is
an antigen expressed by bacteria within the mycobacteria family
other than a polypeptide selected from SEQ ID NO: 1, 2, 3, 4, 5, 6,
7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41,
42, 43, 44, and 45.
17. The method according to claim 16, wherein the fusion partner is
selected from the group consisting of ESAT-6, ESAT-6-Ag85B, TB10.4,
CFP10, RD1-ORF5, RD1-ORF2, Rv1036, MPB64, MPT64, Ag85A, Ag85B
(MPT59), MPB59, Ag85C, 19 kDa lipoprotein, and MPT32.
18. A method for inducing an immune response in an animal to latent
tuberculosis, comprising delivering a composition comprising one or
more mycobacteria polypeptides which are upregulated or expressed
during the latent stage of the mycobacteria infection, wherein one
polypeptide has the amino acid sequence of SEQ ID NO: 33.
19. The method according to claim 18, wherein the polypeptides are
recombinant or synthetic and are delivered in a delivery system
comprising an adjuvant.
20. The method according to claim 18, wherein the fusion partner is
selected from SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,
14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,
31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, and 45.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a division of U.S. patent application
Ser. No. 12/785,053, filed May 21, 2010, which is a continuation of
U.S. patent application Ser. No. 10/617,038, filed Jul. 11, 2003,
now abandoned, which claims the benefit of the priority of U.S.
Provisional Patent Application No. 60/401,725, filed Aug. 7, 2002,
now expired, and the priority of Danish Patent Patent Application
No. PA 2002 01098, filed Jul. 13, 2002, which applications are
incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] The present invention discloses a therapeutic vaccine
against latent or active tuberculosis infection caused by the
tuberculosis complex microorganisms (Mycobacterium tuberculosis, M.
bovis, M. africanum). The invention furthermore discloses a
multi-phase vaccine that can be administered either
prophylactically or therapeutically as well as a diagnostic reagent
for the detection of latent stages of tuberculosis.
[0003] Human tuberculosis caused by Mycobacterium tuberculosis (M.
tuberculosis) is a severe global health problem, responsible for
approx. 3 million deaths annually, according to the WHO. The
worldwide incidence of new tuberculosis (TB) cases had been falling
during the 1960s and 1970s but during recent decades this trend has
markedly changed in part due to the advent of AIDS and the
appearance of multidrug resistant strains of M. tuberculosis.
[0004] Organisms of the tuberculosis complex can cause a variety of
diseases, but the commonest route of invasion is by inhalation of
bacteria. This initiates an infection in the lung, which can
ultimately spread to other parts of the body. Normally, this
infection is restricted in growth by the immune system, so that the
majority of infected individuals show few signs apart from cough
and fever, which eventually abates. Approximately 30% of
individuals are unable to contain the infection and they will
develop primary disease, which in many cases will eventually prove
fatal. However, it is believed that even those individuals who
apparently control the infection remain infected, probably for the
rest of their life. Certainly, individuals who have been healthy
for years or even decades can suddenly develop tuberculosis, which
has proven to be caused by the same organism they were infected
with many years previously. M. tuberculosis and other organisms of
the TB complex are unique in that the mycobacteria can evade the
immune response and survive for long periods in a refractory
non-replicating or slowly-replicating stage. This is referred to as
latent TB and is at present a very significant global health
problem that is estimated to affect approximately 1/3 of the
world's population (Anon., 2001).
[0005] The course of a M. tuberculosis infection runs essentially
through 3 phases, as illustrated in FIG. 1. During the acute phase,
the bacteria proliferate in the organs, until the immune response
increases to the point at which it can control the infection,
whereupon the bacterial load peaks and starts declining. After
this, a latent phase is established where the bacterial load is
kept stable at a low level. In this phase M. tuberculosis goes from
active multiplication to dormancy, essentially becoming
non-replicating and remaining inside the granuloma. In some cases,
the infection goes to the reactivation phase, where the dormant
bacteria start replicating again. The full nature of the immune
response that controls latent infection and the factors that lead
to reactivation are largely unknown. However, there is some
evidence for a shift in the dominant cell types responsible. While
CD4 T cells are essential and sufficient for control of infection
during the acute phase, studies suggest that CD8 T cell responses
are more important in the latent phase. It is also likely that
changes in the antigen-specificity of the response occur, as the
bacterium modulates gene expression during its transition from
active replication to dormancy.
[0006] The only vaccine presently available for clinical use is
BCG, a vaccine whose efficacy remains a matter of controversy.
Although BCG consistently performs well in animal models of primary
infection, it has clearly failed to control the TB epidemic.
Consistent with that, BCG vaccination appears to provide protection
against pediatric TB (which is due to primary infection), while
offering little or no protection against adult disease (which is
often reactivation of latent infection acquired in childhood). It
has also been shown that vaccination of individuals who are
currently sensitized to mycobacteria or latently infected is
ineffective. Thus, current vaccination strategies, while effective
against primary disease, fail to activate immune responses that
efficiently control surviving dormant bacteria.
[0007] At this point no vaccine has been developed that confers
protection against reactivation whether given as a prophylactic
vaccine prior to infection or as a therapeutic vaccine given to
already latently infected individuals.
[0008] This makes the development of a new and improved vaccine
against TB an urgent matter, which has been given a very high
priority by the WHO. Many attempts to define protective
mycobacterial substances have been made, and different
investigators have reported increased resistance after experimental
vaccination. However, these efforts have almost exclusively focused
on the development of prophylactic vaccines for the prevention of
disease (Doherty, 2002), and such vaccines have not been
demonstrated to work if given in an immunotherapeutic fashion (J.
Turner et al., Infect and Immunity, 2000, pp. 1706-1709).
[0009] It has been suggested that the transition of M. tuberculosis
from primary infection to latency is accompanied by changes in gene
expression (see, for example, Honer zu Bentrup, 2001, which is
incorporated herein by reference). In vitro hypoxic culture
conditions, which mimic the conditions of low oxygen tension and
restricted nutrients found in the granuloma (the location of the
latent infection), have been used to analyze changes in gene
expression and a number of antigens have been found that are
induced or markedly upregulated under these conditions e.g. the 16
kDa antigen .alpha.-crystalline (Boon, 2001, Monahan, 2001,
Florczyk 2001, Sherman 2001, Manganelli, 2001, all of which are
incorporated herein by reference) and Rv0569 as described in
Rosenkrands, 2002, and which is described in WO0179274.
[0010] As noted in the references cited above, it is already known
that some genes are upregulated under conditions that mimic
latency. However, these are a limited subset of the total gene
expression during latent infection. Moreover, as one skilled in the
art will readily appreciate, expression of a gene is not sufficient
to make it a good vaccine candidate. The only way to determine if a
protein is recognized by the immune system during latent infection
with M. tuberculosis is to produce the given protein and test it in
an appropriate assay as described herein. Of the more than 200
hundred antigens known to be expressed during primary infection,
and tested as vaccines, less than a half dozen have demonstrated
significant potential. So far only one antigen has been shown to
have any potential as a therapeutic vaccine (Lowrie, 1999). However
this vaccine only worked if given as a DNA vaccine, an experimental
technique so far not approved for use in humans. Moreover, the
technique has proved controversial, with other groups claiming that
vaccination using this protocol induces either non-specific
protection or even worsens disease (J. Turner et al., Infect and
Immunity, 2000, pp. 1706-1709).
[0011] What are needed are therapeutic vaccines that treat latent
TB infection.
SUMMARY OF THE INVENTION
[0012] The present invention provides therapeutic vaccines based on
molecules that are induced or upregulated under the conditions of
low oxygen transmission and restricted nutrients found in the
granuloma (i.e., the location of latent TB infection). These
vaccines are therapeutic and contrast with prior art vaccines which
are designed to elicit protective immune responses prior to
infection (prophylactic vaccination) that are only effective
against primary infection. The immune responses elicited are
powerless against the latent stage of the disease, because the
bacteria have changed the antigens that they produce so that in
essence they have altered their appearance and the immune system
can no longer recognize them. However, latency is a dynamic
process, maintained by the immune response, as indicated by the
dramatic increase in the risk of reactivation of TB after HIV
infection or other events that compromise immunity. Therefore, an
effective vaccination strategy to protect infected individuals
(therapeutic vaccination) is possible, but only if it is directed
against those antigens expressed in the latent stage.
[0013] Further, the present invention provides a multiphase vaccine
that combines components with prophylactic and therapeutic
activity. In contrast, existing TB vaccines do not result in
sterilizing immunity but rather control the infection at a
subclinical level (thereby resulting in the subsequent
establishment of latent infection. After conventional prophylactic
vaccination, the evasion of the primary immune response and the
subsequent development of latent disease are probably at least in
part due to the change in the antigenic profile of the invading
bacteria. Thus, vaccinating with antigens associated with latent TB
prevents or reduces the establishment of latent infection and
therefore, a vaccine incorporating antigens expressed by the
bacteria both in the first logarithmic growth phase and during
latent disease improve long-term immunity when used as a
prophylactic vaccine. A multiphase vaccine of the invention will
also be efficient as a therapeutic vaccine thereby addressing the
problem that the majority of the population in the third world who
would receive a future TB vaccine could be already latently
infected.
[0014] For a number of years, a major effort has been put into the
identification of protective antigens for the development of novel
prophylactic vaccines against TB and today a few antigens with
demonstrated protective activity in prophylactic vaccines have been
identified (e.g. ESAT-6, the 38 kDa antigen, Ag85A and Ag85B). Such
molecules are useful components, which in combination with latency
associated antigens such as .alpha.-crystalline, form a multiphase
vaccine of the invention. Advantageously and in contrast to
antigens in the art, the antigens described in the invention are
incorporated in vaccines through the use of well-recognized
vaccination technology, as demonstrated in provided examples.
[0015] Finally, the immunodominant antigens identified in this
invention may be used as diagnostic reagents. Our group has
abundantly demonstrated that antigens expressed by mycobacteria
during the early stages of the infection, such as ESAT-6 (Early
Secretory Antigen Target-6) are recognized in individuals who are
in the process of developing primary TB, even though they are
healthy at the time of diagnosis (Doherty 2002). However, the large
numbers of contacts who are exposed, and almost certainly infected,
remain negative to this antigen (Doherty 2002). Since those
individuals latently infected remain healthy by making an immune
response against the latent bacteria, they must be making an immune
response to those antigens expressed by the latent bacteria. Thus,
the antigens of the invention may also be used to diagnose latent
infection and differentiate it from primary acute TB.
[0016] Other aspects and advantages of the invention will be
readily apparent to one of skill in the art.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIGS. 1A and 1B illustrate the results of testing in TB
vaccination models. A schematic time schedule of the models for
FIG. 1A, prophylactic vaccination and FIG. 1B, therapeutic
vaccination. Each square on the time axis represents one week.
Three prophylactic vaccinations two weeks apart are given 6 weeks
prior to an aerosol infection. The protective effect of the
vaccines is measured 6 weeks after infection, in the acute phase of
the infection. For analysis of therapeutic vaccinations a
reactivation model is established, where aerosol infected mice are
treated with anti-M tuberculosis drugs for 8 weeks from the peak of
infection (6 weeks after infection). This induces a latent
infection phase with a low bacterial load. Four to five weeks into
the latency phase three therapeutic vaccinations are given two
weeks apart and the protective effect of the vaccines is measured
as bacterial load in the reactivation phase, seven weeks after the
last immunization.
[0018] FIGS. 2A and 2B illustrate prophylactic and therapeutic
vaccine induced protection. C57Bl/6j mice were immunized 3 times
with a 2-week interval with recombinant ESAT6, BCG or recombinant
Rv2031c. In FIG. 2A, the immunization was given as a prophylactic
vaccine 6 weeks before the mice were given a M. tuberculosis
infection (approx. 250 bacilli) through the aerosol route with.
Bacterial numbers in the lung was enumerated 6 weeks post
infection. In FIG. 2B, the immunization was given as a therapeutic
vaccine after a latent infection had been established. Bacterial
numbers in the lung was enumerated 8 weeks after the last
immunization. The data represents the mean of 5 individual
mice.
[0019] FIG. 3 illustrates Rv2031c specific IFN-.gamma. responses.
Latent infected C57Bl/6j mice were either not immunized or
immunized with 3 .mu.g recombinant Rv2031 3 times with a two-week
interval. One and two weeks post immunization mice were bleed and
PBMCs isolated. The frequency of IFN-.gamma. producing cells
specific for either ESAT6 or Rv2031c was determined for both the
rRv2031c immunized and the unimmunized group. In an ELIspot plate
precoated with anti-IFN-.gamma. antibodies graded numbers of PBMCs
were incubated with either 2 .mu.g/ml rRv2031c or 2 .mu.g/ml
rESAT6. After 32 h the plate was washed and incubated with
biotinylated anti-INF-.gamma. antibodies followed by a
streptavidin-alkalinephosphatase incubation. The INF.gamma. spots,
representing individual IFN-.gamma. producing cells were visualized
using BCIP/NBT substrate. The results are shown as number Rv2031c
specific IFN-.gamma. producing cell (black bars) and number of
ESAT6 specific IFN-.gamma. producing cell (hatch bars) per 10.sup.6
PBMCs.
[0020] FIGS. 4A and 4B illustrate the results of epitope screening
of Rv2031c. PBMCs from rRv2031c immunized latently infected
C57Bl/6j mice were analyzed for recognition of 20' mer overlapping
peptides scanning through Rv2031c. In FIG. 4A, the peptides were
analyzed in pools of 3-4 peptides. PBMCs (2.times.10.sup.5) were
incubated for 72 h with the peptide pools at 5 .mu.g/ml per
peptide. Supernatant was harvested and secreted IFN-.gamma. was
quantitated by ELISA. In FIG. 4B, individual peptides of positive
pools were reanalyzed. PBMCs (2.times.10.sup.5) were incubated for
72 h with 1 .mu.g/ml of each peptide. Secreted IFN-.gamma. in the
supernatant was quantitated.
[0021] FIGS. 5A and 5B illustrate protection against reactivation
conferred by therapeutic vaccine given during latent infection.
Latent infected C57Bl/6j mice were immunized 3 times with or
without rRv2031c. Bacterial numbers in lung (FIG. 5A) and spleen
(FIG. 5B) was enumerated 8 weeks after the last immunization. The
data represents the mean of 8 individual mice.
[0022] FIGS. 6A and 6B illustrate Rv0569 specific IFN-.gamma.
responses. Latent infected C57Bl/6j mice were vaccinated with 3
.mu.g of either recombinant Rv0569 or recombinant ESAT6 in a
DDA/MPL adjuvant. The vaccines were given as 3 s.c. injections with
a two-week interval and the induced immune response were evaluated
7 weeks after the last vaccination. Isolated splenocytes
(2.times.10.sup.5) were incubated for 72 h with antigen at 1
.mu.g/ml. Supernatant was harvested and secreted IFN-.gamma. was
quantitated by ELISA using paired anti-murine IFN-.gamma.
antibodies (PharMingen) and recombinant IFN-.gamma. (PharMingen) as
standard. In FIG. 6A, Rv0569 specific response is measured in
Rv0569-vaccinated and un-vaccinated latently infected mice; in FIG.
6B, the ESAT6 specific response is measured in ESAT6-vaccinated and
un-vaccinated latently infected mice
[0023] FIGS. 7A and 7B illustrate therapeutic vaccine induced
protection against reactivation. Latently infected C57Bl/6j mice
were vaccinated once with BCG or 3 times with a 2-week interval
with either recombinant Rv0569 or recombinant ESAT6. Seven weeks
after the last vaccination the bacterial numbers was enumerated in
FIG. 7A, the lung and in FIG. 7B, the spleen of vaccinated and
un-vaccinated mice. The data represents the mean of Log CFU per
organ of 6-8 individual mice.
DETAILED DESCRIPTION OF THE INVENTION
[0024] The invention is related to preventing, treating and
detecting infections caused by species of the tuberculosis complex
(Mycobacterium tuberculosis, M. bovis, M. africanum) by the use of
a polypeptide comprising a M. tuberculosis antigen or an
immunogenic portion or other variant thereof, or by the use of a
DNA sequence encoding a M. tuberculosis antigen or an immunogenic
portion or other variant thereof. The invention discloses a new
therapeutic vaccine against tuberculosis comprising antigens
induced during the latent stage of TB-infection. It also discloses
a multiphase vaccine incorporating a combination of prophylactic
and therapeutic antigens as well as diagnostic reagents for the
detection of the latent stage of M. tuberculosis infection.
[0025] The present invention discloses the use of one or more
polypeptides, nucleic acids encoding these polypeptides or
fragments hereof, which polypeptides are expressed during the
latent stage of the mycobacteria infection, which stage is
characterized by low-oxygen tension in the microenvironment of the
mycobacteria, for a therapeutic vaccine against tuberculosis.
[0026] The polypeptides comprises one or more amino acid sequences
selected from [0027] (a) The sequences presented in Table 1. [0028]
(b) an immunogenic portion, e.g. a T-cell epitope, of any one of
the sequences in (a); and/or [0029] (c) an amino acid sequence
analogue having at least 70% sequence identity to any one of the
sequences in (a) or (b) and at the same time being immunogenic.
TABLE-US-00001 [0029] TABLE 1 Amino acid sequences of selected low
oxygen induced antigens Rv no. SEQ ID NO: Sequence Rv0569 91
MKAKVGDWLVIKGATIDQPDHRGLIIEVRSSDGSPPYVVRWLETDHVATV
IPGPDAVVVTAEEQNAADERAQHRFGAVQSAILHARGT Rv0079 1
VEPKRSRLVVCAPEPSHAREFPDVAVFSGGRANASQAERLARAVGRVLAD
RGVTGGARVRLTMANCADGPTLVQINLQVGDTPLRAQAATAGIDDLRPAL
IRLDRQIVRASAQWCPRPWPDRPRRRLTTPAEALVTRRKPVVLRRATPLQ
AIAAMDAMDYDVHLFTDAETGEDAVVYRAGPSGLRLARQHHVFPPGWSRC
RAPAGPPVPLIVNSRPTPVLTEAAAVDRAREHGLPFLETTDQATGRGQLL
YSRYDGNLGLITPTGDGVADGLA Rv0080 2
MSPGSRRASPQSAREVVELDRDEAMRLLASVDHGRVVFTRAALPAIRPVN
HLVVDGRVIGRTRLTAKVSVAVRSSADAGVVVAYEADDLDPRRRTGWSVV
VTGLATEVSDPEQVARYQRLLHPWVNMAMDTVVAIEPEIVTGIRIVADSR TP Rv0081 3
VESEPLYKLKAEFEKTLAHPARIRILELLVERDRSVGELLSSDVGLESSN
LSQQLGVLRRAGVVAARRDGNAMIYSIAAPDIAELLAVARKVLARVLSDR VAVLEDLRAGGSAT
Rv0363c 4 MPIATPEVYAEMLGQAKQNSYAFPAINCTSSETVNAAIKGFADAGSDGII
QFSTGGAEFGSGLGVKDMVTGAVALAEFTHVIAAKYPVNVALHTDHCPKD
KLDSYVRPLLAISAQRVSKGGNPLFQSHMWDGSAVPIDENLAIAQELLKA
AAAAKIILEIEIGVVGGEEDGVANEINEKLYTSPEDFEKTIEALGAGEHG
KYLLAATFGNVHGVYKPGNVKLRPDILAQGQQVAAAKLGLPADAKPFDFV
FHGGSGSLKSEIEEALRYGVVKMNVDTDTQYAFTRPIAGHMFTNYDGVLK
VDGEVGVKKVYDPRSYLKKAEASMSQRVVQACNDLHCAGKSLTH Rv0572c 5
MGEHAIKRHMRQRKPTKHPLAQKRGARILVFTDDPRRSVLIVPGCHLDSM
RREKNAYYFQDGNALVGMVVSGGTVEYDADDRTYVVQLTDGRHTTESSFE HSSPSRSPQSDDL
Rv0574c 6 VAGNPDVVTVLLGGDVMLGRGVDQILPHPGKPQLRERYMRDATGYVRLAE
RVNGRIPLPVDWRWPWGEALAVLENTATDVCLINLETTITADGEFADRKP
VCYRMHPDNVPALTALRPHVCALANNHILDFGYQGLTDTVAALAGAGIQS
VGAGADLLAARRSALVTVGHERRVIVGSVAAESSGVPESWAARRDRPGVW
LIRDPAQRDVADDVAAQVLADKRPGDIAIVSMHWGSNWGYATAPGDVAFA
HRLIDAGIDMVHGHSSHHPRPIEIYRGKPILYGCGDVVDDYEGIGGHESF
RSELRLLYLTVTDPASGNLISLQMLPLRVSRMRLQRASQTDTEWLRNTIE
RISRRFGIRVVTRPDNLLEVVPAANLTSKE Rv1264 7
VTDHVREADDANIDDLLGDLGGTARAERAKLVEWLLEQGITPDEIRATNP
PLLLATRHLVGDDGTYVSAREISENYGVDLELLQRVQRAVGLARVDDPDA
VVHMRADGEAAARAQRFVELGLNPDQVVLVVRVLAEGLSHAAEAMRYTAL
EAIMRPGATELDIAKGSQALVSQIVPLLGPMIQDMLFMQLRHMMETEAVN
AGERAAGKPLPGARQVTVAFADLVGFTQLGEVVSAEELGHLAGRLAGLAR
DLTAPPVWFIKTIGDAVMLVCPDPAPLLDTVLKLVEVVDTDNNFPRLRAG
VASGMAVSRAGDWFGSPVNVASRVTGVARPGAVLVADSVREALGDAPEAD
GFQWSFAGPRRLRGIRGDVRLFRVRRGATRTGSGGAAQDDDLAGSSP Rv1592c 8
MVEPGNLAGATGAEWIGRPPHEELQRKVRPLLPSDDPFYFPPAGYQHAVP
GTVLRSRDVELAFMGLIPQPVTATQLLYRTTNMYGNPEATVTTVIVPAEL
APGQTCPLLSYQCAIDAMSSRCFPSYALRRRAKALGSLTQMELLMISAAL
AEGWAVSVPDHEGPKGLWGSPYEPGYRVLDGIRAALNSERVGLSPATPIG
LWGYSGGGLASAWAAEACGEYAPDLDIVGAVLGSPVGDLGHTFRRLNGTL
LAGLPALVVAALQHSYPGLARVIKEHANDEGRQLLEQLTEMTTVDAVIRM
AGRDMGDFLDEPLEDILSTPEISHVFGDTKLGSAVPTPPVLIVQAVHDYL
IDVSDIDALADSYTAGGANVTYHRDLFSEHVSLHPLSAPMTLRWLTDRFA
GKPLTDHRVRTTWPTIFNPMTYAGMARLAVIAAKVITGRKLSRRPL Rv1733c 9
MIATTRDREGATMITFRLRLPCRTILRVFSRNPLVRGTDRLEAVVMLLAV
TVSLLTIPFAAAAGTAVQDSRSHVYAHQAQTRHPATATVIDHEGVIDSNT
TATSAPPRTKITVPARWVVNGIERSGEVNAKPGTKSGDRVGIWVDSAGQL
VDEPAPPARAIADAALAALGLWLSVAAVAGALLALTRAILIRVRNASWQH DIDSLFCTQR
Rv1734c 10 MTNVGDQGVDAVFGVIYPPQVALVSFGKPAQRVCAVDGAIHVMTTVLATL
PADHGCSDDHRGALFFLSINELTRCAAVTG Rv1736c 11
VTVTPRTGSRIEELLARSGRFFIPGEISADLRTVTRRGGRDGDVFYRDRW
SHDKVVRSTHGVNCTGSCSWKIYVKDDIITWETQETDYPSVGPDRPEYEP
RGCPRGAAFSWYTYSPTRVRHPYARGVLVEMYREAKARLGDPVAAWADIQ
ADPRRRRRYQRARGKGGLVRVSWAEATEMIAAAHVHTISTYGPDRVAGFS
PIPAMSMVSHAAGSREVELIGGVMTSFYDWYADLPVASPQVFGDQTDVPE
SGDWWDVVWQCASVLLTYPNSRQLGTAEELLAHIDGPAADLLGRTVSELR
RADPLTAATRYVDTFDLRGRATLYLTYWTAGDTRNRGREMLAFAQTYRST
DVAPPRGETPDFLPVVLEFAATVDPEAGRRLLSGYRVPTAALCNALTEAA
LPYAHTVAAVCRTGDMMGELFWTVVPYVTMTIVAVGSWWRYRYDKFGWTT
RSSQLYESRLLRIASPMFHFGILVVIVGHGIGLVIPQSWTQAAGLSEGAY
HVQAVVLGSIAGITTLAGVTLLIYRRRTRGPVFMATTVNDKVMYLVLVAA
IVAGLGATALGSGVVGEAYNYRETVSVWFRSVWVLQPRGDLMAEAPLYYQ
IHVLIGLALFALWPFTRLVHAFSAPIGYLFRPYIIYRSREELVLTRPRRR GW Rv1737c 12
MRGQAANLVLATWISVVNFWAWNLIGPLSTSYARDMSLSSAEASLLVATP
ILVGALGRIVTGPLTDRFGGRANLIAVTLASILPVLAVGVAATMGSYALL
VFFGLFLGVAGTIFAVGIPFANNWYQPARRGESTGVEGMGMVGTALSAFE
TPREVRWEGLFTTHAIVAAALASTAVVAMVVLRDAPYFRPNADPVLPRLK
AAARLPVTWEMSFLYAIVEGGEVAFSNYLPTYITTIYGESTVDAGARTAG
FALAAVLARPVGGWLSDRIAPRHVVLASLAGTALLAFAAALQPPPEVWSA
ATFITLAVCLGVGTGGVFAWVARRAPAASVGSVTGIVAAAGGLGGYFPPL
VMGATYDPVDNDYTVGLLLLVATALVACTYTALHAREPVSEEASR Rv1738c 13
MCGDQSDHVLQHWTVDISIDEHEGLTRAKARLRWREKELVGVGLARLNPA
DRNVPEIGDELSVARALSDLGKRMLKVSTHDIEAVTHQPARLLY Rv1739c 14
MIPTMTSAGWAPGVVQFREYQRRWLRGDVLAGLTVAAYLIPQAMAYATVA
GLPPAAGLWASIAPLAIYALLGSSRQLSIGPESATALMTAAVLAPMAAGD
LRRYAVLAATLGLLVGLICLLAGTARLGFLASLRSRPVLVGYMAGIALVM
ISSQLGTITGTSVEGNEFFSEVHSFATSVTRVHWPTFVLAMSVLALLTML
TRWAPRAPGPIIAVLAATMLVAVMSLDAKGIAIVGRIPSGLPTPGVPPVS
VEDLRALIIPAAGIAIVTFTDGVLTARAFAARRGQEVNANAELRAVGACN
IAAGLTHGFPVSSSSSRTALADVVGGRTQLYSLIALGLVVIVMVFASGLL
AMFPTAALGALVVYAALRLIDLSEFRRLARFRRSELMLALATTAAVLGLG
VFYGVLAAVALSILELLRRVAHPHDSVLGFVPGIAGMHDIDDYPQAKRVP
GLVVYRYDAPLCFANAEDFRRRALTVVDQDPGQVEWFVLNAESNVEVDLT
ALDALDQLRTELLRRGIVFAMARVKQDLRESLRAASLLDKIGEDHIFMTL PTAVQAFRRR
Rv1813c 15 MITNLRRRTAMAAAGLGAALGLGILLVPTVDAHLANGSMSEVMMSE
IAGLPIPPIIHYGAIAYAPSGASGKAWHQRTPARAEQVALEKCGDK
TCKVVSRFTRCGAVAYNGSKYQGGTGLTRRAAEDDAVNRLEGGRIV NWACN Rv1997c 16
LSASVSATTAHHGLPAHEVVLLLESDPYHGLSDGEAAQRLERFGPNTLAV
VTRASLLARILRQFHHPLIYVLLVAGTITAGLKEFVDAAVIFGVVVINAI
VGFIQESKAEAALQGLRSMVHTHAKVVREGHEHTMPSEELVPGDLVLLAA
GDKVPADLRLVRQTGLSVNESALTGESTPVHKDEVALPEGTPVADRRNIA
YSGTLVTAGHGAGIVVATGAETELGEIHRLVGAAEVVATPLTAKLAWFSK
FLTTATLGLAALTFGVGLLRRQDAVETFTAAIALAVGAIPEGLPTAVTIT
LAIGMARMAKRRAVIRRLPAVETLGSTTVICADKTGTLTENQMTVQSIWT
PHGEIRATGTGYAPDVLLCDTDDAPVPVNANAALRWSLLAGACSNDAALV
RDGTRWQIVGDPTEGAMLVVAAKAGFNPERLATTLPQVAAIPFSSERQYM
ATLHRDGTDHVVLAKGAVERMLDLCGTEMGADGALRPLDRATVLRATEML
TSRGLRVLATGMGAGAGTPDDFDENVIPGSLALTGLQAMSDPPRAAAASA
VAACHSAGIAVKMITGDHAGTATAIATEVGLLDNTEPAAGSVLTGAELAA
LSADQYPEAVDTASVFARVSPEQKLRLVQALQARGHVVAMTGDGVNDAPA
LRQANIGVAMGRGGTEVAKDAADMVLTDDDFATIEAAVEEGRGVFDNLTK
FITWTLPTNLGEGLVILAAIAVGVALPILPTQILWINMTTAIALGLMLAF
EPKEAGIMTRPPRDPDQPLLTGWLVRRTLLVSTLLVASAWWLFAWELDNG
AGLHEARTAALNLFVVVEAFYLFSCRSLTRSAWRLGMFANRWIILGVSAQ
AIAQFATTYLPAMNMVFDTAPIDIGVWVRIFAVATAITIVVATDTLLPRI RAQPP Rv1998c 17
MSFHDLHHQGVPFVLPNAWDVPSALAYLAEGFTAIGTTSFGVSSSGGHPD
GHRATRGANIALAAALAPLQCYVSVDIEDGYSDEPDAIADYVAQLSTAGI
NIEDSSAEKLIDPALAAAKIVAIKQRNPEVFVNARVDTYWLRQHADTTST
IQRALRYVDAGADGVFVPLANDPDELAELTRNIPCPVNTLPVPGLTIADL
GELGVARVSTGSVPYSAGLYAAAHAARAVSDGEQLPRSVPYAELQARLVD YENRTSTT Rv2003c
18 VVKRSRATRLSPSIWSGWESPQCRSIRARLLLPRGRSRPPNADCCWNQLA
VTPDTRMPASSAAGRDAAAYDAWYDSPTGRPILATEVAALRPLIEVFAQP
RLEIGVGTGRFADLLGVREGLDPSRDALMFARRRGVLVANAVGEAVPFVS
RHFGAVLMAFTLCFVTDPAAIFRETRRLLADGGGLVIGELPRGTPWADLY
ALRAARGQPGYRDARFYTAAELEQLLADSGFRVIARRCTLHQPPGLARYD
IEAAHDGIQAGAGFVAISAVDQAHEPKDDHPLESE Rv2005c 19
MSKPRKQHGVVVGVDGSLESDAAACWGATDAAMRNIPLTVVHVVNADVAT
WPPMPYPETWGVWQEDEGRQIVANAVKLAKEAVGADRKLSVKSELVFSTP
VPTMVEISNEAEMVVLGSSGRGALARGLLGSVSSSLVRRAGCPVAVIHSD
DAVIPDPQHAPVLVGIDGSPVSELATAVAFDEASRRGVELIAVHAWSDVE
VVELPGLDFSAVQQEAELSLAERLAGWQERYPDVPVSRVVVCDRPARKLV
QKSASAQLVVVGSHGRGGLTGMLLGSVSNAVLHAARVPVIVARQS Rv2007c 20
VTYVIGSECVDVMDKSCVQECPVDCIYEGARMLYINPDECVDCGACKPAC
RVEAIYWEGDLPDDQHQHLGDNAAEFHQVLPGRVAPLGSPGGAAAVGPIG VDTPLVAAIPVECP
Rv2028c 21 MNQSHKPPSIVVGIDGSKPAVQAALWAVDEAASRDIPLRLLYAIEPDDPG
YAAHGAAARKLAAAENAVRYAFTAVEAADRPVKVEVEITQERPVTSLIRA
SAAAALVCVGAIGVHHFRPERVGSTAAALALSAQCPVAIVRPHRVPIGRD
AAWIVVEADGSSDIGVLLGAVMAEARLRDSPVRVVTCRQSGVGDTGDDVR
ASLDRWLARWQPRYPDVRVQSAAVHGELLDYLAGLGRSVHMVVLSASDQE
HVEQLVGAPGNAVLQEAGCTLLVVGQQYL Rv2029c 22
MTEPAAWDEGKPRIITLTMNPALDITTSVDVVRPTEKMRCGAPRYDPGGG
GINVARIVHVLGGCSTALFPAGGSTGSLLMALLGDAGVPFRVIPIAASTR
ESFTVNESRTAKQYRFVLPGPSLTVAEQEQCLDELRGAAASAAFVVASGS
LPPGVAADYYQRVADICRRSSTPLILDTSGGGLQHISSGVFLLKASVREL
RECVGSELLTEPEQLAAAHELIDRGRAEVVVVSLGSQGALLATRHASHRF
SSIPMTAVSGVGAGDAMVAAITVGLSRGWSLIKSVRLGNAAGAAMLLTPG
TAACNRDDVERFFELAAEPTEVGQDQYVWHPIVNPEASP Rv2030c 23
VLMTAAADVTRRSPRRVFRDRREAGRVLAELLAAYRDQPDVIVLGLARGG
LPVAWEVAAALHAPLDAFVVRKLGAPGHDEFAVGALASGGRVVVNDDVVR
GLRITPQQLRDIAEREGRELLRRESAYRGERPPTDITGKTVIVVDDGLAT
GASMFAAVQALRDAQPAQIVIAVPAAPESTCREFAGLVDDVVCATMPTPF
LAVGESFWDFRQVTDEEVRRLLATPTAGPSLRRPAASTAADVLRRVAIDA
PGGVPTHEVLAELVGDARIVLIGESSHGTHEFYQARAAMTQWLIEEKGFG
AVAAEADWPDAYRVNRYVRGLGEDTNADEALSGFEREPAWMWRNTVVRDF
VEWLRTRNQRYESGALRQAGFYGLDLYSLHRSIQEVISYLDKVDPRAAAR
ARARYACFDHACADDGQAYGFAAAFGAGPSCEREAVEQLVDVQRNALAYA
RQDGLLAEDELFYAQQNAQTVRDAEVYYRAMFSGRVTSWNLRDQHMAQTL
GSLLTHLDRHLDAPPARIVVWAHNSHVGDARATEVWADGQLTLGQIVRER
YGDESRSIGESTYTGTVTAASEWGGIAQRKAVRPALHGSVEELFHQTADS
FLVSARLSRDAEAPLDVVRLGRAIGVVYLPATERQSHYLHVRPADQFDAM
IHIDQTRALEPLEVTSRWIAGENPETYPTGL Rv2031c 24
MATTLPVQRHPRSLFPEESELFAAFPSFAGLRPTFDTRLMRLEDEMKEGR
YEVRAELPGVDPDKDVDIMVRDGQLTIKAERTEQKDFDGRSEFAYGSFVR
TVSLPVGADEDDIKATYDKGILTVSVAVSEGKPTEKHIQIRSTN Rv2032 25
MPDTMVTTDVIKSAVQLACRAPSLHNSQPWRWIAEDHTVALFLDKDRVLY
ATDHSGREALLGCGAVLDHFRVAMAAAGTTANVERFPNPNDPLHLASIDF
SPADFVTEGHRLRADAILLRRTDRLPFAEPPDWDLVESQLRTTVTADTVR
IDVIADDMRPELAAASKLTESLRLYDSSYHAELFWWTGAFETSEGIPHSS
LVSAAESDRVTFGRDEPVVANTDRRPEFGHDRSKVLVLSTYDNERASLLR
CGEMLSAVLLDATMAGLATCTLTHITELHASRDLVAALIGQPATPQALVR
VGLAPEMEEPPPATPRRPIDEVFHVRAKDHR Rv2428 26
MPLLTIGDQFPAYQLTALIGGDLSKVDAKQPGDYFTTITSDEHPGKWRVV
FEWPKDFTEVCPTEIAAFSKLNDEFEDRDAQILGVSIDSEFAHFQWRAQH
NDLKTLPFPMLSDIKRELSQAAGVLNADGVADRVTFIVDPNNEIQFVSAT
AGSVGRNVDEVLRVLDALQSDELCACNWRKGDPTLDAGELLKASA Rv2624c 27
MSGRGEPTMKTIIVGIDGSHAAITAALWGVDEAISRAVPLRLVSVIKPTH
PSPDDYDRDLAHAERSLREAQSAVEAAGKLVKIETDIPRGPAGPVLVEAS
RDAEMICVGSVGIGRYASSILGSTATELAEKAHCPVAVMRSKVDQPASDI
NWIVVRMTDAPDNEAVLEYAAREAKLRQAPILALGGRPEELREIPDGEFE
RRVQDWHHRHPDVRVYPITTHTGIARFLADHDERVQLAVIGGGEAGQLAR
LVGPSGHPVFRHAECSVLVVRR Rv2625c 28
MRDAIPLGRIAGFVVNVHWSVLVILWLFTWSLATMLPGTVGGYPAVVYWL
LGAGGAVMLLASLLAHELAHAVVARRAGVSVESVTLWLFGGVTALGGEAK
TPKAAFRIAFAGPATSLALSATFGALAITLAGVRTPAIVISVAWWLATVN
LLLGLFNLLPGAPLDGGRLVRAYLWRRHGDSVRAGIGAARAGRVVALVLI
ALGLAEFVAGGLVGGVWLAFIGWFIFAAAREEETRISTQQLFAGVRVADA
MTAQPHTAPGWINVEDFIQRYVLGERHSAYPVADRDGSITGLVALRQLRD
VAPSRRSTTSVGDIALPLHSVPTARPQEPLTALLERMAPLGPRSRALVTE
GSAVVGIVTPSDVARLIDVYRLAQPEPTFTTSPQDADRFSDAG Rv2727c 29
MASSASGDTHERSAFRLSPPVLSGAMGPFMHTGLYVAQSWRDYLGQQPDK
LPTARPTIALAAQAFRDEIVLLGLKARRPVSNHRVFERISQEVAAGLEFY
GNRRWLEKPSGFFAQPPPLTEVAVRKVKDRRRSFYRIFEDSGFTPHPGEP
GSQRWLSYTANNREYALLLRHPEPRPWLVCVHGTEMGRAPLDLAVFRAWK
LHDELGLNIVMPVLPMHGPRGQGLPKGAVFPGEDVLDDVHGTAQAVWDIR
RLLSWIRSQEEESLIGLNGLSLGGYIASLVASLEEGLACAILGVPVADLI
ELLGRHCGLRHKDPRRHTVKMAEPIGRMISPLSLTPLVPMPGRFIYAGIA
DRLVHPREQVTRLWEHWGKPEIVWYPGGHTGFFQSRPVRRFVQAALEQSG LLDAPRTQRDRSA
Rv2628 30 MSTQRPRHSGIRAVGPYAWAGRCGRIGRWGVHQEAMMNLAIWHPRKVQSA
TIYQVTDRSHDGRTARVPGDEITSTVSGWLSELGTQSPLADELARAVRIG
DWPAAYAIGEHLSVEIAVAV Rv2629 31
MRSERLRWLVAAEGPFASVYFDDSHDTLDAVERREATWRDVRKHLESRDA
KQELIDSLEEAVRDSRPAVGQRGRALIATGEQVLVNEHLIGPPPATVIRL
SDYPYVVPLIDLEMRRPTYVFAAVDHTGADVKLYQGATISSTKIDGVGYP
VHKPVTAGWNGYGDFQHTTEEAIRMNCRAVADHLTRLVDAADPEVVFVSG
EVRSRTDLLSTLPQRVAVRVSQLHAGPRKSALDEEEIWDLTSAEFTRRRY
AEITNVAQQFEAEIGRGSGLAAQGLAEVCAALRDGDVDTLIVGELGEATV
VTGKARTTVARDADMLSELGEPVDRVARADEALPFAAIAVGAALVRDDNR
IAPLDGVGALLRYAATNRLGSHRS Rv2630 32
MLHRDDHINPPRPRGLDVPCARLRATNPLRALARCVQAGKPGTSSGHRSV
PHTADLRIEAWAPTRDGCIRQAVLGTVESFLDLESAHAVHTRLRRLTADR
DDDLLVAVLEEVIYLLDTVGETPVDLRLRDVDGGVDVTFATTDASTLVQV
GAVPKAVSLNELRFSQGRHGWRCAVTLDV Rv2659c 33
VTQTGKRQRRKFGRIRQFNSGRWQASYTGPDGRVYIAPKTFNAKIDAEAW
LTDRRREIDRQLWSPASGQEDRPGAPFGEYAEGWLKQRGIKDRTRAHYRK
LLDNHILATFADTDLRDITPAAVRRWYATTAVGTPTMRAHSYSLLRAIMQ
TALADDLIDSNPCRISGASTARRVHKIRPATLDELETITKAMPDPYQAFV
LMAAWLAMRYGELTELRRKDIDLHGEVARVRRAVVRVGEGFKVTTPKSDA
GVRDISIPPHLIPAIEDHLHKHVNPGRESLLFPSVNDPNRHLAPSALYRM
FYKARKAAGRPDLRVHDLRHSGAVLAASTGATLAELMQRLGHSTAGAALR
YQHAAKGRDREIAALLSKLAENQEM Rv2780 34
MRVGIPTETKNNEFRVAITPAGVAELTRRGHEVLIQAGAGEGSAITDADF
KAAGAQLVGTADQVWADADLLLKVKEPIAAEYGRLRHGQILFTFLHLAAS
RACTDALLDSGTTSIAYETVQTADGALPLLAPMSEVAGRLAAQVGAYHLM
RTQGGRGVLMGGVPGVEPADVVVIGAGTAGYNAARIANGMGATVTVLDIN
IDKLRQLDAEFCGRIHTRYSSAYELEGAVKRADLVIGAVLVPGAKAPKLV
SNSLVAHMKPGAVLVDIAIDQGGCFEGSRPTTYDHPTFAVHDTLFYCVAN
MPASVPKTSTYALTNATMPYVLELADHGWRAACRSNPALAKGLSTHEGAL
LSERVATDLGVPFTEPASVLA Rv3126c 35
MVIRFDQIGSLVLSMKSLASLSFQRCLRENSSLVAALDRLDAAVDELSAL
SFDALTTPERDRARRDRDHHPWSRSRSQLSPRMAHGAVHQCQWPKAVWAV IDNP Rv3127 36
VLKNAVLLACRAPSVHNSQPWRWVAESGSEHTTVHLFVNRHRTVPATDHS
GRQAIISCGAVLDHLRIAMTAAHWQANITRFPQPNQPDQLATVEFSPIDH
VTAGQRNRAQAILQRRTDRLPFDSPMYWHLFEPALRDAVDKDVAMLDVVS
DDQRTRLVVASQLSEVLRRDDPYYHAELEWWTSPFVLAHGVPPDTLASDA
ERLRVDLGRDFPVRSYQNRRAELADDRSKVLVLSTPSDTRADALRCGEVL
STILLECTMAGMATCTLTHLIESSDSRDIVRGLTRQRGEPQALIRVGIAP
PLAAVPAPTPRRPLDSVLQIRQTPEKGRNASDRNARETGWFSPP Rv3128c 37
VWSASGGQCGKYLAASMVLQLDGLERHGVLEFGRDRYGPEVREELLAMSA
ASIDRYLKTAKAKDQISGVSTTKPSPLLRNSIKVRRAGDEVEAEPGFFEG
DTVAHCGPTLKGEFAHTLNLTDVHIGWVFTRTVRNNARTHILAGLKASVT
EIPHGITGLDFDNGTVELNKPVISWAGDNGIYFTRFRPYKKNH*ATIESK
NNHLVRKYAFYYRYDTAEERAVLNRMWKLVNDRLNYLTPTIKPIGYASSA
DGRRRRLYDAPQTPLDRPLAARVLSAAQQADLITYRDSLNPAQIGRKIAD
LQNRLLILAKEKTEQLYLANIPTALPDIHKGILIKAG Rv3129 38
VVQGRTVLFRTAEGAKLFSAVAKCAVAFEADDHNVAEGWSVIVKVRAQVL
TTDAGVREAERAQLLPWTATLKRHCVRVIPWEITGRHFREGPEPDRSQTF ACEASSHNQR
Rv3130c 39 MNHLTTLDAGFLKAEDVDRHVSLAIGALAVIEGPAPDQEAFLSSLAQRLR
PCTRFGQRLRLRPFDLGAPKWVDDPDFDLGRHVWRIALPRPGNEDQLFEL
IADLMARRLDRGRPLWEVWVIEGLADSKWAILTKLHHCMADGIAATHLLA
GLSDESMSDSFASNIHTTMQSQSASVRRGGFRVNPSEALTASTAVMAGIV
RAAKGASEIAAGVLSPAASSLNGPISDLRRYSAAKVPLADVEQVCRKFDV
TINDVALAAITESYRNVLIQRGERPREDSLRTLVPVSTRSNSALSKTDNR
VSLMLPNLPVDQENPLQRLRIVHSRLTRAKAGGQRQFGNTLMAIANRLPF
PMTAWAVGLLMRLPQRGVVTVATNVPGPRRPLQIMGRRVLDLYPVSPIAM
QLRTSVAMLSYADDLYFGILADYDVVADAGQLARGIEDAVARLVAISKRR KVTRRRGALSLVV
Rv3131 40 MNTHFPDAETVRTVLTLAVRAPSIHNTQPWRWRVCPTSLELFSRRDMQLR
STDPDGRELILSCGVALHHCVVALASLGWQAKVNRFPDPKDRCHLATIGV
QPLVPDQADVALAAAIPRRRTDRRAYSCWPVPGGDIALMAARAARGGVML
RQVSALDRMKAIVAQAVLDHVTDEEYLRELTIWSGRYGSVAGVPARNEPP
SDPSAPIPGRLFAGPGLSQPSDVLPADDGAAILALGTETDDRLARLRAGE
AASIVLLTATAMGLACCPITEPLETAKTRDAVRAEVEGAGGYPQMLLRVG
WAPINADPLPPTPRRELSQVVEWPEELLRQRC Rv3132 41
MTTGGLVDENDGAAMRPLRHTLSQLRLHELLVEVQDRVEQIVEGRDRLDG
LVEAMLVVTAGLDLEATLRAIVHSATSLVDARYGAMEVHDRQHRVLHEVY
EGIDEETVRRIGHLPKGLGVIGLLIEDPKPLRLDDVSAHPASIGFPPYHP
PMRTFLGVPVRVRDESEGTLYLTDKTNGQPFSDDDEVLVQALAAAAGIAV
ANARLYQQAKARQSWIEATRDTATELLSGTEPATVFRLVAAEALKLTAAD
AALVAVPVDEDMPAADVGELLVIETVGSAVASIVGRTIPVAGAVLREVFV
NGIPRRVDRVDLEGLDELADAGPALLLPLRARGTVAGVVVVLSQGGPGAF
TDEQLEMMAAFADQAALAWQLATSQRRMRELDVLTDRDRIARDLHDHVIQ
RLFATGLALQGAVPHERNPEVQQRLSDVVDDLQDVIQEIRTTIYDLHGAS
QGITRLRQRIDAAVAQFADSGLRTSVQFVGPLSVVDSALADQAEAVVREA
VSNAVRHAKASTLTVRVKVDDDLCIEVTDNGRGLPDEFTGSGLTNLRQRA
EQAGGEFTLASVPGASGTVLRWSAPLSQ Rv3134c 42
MSDPRPARAVVVGIDGSRAATHAALWAVDEAVNRDIPLRLVYVIDPSQLS
AAGEGGGQSAARAALHDASRKVEATGQPVKIETEVLCGRPLTKLMQESRS
AAMLCVGSVGLDHVRGRRGSVAATLAGSALCPVAVIHPSPAEPATTSQVS
AVVAEVDNGVVLRHAFEEARLRGVPLRAVAVHAAETPDDVEQGSRLAHVH
LSRRLAHWTRLYPEVRVDRAIAGGSACRHLAANAKPGQLFVADSHSAHEL
CGAYQPGCAVLTVRSANL Rv3841 43
MTEYEGPKTKFHALMQEQIHNEFTAAQQYVAIAVYFDSEDLPQLAKHFYS
QAVEERNHAMMLVQHLLDRDLRVEIPGVDTVRNQFDRPREALALALDQER
TVTDQVGRLTAVARDEGDFLGEQFMQWFLQEQIEEVALMATLVRVADRAG
ANLFELENFVAREVDVAPAASGAPHAAGGRL Rv3842c 44
MTWADEVLAGHPFVVAHRGASAARPEHTLAAYDLALKEGADGVECDVRLT
RDGHLVCVHDRRLDRTSTGAGLVSTMTLAQLRELEYGAWHDSWRPDGSHG
DTSLLTLDALVSLVLDWHRPVKIFVETKHPVRYGSLVENKLLALLHRFGI
AAPASADRSRAVVMSFSAAAVWRIRRAAPLLPTVLLGKTPRYLTSSAATA
VGATAVGPSLPALKEYPQLVDRSAAQGRAVYCWNVDEYEDIDFCREVGVA
WIGTHHPGRTKAWLEDGRANGTTR Rv3908 45
VSDGEQAKSRRRRGRRRGRRAAATAENHMDAQPAGDATPTPATAKRSRSR
SPRRGSTRMRTVHETSAGGLVIDGIDGPRDAQVAALIGRVDRRGRLLWSL
PKGHIELGETAEQTAIREVAEETGIRGSVLAALGRIDYWFVTDGRRVHKT
VHHYLMRFLGGELSDEDLEVAEVAWVPIRELPSRLAYADERRLAEVADEL
IDKLQSDGPAALPPLPPSSPRRRPQTHSRARHADDSAPGQHNGPGPGP
TABLE-US-00002 TABLE 2 DNA sequences of selected low oxygen induced
antigens Rv no. SEQ ID NO: Sequence Rv0079c 46
gtggaaccgaaacgcagtcgcctcgtcgtatgtgcacccgagccatcgca
cgcgcgggaattcccggatgtcgccgtattctccggcggccgggctaacg
catcccaggccgaacggttggctcgtgccgtgggtcgcgtgttggccgat
cggggcgtcaccgggggtgctcgggtgcggctgaccatggcgaactgcgc
cgatgggccgacgctggtgcagataaacctgcaggtaggtgacaccccat
taagggcgcaggccgccaccgcgggcatcgatgatctgcgacccgcactg
atcagactggatcgacagatcgtgcgggcgtcggcacagtggtgcccccg
gccttggccggatcggccccgccggcgattgaccacgccggccgaggcgc
tagtcacccgccgcaaaccggtcgtgctaaggcgcgcaaccccgttgcag
gcgattgccgctatggacgccatggactacgacgtgcatttgttcaccga
cgccgagacgggggaggacgctgtggtctatcgggctggaccgtcggggc
tgcggctggcccgccagcaccacgtatttcccccaggatggtcacgttgt
cgcgccccagccgggccgccggtgccgctgattgtgaattcgcgtccgac
accggttctcacggaggccgccgcggtggaccgggcgcgcgaacatggac
tgccattcctgtttttcaccgaccaggccaccggccgcggccagctgctc
tactcccgctacgacggcaacctcgggttgatcaccccgaccggtgacgg
cgttgccgacggtctggca Rv0080 47
atgagcccgggctcgcggcgcgccagcccgcaaagcgcccgggaggtggt
cgagctcgaccgtgacgaggcgatgcggttgctggccagcgttgaccatg
ggcgtgtggtgttcacccgcgcggcgctgccggcgatccgtccagtcaat
cacctcgtggtcgacggtcgggtgatcgggcgcacccgcctgacggccaa
ggtgtccgttgcggtgcgatcgagcgccgatgccggtgtcgtggtcgcct
acgaagccgacgaccttgatccgcggcgtcggacggggtggagtgtggtg
gtgacgggactggcgaccgaggtcagcgatcccgagcaggttgcccgcta
ccagcggctgctacacccgtgggtgaacatggcgatggacaccgtggtcg
cgatcgaacccgagatcgtcaccggcatccgcatcgttgctgactcgcgt acgccg Rv0081 48
gtggagtccgaaccgctgtacaagctcaaggcggagttcttcaaaaccct
tgcgcatccggcgcggatcaggattttggagctgctggtcgagcgggacc
gttcggtcggtgagttgctgtcctcggacgtcggcctggagtcgtcgaac
ctgtcccagcagctgggtgtgctacgccgggcgggtgttgtcgcggcacg
tcgtgacggcaacgcgatgatctattcgattgccgcacccgatatcgccg
agctgctggcggtggcacgcaaggtgctggccagggtgctcagcgaccgg
gtggcggtgctagaggacctccgcgccggcggctcggccacg Rv0363c 49
atgcctatcgcaacgcccgaggtctacgcggagatgctcggtcaggccaa
acaaaactcgtacgctttcccggctatcaactgcacctcctcggaaaccg
tcaacgccgcgatcaaaggtttcgccgacgccggcagtgacggaatcatc
cagttctcgaccggtggcgcagaattcggctccggcctcggggtcaaaga
catggtgaccggtgcggtcgccttggcggagttcacccacgttatcgcgg
ccaagtacccggtcaacgtggcgctgcacaccgaccactgccccaaggac
aagttggacagctatgtccggcccttgctggcgatctcggcgcaacgcgt
gagcaaaggtggcaatcctttgttccagtcgcacatgtgggacggctcgg
cagtgccaatcgatgagaacctggccatcgcccaggagctgctcaaggcg
gcggcggccgccaagatcattctggagatcgagatcggcgtcgtcggcgg
cgaagaggacggcgtggcgaacgagatcaacgagaagctgtacaccagcc
cggaggacttcgagaaaaccatcgaggcgctgggcgccggtgagcacggc
aaatacctgctggccgcgacgttcggcaacgtgcatggcgtctacaagcc
cggcaacgtcaagcttcgccccgacatccttgcgcaagggcaacaggtgg
cggcggccaagctcggactgccggccgacgccaagccgttcgacttcgtg
ttccacggcggctcgggttcgcttaagtcggagatcgaggaggcgctgcg
ctacggcgtggtgaagatgaacgtcgacaccgacacccagtacgcgttca
cccgcccgatcgccggtcacatgttcaccaactacgacggagtgctcaag
gtcgatggcgaggtgggtgtcaagaaggtctacgacccgcgcagctacct
caagaaggccgaagcttcgatgagccagcgggtcgttcaggcgtgcaatg
acctgcactgcgccggaaagtccctaacccac Rv0572c 50
atgggtgagcacgccatcaagcggcacatgcggcaacggaagcctacgaa
gcatcccctagcccagaaacggggcgcgcggattctggtcttcaccgacg
atccccgcaggagcgtcctcatagtgcccggttgccacctggattccatg
cgccgagaaaagaacgcgtactacttccaggacggcaatgcgttggttgg
gatggttgtctcgggcggcacggttgagtacgacgccgacgaccgcacat
atgtcgtgcagctcaccgacggaaggcacaccactgagtcatctttcgaa
cactcatcgccgagtcgatcacctcaatccgatgaccta Rv0574c 51
gtggctggcaatcctgatgtggtgacggtgctgctgggcggtgacgtcat
gctcggccgtggcgtcgatcagatcctgcctcatcccggcaaaccgcaat
tgcgcgaacggtatatgcgggatgcgaccggctatgttcgcctggccgag
cgggtgaacgggcgcattccgctccccgtggattggcgctggccctgggg
cgaggcgttggcggtccttgagaacaccgcgaccgacgtctgtttgatca
atctggagacgacgatcaccgccgacggtgaattcgccgaccgcaaaccg
gtctgctaccggatgcacccggataacgtgccggcgctgacggcattgcg
gccgcacgtgtgcgcgctggccaacaaccacattctcgatttcggctacc
aggggctgaccgatacggtcgcggctctcgccggtgcggggatccagagt
gtcggggcgggagccgatttgctcgccgctcgccgctcggcgctagtcac
ggttggccatgaacgccgggtgatcgtcggctcggtagcggcggaatcca
gcggcgtccccgaatcctgggccgcccgccgcgaccggcccggagtgtgg
ttgatccgggatccggcgcaacgcgacgtcgccgacgatgtggcggcaca
ggtgctggcggacaaacgccccggcgatatcgccatagtctcgatgcatt
ggggatccaattggggctatgcgaccgcacccggcgacgtcgcgttcgcg
caccgactgatcgacgccggcatcgacatggtccacggacattcctcgca
ccatccgcggccaatcgagatatatcgcggtaaaccgatcctgtacggat
gcggtgacgtcgttgacgactacgaaggcatcggcgggcacgagtcgttc
cgcagtgaactgcgactgctgtatctgaccgtcaccgatcccgccagcgg
gaacctgatctcgctgcagatgcttccactgcgagtgtcgcggatgcgcc
tacagcgtgcctcccagaccgacaccgaatggctccgcaacaccattgag
cgcatcagccgccggttcgggattcgagtcgtgactcgacccgacaacct
gctggaggtcgttcccgctgccaacctaacgagcaaggag Rv1264 52
gtgacagaccacgtgcgcgaggcggacgacgcgaacatcgacgatctgtt
gggcgacctgggcggtaccgcgcgcgccgagcgtgcgaagcttgtcgagt
ggttgctcgagcagggcatcacccccgacgagattcgggcgaccaacccg
ccgttgctgctggccacccgccacctcgtcggcgacgacggcacctacgt
atccgcaagggagattagcgagaactatggcgttgacctcgagctgctgc
agcgggtgcagcgcgctgtcggtctggccagagtggatgatcctgacgcg
gtggtgcacatgcgtgccgacggtgaggcggccgcacgcgcacagcggtt
cgttgagctggggctgaatcccgaccaagtcgtgctggtcgtgcgtgtgc
tcgccgagggcttgtcacacgccgccgaggccatgcgctacaccgcgctg
gaggccattatgcggccgggggctaccgagttggacatcgcgaaggggtc
gcaggcgctggtgagccagatcgtgccgctgctggggccgatgatccagg
acatgctgttcatgcagctgcggcacatgatggagacggaggccgtcaac
gccggagagcgtgcggccggcaagccgctaccgggagcgcgacaggtcac
cgttgccttcgccgacctggtcggtttcacccagctaggcgaagtggtgt
cggccgaagagctagggcacctcgccgggcggctggccggcctcgcgcgt
gacctgaccgctccgccggtgtggttcattaagacgatcggcgacgcggt
catgttggtctgtcctgatccggcgccattgctggacaccgtgctgaagc
tggtcgaggtcgtcgacaccgacaacaactttccccggctgcgagccggc
gtcgcctccgggatggcggttagccgggccggcgactggttcggcagccc
ggtcaacgtggcaagccgggtgaccggggtggcgcgcccgggtgccgtgc
tggtcgcggattcggtgcgggaggcccttggtgatgcccccgaagccgac
ggatttcagtggtccttcgccggcccccgtcgcctcaggggaatccgggg
tgacgtcaggctttttcgagtccggcgaggggccactcgcaccggctccg
gcggcgcggcccaagacgacgatttggccggctcgtcaccg Rv1592c 53
atggtagagcccggcaatttggcaggcgcgaccggcgccgaatggatcgg
ccggccaccgcacgaggaattgcagcgcaaagtgcgcccgctgctgccat
ccgacgatccgttctacttcccacctgccggctaccagcatgccgtgccc
ggaacggtgttgcgctcgcgcgatgtcgaactggcgtttatgggcttgat
tccgcagcccgtcaccgctacccagctgctgtaccggaccacgaacatgt
acggcaaccccgaggcgacggtgaccacggtgatcgtcccagcggagctt
gccccgggtcagacctgccccttgctgtcgtaccagtgtgcgatcgatgc
catgtcgtcgcgctgttttccgtcatatgccctgcgacgacgggccaagg
ccctggggtcactgacccaaatggagctgttgatgatcagcgccgcactt
gccgaaggatgggcggtatcagtacccgaccatgaagggccgaaagggct
gtgggggtcgccgtatgaacccggttaccgagtcctcgacggaatccggg
ctgccttgaattccgagcgtgtcgggttgtccccggcaacgccgatcggg
ctgtggggctactccggcggcgggctggccagcgcgtgggccgccgaagc
atgcggcgagtacgcaccggacctagacatcgtcggcgccgtgctgggat
cacccgtcggtgaccttggtcacacgttccgccggctcaatggcactctt
cttgccggtctgcccgcgttggtggtggccgcgctgcaacacagctaccc
cggcctggcccgggtgatcaaggagcacgccaacgacgaaggacgtcagc
tgctggagcaactgacggagatgacaacggtagacgcagtgatccggatg
gccggcagggacatgggtgacttcctcgacgaaccccttgaggacattct
gtcgacgccggaaatttcccatgtcttcggcgacaccaagctgggtagcg
cggtgcccaccccgccggtattgatcgtgcaggccgtgcatgactacctc
atcgacgtctctgacatcgacgcgctcgctgacagctatacagccggcgg
cgccaacgtcacctaccaccgcgacctgttcagcgaacatgtgtccctgc
acccgctgtcggccccaatgacgcttcgctggctcaccgaccggttcgcc
ggcaagccactgaccgaccaccgcgtccggaccacgtggccgaccatctt
caacccgatgacctacgccggcatggcgagactggccgtgatcgcggcca
aggtgatcaccggcaggaagttgagccgccgtccgctc Rv1733c 54
atgatcgccacaacccgcgatcgtgaaggagccaccatgatcacgtttag
gctgcgcttgccgtgccggacgatactgcgggtgttcagccgcaatccgc
tggtgcgtgggacggatcgactcgaggcggtcgtcatgctgctggccgtc
acggtctcgctgctgactatcccgttcgccgccgcggccggcaccgcagt
ccaggattcccgcagccacgtctatgcccaccaggcccagacccgccatc
ccgcaaccgcgaccgtgatcgatcacgagggggtgatcgacagcaacacg
accgccacgtcagcgccgccgcgcacgaagatcaccgtgcctgcccgatg
ggtcgtgaacggaatagaacgcagcggtgaggtcaacgcgaagccgggaa
ccaaatccggtgaccgcgtcggcatttgggtcgacagtgccggtcagctg
gtcgatgaaccagctccgccggcccgtgccattgcggatgcggccctggc
cgccttgggactctggttgagcgtcgccgcggttgcgggcgccctgctgg
cgctcactcgggcgattctgatccgcgttcgcaacgccagttggcaacac
gacatcgacagcctgttctgcacgcagcgg Rv1734c 55
atgaccaacgtcggtgaccagggggttgacgcggtcttcggggtgatcta
cccacctcaggtcgcgctggtcagtttcggcaagccggcacaacgagttt
gcgccgtcgacggcgcgatccacgtcatgacgaccgtgctggctacgctg
cccgctgaccacggctgcagcgatgaccatcgcggcgcgctgttcttcct
gtcgatcaacgagctgacgcggtgcgccgcagtaacagga Rv1736c 56
gtgacggtgacaccacggaccggcagccgcatcgaggagctgcttgcacg
cagcggccggttcttcatcccgggtgagatctcggcggatctgcgtaccg
tgacccgccgcggcggccgcgacggcgacgtgttctatcgagaccggtgg
agccacgacaaggtggtccgctccacacacggggtgaattgcaccgggtc
gtgttcttggaagatctacgtcaaagacgacatcatcacctgggagacgc
aggagaccgactatccgtcggtgggcccggaccggcccgagtatgagccc
cgcggctgcccgcgcggcgcggcgttttcctggtacacgtattcgccgac
gcgggtgcgccatccgtacgcccgcggcgtgcttgtcgagatgtatcggg
aggcgaaggcacgtttgggtgatccggtggcggcctgggccgacatccag
gccgacccgcggcggcgccgccgctaccagcgcgcccgcggcaagggcgg
gctggtccgggtcagctgggccgaggccaccgagatgatcgccgccgccc
acgtgcacaccatctccacatacggcccggaccgggttgccggcttctcc
cccatcccggcgatgtccatggtgagccacgccgcggggtcgcggttcgt
ggagctaatcggcggggtgatgacgtcgttctacgactggtacgccgacc
tgccggtggcctccccgcaggtgttcggcgaccagaccgacgtgccggag
tccggagattggtgggacgtggtgtggcaatgcgcctcggtgctgctgac
ctacccgaactcacggcaactcggcaccgcagaggaattgctggcccaca
tcgacggtccggccgcggatctgttggggcgcacggtctctgagctgcgc
cgtgccgatccgctgaccgcggcgacccgctacgtcgacaccttcgacct
gcgaggccgcgccaccctgtacctgacctactggaccgccggcgacaccc
gcaaccgcggccgggagatgctggccttcgcccagacctaccgcagcacc
gacgtcgcaccaccgcgcggcgagaccccggacttcctgccggtggtgct
cgaattcgccgcgaccgtcgaccccgaggcggggcgacggttgctgagcg
ggtaccgggtgcccatcgccgcgctgtgcaatgccctgaccgaggccgca
ttgccatacgcacacacggtggccgcggtatgccggacgggtgacatgat
gggcgaactcttctggaccgtcgtgccgtatgtgacgatgacgatcgtcg
cggtcggctcctggtggcgctaccgctatgacaaattcggctggaccacc
cgctcgtcccagctgtacgagtcgcggctgctgcggatcgccagcccgat
gtttcatttcggcatcctggtggtcatcgtcggccacggtatcgggctcg
tgatcccgcagtcgtggactcaggccgccggtttgagcgagggcgcatat
cacgtgcaggccgtcgtgctggggtcgatcgccggcatcaccaccttggc
cggcgttaccctgctgatctaccggcggcgcacccgcgggccggtgttca
tggctaccaccgtcaacgacaaggtgatgtacctcgtgctggtggcggcg
atcgtcgcgggactgggtgcgacggcgttgggctccggcgttgtcggcga
ggcgtacaactaccgcgagacggtgtcggtgtggttccgctcggtgtggg
tactgcaaccgcgcggggacctgatggccgaggctccgctgtattaccag
atccatgtgctgatcgggttggcgttgttcgcgttgtggccgttcacccg
gctggtacacgcgttcagcgccccgatcggctatctgttccgcccgtaca
tcatctaccgcagccgcgaggagctggtgctaacgcggccgcggcggcgc gggtgg Rv1737c
57 atgagagggcaagcggccaatctcgtgctggccacctggatctcggtggt
caacttctgggcgtggaacctgatcggcccgctgtcgaccagctacgcgc
gtgacatgtcactgtccagcgccgaggcgtcgctgctcgtcgccaccccg
atcctggtgggtgcccttggccgcatcgtcaccgggccgctcaccgaccg
cttcggcgggcgcgccatgctcatcgcggtgacgctggcgtcgatcctcc
cggtgctcgcggtcggggtcgcggcaaccatgggctcctacgcgttgctg
gtgtttttcgggctcttcctgggcgttgccggcacgatcttcgccgtcgg
catcccgttcgccaacaactggtaccagccggcgcggcgcggtttctcca
ccggcgtgttcggtatgggcatggtcggcaccgcgctctcggcgttcttc
accccgcggtttgtacggtggttcggcctgttcaccacccacgccatcgt
cgcggccgcgctcgcgtcgaccgccgtggtggccatggtcgtgcttcgtg
atgcaccctactttcggcccaacgccgacccggtgctgcccaggctcaag
gccgcggcacggttgccggtgacctgggagatgtcgtttctgtacgcgat
cgtgttcggcgggttcgtggcgttcagcaactacctgcccacctacatca
ccacgatctacgggttctccacggtcgacgcgggcgctcgcaccgccggg
ttcgccctggcggcggtgctggcccggccggtgggcgggtggctctccga
ccggatcgcaccgaggcacgtggtgctggcctcgctcgccgggaccgcgc
tgctggcgttcgccgcggcgttgcagccgccgccggaggtgtggtcggcg
gccaccttcatcaccctggcggtctgcctcggcgtgggcaccggcggcgt
gttcgcgtgggtggcccgccgcgccccggccgcatcggtcggctcggtca
ccggaatcgtcgccgcggcaggcggattgggcggttacttcccgccgctg
gtgatgggcgcgacctacgacccggtcgacaacgactacacggtcgggtt
gctgctgctggtggcgaccgcgctggtcgcgtgtacctacaccgcgctgc
acgcgcgggagccggtgagtgaggaggcgtccagg Rv1738 58
atgtgcggcgaccagtcggatcacgtgctgcagcactggaccgtcgacat
atcgatcgacgaacacgaaggattgactcgggcgaaggcacggctgcgtt
ggcgggaaaaggaattggtgggtgttggcctggcaaggctcaatccggcc
gaccgcaacgtccccgagatcggcgatgaactctcggtcgcccgagcctt
gtccgacttggggaagcgaatgttgaaggtgtcgacccacgacatcgaag
ctgttacccatcagccggcgcgattgttgtat Rv1739c 59
atgattcccacgatgacatcggccggctgggcaccaggggtggtgcagtt
ccgcgaataccaacggcgttggctgcgcggcgatgtcctcgccggcctga
ccgtggccgcctatctgatcccgcaagcgatggcgtatgcgaccgtggcg
ggcctaccgccggcagccgggctgtgggcgtcgatcgcgccgcttgccat
ttacgcactgctcggatcgtcccggcagctttcaatcggcccggaatccg
ccaccgccttgatgacggcggccgtgctcgctccgatggccgccggggat
cttcgacgctatgccgttctggcggcaaccctcggattgctagtcggcct
tatctgcctactcgctggcacggcgcgactaggtttcctcgccagcctgc
gatcgcggccggtgctcgtcggatacatggccggcatcgcgcttgtcatg
atctccagccaactcggcactatcaccggcacctcggtcgaaggcaacga
attcttcagcgaagtacactctttcgcgactagcgtcacgcgagttcact
ggccgacttttgtgttagccatgtctgtcctagcgctgctaactatgctc
acgcggtgggcgccgcgcgcccccggaccgatcatcgcggttcttgcggc
cacgatgctagtggccgttatgtccttggatgccaaaggtattgcgattg
tgggtcggataccttccggtctgccgacgccgggtgtgccgcccgtttcg
gtggaagacttgcgggcactgatcattccggctgccgggatcgcgattgt
taccttcaccgacggtgtgttgaccgcacgcgccttcgccgctcgtcgag
gtcaggaagtcaatgccaacgccgagctgcgcgcggtcggggcctgcaac
atcgccgccgggctgacacacggttttccggtgagttccagcagcagccg
taccgccctcgccgacgtcgtcggtggccgcacccagctgtactcgctga
tcgcgttggggcttgttgtcatcgtgatggttttcgcgagtgggctgctg
gccatgtttccgatcgccgctctgggcgctttggtggtatatgccgcgct
acgcttgatcgacttgtcagaattccggcgactggcgcggtttcggcgca
gcgaactcatgctggcactagccaccacagcagccgtgttaggcctagga
gtgttctatggagtcctcgccgcggttgccctgtccatcctcgaactgct
tcgtcgggtcgcacatccgcatgacagcgttctcgggttcgtgccgggca
ttgccggcatgcacgacatcgatgactatccgcaggccaagcgcgtgccc
gggctggtggtgtatcgctatgacgcgccgttgtgcttcgccaatgccga
agacttccgcaggcgagcactgaccgtggtcgatcaggatccggggcaag
tcgagtggttcgtactcaacgccgaatccaatgtggaggtcgacctgact
gcgctggatgcgctcgaccaactccgcaccgagctgctgcgtcggggaat
agtgttcgccatggcccgggtcaaacaagacttgcgtgaatcactcaggg
ccgccagtcttctcgataagattggcgaagaccatatctttatgacattg
cctaccgcagtgcaggcgttccgtcggcgc Rv1813c 60
atgatcacaaacctccgacgccgaaccgcgatggcagccgccggcctagg
ggctgctctcgggctgggcatcctgctggttccgacggtggacgcccatc
tcgccaacggttcgatgtcggaagtcatgatgtcggaaattgccgggttg
cctatccctccgattatccattacggggcgattgcctatgcccccagcgg
cgcgtcgggcaaagcgtggcaccagcgcacaccggcgcgagcagagcaag
tcgcactagaaaagtgcggtgacaagacttgcaaagtggttagtcgcttc
accaggtgcggcgcggtcgcctacaacggctcgaaataccaaggcggaac
cggactcacgcgccgcgcggcagaagacgacgccgtgaaccgactcgaag
gcgggcggatcgtcaactgggcgtgcaac Rv1997 61
ttgtcggcgtcagtgtctgccacgacggctcatcatggcttgccagcaca
tgaagtggtgctgctgctggagagcgatccatatcacgggctgtccgacg
gcgaggccgcccaacgactagaacgcttcgggcccaacaccttggcggtg
gtaacgcgcgctagcttgctggcccgcatcctgcggcagtttcatcaccc
gctgatctacgttctgctcgttgccgggacgatcaccgccggtcttaagg
aattcgttgacgccgcagtgatcttcggtgtggtggtgatcaatgcgatc
gtgggtttcattcaagaatccaaggcagaggccgcactgcagggcctgcg
ctccatggtgcacacccacgccaaggtggtgcgcgagggtcacgagcaca
caatgccatccgaagagctggttcccggtgaccttgtgctgttagcggcc
ggtgacaaggttcccgccgatttgcggctggtgcgacagaccggattgag
cgtgaacgagtcagcacttaccggcgagtcgacgccggttcacaaggacg
aggtggcgttgccggagggcacaccggtcgctgatcgtcgcaatatcgcg
tattccggcacattggtaaccgcgggccatggcgccgggatcgtcgtcgc
gaccggcgccgaaaccgaactcggtgagattcatcggctcgttggggccg
ccgaggttgtcgccacaccgctgaccgcgaagctggcgtggttcagcaag
tttctgaccatcgccatcctgggtctggcagcgctcacgttcggcgtggg
tttgctgcgccggcaagatgccgtcgaaacgttcaccgctgcgatcgcgc
tggcggtcggggcaattcccgaaggtctgcccaccgccgtgaccatcacc
ttggccatcggcatggcccggatggccaagcgccgcgcggtcattcgacg
tctacccgcggtggaaacgctgggcagcaccacggtcatctgcgccgaca
agaccggaacgctgaccgagaatcagatgacggtccagtcgatctggaca
ccccacggtgagatccgggcgaccggaacgggctatgcacccgacgtcct
cctgtgcgacaccgacgacgcgccggttccggtgaatgccaatgcggccc
ttcgctggtcgctgctggccggtgcctgcagcaacgacgccgcactggtt
cgcgacggcacacgctggcagatcgtcggcgatcccaccgagggcgcgat
gctcgtcgtggccgccaaggccggcttcaacccggagcggctggcgacaa
ctctgccgcaagtggcagccataccgttcagttccgagcggcaatacatg
gccaccctgcatcgcgacgggacggatcatgtggtgctggccaagggtgc
tgtggagcgcatgctcgacctgtgcggcaccgagatgggcgccgacggcg
cattgcggccgctggaccgcgccaccgtgttgcgtgccaccgaaatgttg
acttcccgggggttgcgggtgctggcaaccgggatgggtgccggcgccgg
cactcccgacgacttcgacgaaaacgtgataccaggttcgctggcgctga
ccggcctgcaagcgatgagcgatccaccacgagcggccgcggcatcggcg
gtggcggcctgccacagtgccggcattgcggtaaaaatgattaccggtga
ccacgcgggcaccgccacggcgatcgcaaccgaggtggggttgctcgaca
acactgaaccggcggcaggctcggtcctgacgggtgccgagctggccgcg
ctgagcgcagaccagtacccggaggccgtggatacagccagcgtgtttgc
cagggtctctcccgagcagaagctgcggttggtgcaagcattgcaggcca
gggggcacgtcgtcgcgatgaccggcgacggcgtcaacgacgccccggcc
ttgcgtcaggccaacattggcgtcgcgatgggccgcggtggcaccgaggt
cgccaaggatgccgccgacatggtgttgaccgacgacgacttcgccacca
tcgaagccgcggtcgaggaaggccgcggcgtattcgacaatctgaccaag
ttcatcacctggacgctgcccaccaacctcggtgagggcctagtgatctt
ggccgccatcgctgttggcgtcgccttgccgattctgcccacccaaattc
tgtggatcaacatgaccacagcgatcgcgctcggactcatgctcgcgttc
gagcccaaggaggccggaatcatgacccggccaccgcgcgaccccgacca
accgctgctgaccggctggcttgtcaggcggactcttctggtttccacct
tgctcgtcgccagcgcgtggtggctgtttgcatgggagctcgacaatggc
gcgggcctgcatgaggcgcgcacggcggcgctgaacctgttcgtcgtcgt
cgaggcgttctatctgttcagctgccggtcgctgacccgatcggcctggc
ggctcggcatgttcgccaaccgctggatcatcctcggcgtcagtgcgcag
gccatcgcgcaattcgcgatcacatatctacccgcgatgaatatggtgtt
cgacaccgcgccaatcgatatcggggtgtgggtgcgcatattcgctgtcg
cgaccgcaatcacgattgtggtggccaccgacacgctgctgccgagaata cgggcgcaaccgcca
Rv1998c 62 atgagtttccacgatcttcatcaccaaggtgttccgttcgtgttgcccaa
cgcctgggatgtgccgtcggccctggcctacctcgcggagggcttcacgg
ctatcggcacaaccagtttcggggtctcgtccagcggcgggcacccggac
gggcaccgcgccactcgcggcgccaacatcgcactggcggccgccctggc
accgctgcaatgctacgtcagcgtcgacatcgaggacggatacagcgacg
aacccgacgccattgctgactacgtcgcacaactgtcgacagccggaatc
aatatcgaggacagtagcgccgaaaagctcatcgaccccgccctggcagc
cgctaaaatcgttgcgatcaaacaacgtaaccccgaggtgttcgtcaacg
cccgcgtcgacacctattggttgcgccagcacgccgataccaccagcacg
atccagcgcgcacttcgctacgtcgatgccggcgccgacggcgtctttgt
cccactggccaacgatcccgacgaacttgctgagctcactcgcaacattc
cgtgcccggttaacacgttgcccgtgcccggcttgacgatcgccgacctt
ggtgagctcggggtggcccgggtgtcaaccggttcagtgccctacagcgc
ggggttgtatgcagcggcccacgcggctcgggccgtgagcgacggagagc
agctgccacggtccgtaccgtacgccgaactgcaggcacgcttggttgac
tacgagaaccgcacgagtacaacg Rv2003c 63
gtggtcaagcgctctcgggcaacccgactttcgccgagcatctggtccgg
atgggaatcacctcagtgtcggtccattcgggcgcgattgctgctacccc
ggggtcggtcgcggccgccgaacgccgattgttgctggaatcagctcgcg
gtgacgcctgacacccggatgccggcatcgtcggccgccgggcgcgacgc
ggcggcctacgacgcctggtatgactcacccaccgggcggccgatcctgg
cgaccgaggtcgccgcgttgcggccgctcatcgaggtctttgcccagcca
cgcttggaaatcggtgtcggtacaggacgtttcgccgacctgctcggcgt
gcggttcggactcgatccatcccgtgatgcgctgatgttcgcacgccggc
gcggcgtcctggtcgccaatgccgtcggcgaggcggtccctttcgtcagc
cggcacttcggggcggtcctcatggcattcacgctctgtttcgtcaccga
cccggccgccatattccgggaaacgcggcgtctgctcgccgacggcggcg
gccttgttatcgggttcttgcctcgcgggacaccgtgggccgacctgtac
gctctgcgcgcggcccgcggacagccaggctaccgcgacgcccgcttcta
caccgcggccgaactcgaacaactgctcgcagactcgggattccgggtca
tcgcccgccgctgcacgctgcaccaaccgccgggactcgcccggtacgac
atcgaagccgcccatgacggtatccaagccggcgccggcttcgttgctat
ctcggcggtcgaccaagcgcacgagcctaaggatgatcacccactcgagt cggaa Rv2005c 64
atgtctaaaccccgcaagcagcacggagttgtcgtcggggtagatggttc
gctcgaatcggatgccgccgcctgttggggtgccaccgatgcggcgatga
ggaacattccgctgaccgtggtccacgtggtgaacgccgatgtagcgacg
tggccgccgatgccgtatccggagacctggggggtttggcaggaggacga
gggtcgccagatcgtcgccaacgccgtcaagctcgccaaagaggcggttg
gagcggatcgaaagctcagcgtaaagagcgagctcgtattttccacgccg
gtacctaccatggttgaaatctccaacgaggcagagatggtggtgttggg
cagctcgggccggggagcgctggcccgaggcttgctcggttcggtcagct
cgagcctggtgcgacgcgccgggtgcccggtcgcggtcatccacagcgat
gatgcggtgatccctgatccgcagcacgctcccgtgctggtgggaatcga
cggttcgccggtttcggagcttgcgacggcggtggcatttgacgaggcgt
cgcgccgcggcgtcgaactgatcgccgtgcacgcgtggagtgacgtcgaa
gtggtggaacttccgggtttggacttctcggctgtacagcaggaagcgga
gcttagtctcgccgaacgcttggcaggttggcaagaacgctatcccgatg
tgccggtgagccgggttgtcgtttgcgatcgcccggcgcggaagctggtg
caaaagtcggcgtccgcccagcttgtcgtcgttggcagtcatggccgagg
tggcttgaccggcatgcttctggggtcggtcagtaacgcggtcttacacg
ccgcgcgggtgccagtgatcgtggcacggcagtcg Rv2007c 65
gtgacctatgtgatcggtagtgagtgcgtggatgtgatggacaagtcctg
tgtgcaggagtgtccggtcgactgtatctatgagggcgcccgaatgctct
acatcaaccccgacgagtgcgtggattgtggtgcgtgcaaaccggcctgc
cgcgtcgaggcgatctactgggaaggcgatctacccgacgatcaacacca
gcatctgggggacaacgccgcctttttccaccaagtcctgccgggccgag
tggctccgctgggttcgccgggtggtgccgcagcggtgggcccgatcgga
gtcgacacgcctctggtcgcggctatcccggtggagtgccct Rv2028c 66
atgaaccaatcacacaaacccccatcgatcgtcgtcggtattgatggctc
gaagccggccgtgcaagccgcactgtgggcggtcgacgaggcagccagcc
gtgacatcccgctgcgtctgctgtacgcgatcgaacccgacgatcccggg
tacgccgcacacggcgcggcggctcgcaaactcgccgccgccgagaacgc
ggtgcgctacgcgttcacagcggtcgaggcggcggaccggccggtcaagg
tcgaggtggagatcacccaggagcggccggtcacctcgttgatccgcgct
tcggcggctgctgccctggtgtgcgttggcgctatcggcgtgcaccactt
ccgaccggagcgggtgggatctaccgcagcggccctggcgttatcggcgc
agtgcccagtggcgatcgtgcgaccccaccgggtccccatcggacgcgac
gccgcatggatcgtcgtcgaggcggacgggtcgtccgatatcggtgtttt
gctgggggcggtgatggccgaagcacggctgcgcgactcgccggttcggg
tggtcacctgccggcaatccggagtgggcgataccggggacgacgtccgt
gccagcctggaccgctggcttgcccgttggcaaccacggtatcccgatgt
gcgggtgcaatcggcggcagtgcacggcgagctgctggattatctggctg
ggctgggtcgatcggtacacatggtggtgctcagcgcgagcgaccaggag
catgtggagcaacttgtgggagcgccgggcaacgccgtgttgcaggaggc
cggctgcaccctgctggtcgtcggtcagcagtatctg Rv2029c 67
atgacggagccagcggcgtgggacgaaggcaagccgcgaatcatcacttt
gaccatgaaccccgccttggacatcacgacgagcgtcgacgtggtgcgcc
cgaccgagaaaatgcgttgtggcgcacctcgctacgatcccggcggcggc
ggtatcaatgtcgcccgcattgtgcatgtcctcggcggttgctcgacagc
actgttcccggccggcgggtcgaccgggagcctgctgatggcgctgctcg
gtgatgcgggagtgccatttcgcgtcattccgatcgcggcctcgacgcgg
gagagcttcacggtcaacgagtccaggaccgccaagcagtatcgtttcgt
gcttccggggccgtcgctgaccgtcgcggagcaggagcaatgcctcgacg
aactgcgcggtgcggcggcttcggccgcctttgtggtggccagtggcagc
ctgccgccaggtgtggctgccgactactatcagcgggttgccgacatctg
ccgccgatcgagcactccgctgatcctggatacatctggtggcgggttgc
agcacatttcgtccggggtgtttcttctcaaggcgagcgtgcgggaactg
cgcgagtgcgtcggatccgaactgctgaccgagcccgaacaactggccgc
cgcacacgaactcattgaccgtgggcgcgccgaggtcgtggtggtctcgc
ttggatctcagggcgcgctattggccacacgacatgcgagccatcgattt
tcgtcgattccgatgaccgcggttagcggtgtcggcgccggcgacgcgat
ggtggccgcgattaccgtgggcctcagccgtggctggtcgctcatcaagt
ccgttcgcttgggaaacgcggcaggtgcagccatgctgctgacgccaggc
accgcggcctgcaatcgcgacgatgtggagaggttcttcgagctggcggc
cgaacccaccgaagtcgggcaggatcaatacgtttggcacccgatcgtta
acccggaagcctcggca Rv2030c 68
gtgctgatgaccgcagcggctgatgtcacccggcgctcgccgcggcgcgt
gttccgtgaccgccgcgaggccggccgggtgctggcggaattactcgccg
cctatcgggaccagccggacgtgattgtgctcggcttggcccggggtggc
ctcccggtcgcatgggaggttgccgcggcactgcatgccccgctagacgc
cttcgtcgtgcgcaaacttggtgccccggggcatgacgagttcgccgttg
gtgcactggccagcggcggccgcgtcgtggtcaatgacgacgtcgtgcgg
ggcctgcggatcacaccgcagcaactgcgcgacatcgccgaacgtgaggg
tcgggaactgcttcggcgcgagtccgcctaccgcggcgagcgcccgccca
ccgatatcaccggcaagacggtcattgtcgtcgatgacggtttggccacc
ggcgcaagcatgttcgcggcggtacaggcattgcgcgatgcgcaaccagc
gcagatcgtgattgccgtgccggcggcgccggagtccacgtgccgggagt
tcgccggcctcgtcgacgacgttgtgtgcgcgaccatgccgaccccgttc
ctggccgtcggtgagtcgttttgggacttccggcaggtcaccgacgagga
ggtccgccggctcctggccaccccgaccgctgggccgtcgctgcgccggc
ccgcggcgtcaacggcggccgatgttctgcgcagagtcgcgatcgacgcc
cccgggggtgttccgacgcacgaggtgttggcggagctggtcggcgatgc
acgaatcgtgttgatcggcgaaagctcgcacggcacacacgagttctacc
aggcccgggccgccatgacacagtggctgatcgaggagaagggctttggt
gcggtagccgccgaggcggactggcccgacgcctaccgggtcaatcggta
cgttcgcggcctcggcgaggacaccaacgctgacgaggcgcttagcggat
tcgagcggtttcccgcctggatgtggcgcaacaccgtggtccgagatttt
gtggaatggctgcgcacacgcaaccagcgctacgagtcgggcgcgctgcg
gcaagccggcttctacggtctggatctttacagcctgcatcggtcgatcc
aagaggtgatcagctatctcgacaaggtcgacccgcgtgcggcggcacgg
gcgcgggcccggtatgcgtgcttcgaccatgcctgcgccgatgacggtca
ggcgtacggattcgcggccgcattcggcgccggtccgtcgtgcgaacgtg
aagccgtcgagcaactggtcgacgttcagcgcaatgccctggcgtatgcg
cgccaagacgggctgcttgccgaggacgaactgttctacgcccagcaaaa
cgcgcagacggtgcgcgacgcagaggtgtattaccgggccatgttcagtg
gacgcgttacctcgtggaacctgcgcgaccagcacatggcgcagaccctt
ggcagtttgctgacgcatttggaccgacacctcgatgcgccgccggcgcg
aatagtggtgtgggctcataactcccacgtgggtgacgcacgcgctaccg
aggtgtgggccgacgggcagctcaccctcggccagatagtccgtgagcga
tacggtgacgagtcgcgcagcatcggattcagcacgtacacgggcaccgt
caccgcggccagcgaatggggtggtatcgcccaacgcaaagcggttcggc
cggcactgcacggcagtgtcgaggagctcttccaccagactgcagacagt
ttcctggtgtcagcgcggctaagccgcgacgccgaagccccgctggacgt
tgtccggttgggacgtgccatcggcgtcgtttatctaccggcaacggaac
ggcaaagtcactacttgcacgtgcggcccgccgaccagttcgacgccatg
atccacatcgatcagacccgtgccctggaacctctcgaggtgacgagccg
gtggatcgccggcgagaacccggaaacctacccgaccggtctg Rv2031c 69
Atggccaccacccttcccgttcagcgccacccgcggtccctcttccccga
gttttctgagctgttcgcggccttcccgtcattcgccggactccggccca
ccttcgacacccggttgatgcggctggaagacgagatgaaagaggggcgc
tacgaggtacgcgcggagcttcccggggtcgaccccgacaaggacgtcga
cattatggtccgcgatggtcagctgaccatcaaggccgagcgcaccgagc
agaaggacttcgacggtcgctcggaattcgcgtacggttccttcgttcgc
acggtgtcgctgccggtaggtgctgacgaggacgacattaaggccaccta
cgacaagggcattcttactgtgtcggtggcggtttcggaagggaagccaa
ccgaaaagcacattcagatccggtccaccaac Rv2032 70
atgccggacaccatggtgaccaccgatgtcatcaagagcgcggtgcagtt
ggcctgccgcgcaccgtcgctccacaacagccagccctggcgctggatag
ccgaggaccacacggttgcgctgttcctcgacaaggatcgggtgctttac
gcgaccgaccactccggccgggaagcgctgctggggtgcggcgccgtact
cgaccactttcgggtggcgatggcggccgcgggtaccaccgccaatgtgg
aacggtttcccaaccccaacgatcctttgcatctggcgtcaattgacttc
agcccggccgatttcgtcaccgagggccaccgtctaagggcggatgcgat
cctactgcgccgtaccgaccggctgcctttcgccgagccgccggattggg
acttggtggagtcgcagttgcgcacgaccgtcaccgccgacacggtgcgc
atcgacgtcatcgccgacgatatgcgtcccgaactggcggcggcgtccaa
actcaccgaatcgctgcggctctacgattcgtcgtatcatgccgaactct
tttggtggacaggggcttttgagacttctgagggcataccgcacagttca
ttggtatcggcggccgaaagtgaccgggtcaccttcggacgcgacttccc
ggtcgtcgccaacaccgataggcgcccggagtttggccacgaccgctcta
aggtcctggtgctctccacctacgacaacgaacgcgccagcctactgcgc
tgcggcgagatgctttccgccgtattgcttgacgccaccatggctgggct
tgccacctgcacgctgacccacatcaccgaactgcacgccagccgagacc
tggtcgcagcgctgattgggcagcccgcaactccgcaagccttggttcgc
gtcggtctggccccggagatggaagagccgccaccggcaacgcctcggcg
accaatcgatgaagtgtttcacgttcgggctaaggatcaccgg Rv2428 71
atgccactgctaaccattggcgatcaattccccgcctaccagctcaccgc
tctcatcggcggtgacctgtccaaggtcgacgccaagcagcccggcgact
acttcaccactatcaccagtgacgaacacccaggcaagtggcgggtggtg
ttcttttggccgaaagacttcacgttcgtgtgccctaccgagatcgcggc
gttcagcaagctcaatgacgagttcgaggaccgcgacgcccagatcctgg
gggtttcgattgacagcgaattcgcgcatttccagtggcgtgcacagcac
aacgacctcaaaacgttacccttcccgatgctctccgacatcaagcgcga
actcagccaagccgcaggtgtcctcaacgccgacggtgtggccgaccgcg
tgacctttatcgtcgaccccaacaacgagatccagttcgtctcggccacc
gccggttcggtgggacgcaacgtcgatgaggtactgcgagtgctcgacgc
cctccagtccgacgagctgtgcgcatgcaactggcgcaagggcgacccga
cgctagacgctggcgaactcctcaaggcttcggcc Rv2624c 72
atgtctgggagaggagagccgacgatgaaaacaatcattgttggtatcga
tggttcgcacgcggcgattacggccgcattgtggggggttgacgaggcca
tcagccgagcggtgccgctgcgactggtctcagtgatcaagccgacacat
ccgtccccggacgactacgaccgcgaccttgcgcatgctgaaagatcgct
tcgggaagcgcagtccgctgttgaggccgcgggcaagctcgtcaagatcg
aaaccgacatcccccgcgggccagccggcccggtgcttgtggaggcatcg
cgcgacgccgagatgatctgcgtcggctccgtgggaatcgggcgctacgc
cagctcgatcttgggttcgacggcaaccgagctggccgaaaaggcgcatt
gcccggtcgccgtcatgcgctcaaaagtggaccagccagcgtctgacatc
aactggatcgtggtgcgcatgaccgacgcaccggataacgaggccgtgct
ggaatacgctgcccgggaagcgaagttgcggcaagcgcccatactggcac
tcggcgggcgaccggaggagctccgggagattccggacggcgaattcgaa
cgtcgcgtgcaggattggcaccaccgtcatcccgatgtgcgcgtctaccc
gatcaccactcacacgggtattgcccggttcctggccgaccacgacgagc
gcgtacagctggcagtgatcggcggtggtgaggccggtcagctagcgcgg
ctggtcgggccatccggacatccggtgttccgtcacgccgagtgttcggt gcttgtcgttcgccgc
Rv2625c 73 atgcgtgatgcgatcccgcttgggcggatcgccgggtttgtggtgaacgt
ccactggagcgtgttggtgatcctgtggttgttcacctggagtctggcga
ccatgttgccgggtaccgtcggaggctacccggccgtggtctattggctt
ctcggcgcaggtggcgcggtcatgttgctggcgtcgctgttggctcatga
gctcgcgcacgccgtcgtcgctcgtcgcgccggggtatccgttgagagcg
tgacgttgtggctgttcggcggggtgaccgcgcttggcggcgaggcaaag
acgcccaaagccgctttccggatcgcgttcgcgggtccggctaccagcct
ggcgctgtcggcgacattcggtgcgttggccatcacgctcgccggcgtgc
ggaccccggccatcgtgatcagcgttgcttggtggttggctactgtcaac
ctgctgctggggctgttcaatctgctgcctggcgcgccgttggacggtgg
gcggttggtccgggcctatctgtggcgccgccacggcgatagtgtgcgcg
ccgggatcggtgcggcgcgggccggacgggtggttgcgctggtcttgatc
gcgttgggattggccgagtttgtggctggtggcctcgtcggtggggtctg
gttagccttcattggctggtttatcttcgctgccgctcgcgaggaggaga
cccggatttcgacccagcagctgtttgccggggtgcgtgtggccgatgcg
atgaccgcccaaccgcatacggctcccggatggatcaatgtcgaggattt
catccagcgttacgtgcttggtgaacggcactcggcatatccggttgccg
atcgggacggatcgatcacgggcctggtggcattgcggcagctgcgcgat
gttgcgcctagccggcgcagcactaccagcgtaggtgacattgcgctgcc
gctgcacagcgtgccgaccgcccgaccacaagagccgctgaccgcgctcc
tagagcggatggcaccgctcggcccgcgcagccgtgcgctggtcaccgaa
gggagcgcggtggtcggcatcgtcactcccagcgatgtcgcgcggctgat
tgacgtctaccggttggcccagccggaaccgacctttaccacgagtcccc
aagatgcggacaggttttccgatgcgggg Rv2627c 74
atggcaagttctgcgagcgacggcacccacgaacgctcggcttttcgcct
gagtccaccggtcttgagcggcgccatgggaccgttcatgcacaccggtc
tgtacgtcgctcaatcgtggcgcgactatctgggtcaacagcccgataaa
ctgccgatcgcacggcccactattgccttagcggcgcaagcctttcgaga
cgaaatcgtcctgctgggcctcaaggcacgacgtccggtcagcaatcatc
gagtgttcgagcgcatcagccaagaagtggccgctggactggagttctat
gggaatcgcagatggctggagaagcctagcggattttttgcccagccccc
accgctcaccgaggtcgcggtccgaaaggtcaaggaccgcagacgctcct
tttatcgcatcttcttcgacagtgggtttacgccgcatccgggtgaaccg
ggcagccaacggtggctctcatacactgcgaacaatcgcgagtacgccct
gttactgcggcacccagagccgcgtccctggctggtttgtgtacacggca
ccgagatgggcagggccccgttggatctcgcggtgttccgcgcctggaag
ctgcatgacgaactcggcctgaacattgtcatgccggttcttccgatgca
tggtccccgcgggcaaggtctgccgaagggcgccgtttttcccggagaag
atgttctcgacgatgtgcatgggacggctcaagcggtgtgggatatccgg
cggctgttgtcctggatacgatcgcaggaggaggagtcgctgatcgggtt
gaacggtctctcgctgggcggctacatcgcgtcattggtcgccagcctcg
aagaaggtctcgcctgcgcgattctcggtgtcccagtggctgatctgatc
gagttgttgggccgccactgcggtcttcggcacaaagacccccgccgcca
caccgtcaagatggccgaaccgatcggccgaatgatctcgccgctctcac
ttacgccactggtgcccatgccgggccgctttatctacgcgggcattgcc
gaccgactcgtgcatccacgcgaacaggtgactcgcctctgggagcactg
gggcaaacccgaaatcgtgtggtatccaggcggtcacactggcttcttcc
agtcgcggccggtacgacggtttgtccaggctgcgctggagcagtcgggc
ctgttggacgcgccacggacacagcgcgaccgttccgcc Rv2628 75
Atgtccacgcaacgaccgaggcactccggtattcgggctgttggccccta
cgcatgggccggccgatgtggtcggataggcaggtggggggtgcaccagg
aggcgatgatgaatctagcgatatggcacccgcgcaaggtgcaatccgcc
accatctatcaggtgaccgatcgctcgcacgacgggcgcacagcacgggt
gcctggtgacgagatcactagcaccgtgtccggttggttgtcggagttgg
gcacccaaagcccgttggccgatgagcttgcgcgtgcggtgcggatcggc
gactggcccgctgcgtacgcaatcggtgagcacctgtccgttgagattgc cgttgcggtc
Rv2629 76 atgcgatcagaacgtctccggtggctggtagccgcagaaggtccgttcgc
ctcggtgtatttcgacgactcgcacgacactcttgatgccgtcgagcgcc
gggaagcgacgtggcgcgatgtccggaagcatctcgaaagccgcgacgcg
aagcaggagctcatcgacagcctcgaagaggcggtgcgggattctcgacc
ggccgtcggccagcgtggccgcgcgctgatcgcgaccggcgagcaagtac
tggtcaacgagcatctgatcggcccaccaccggctacggtgattcggctg
tcggattatccgtacgtcgtgccattgatagaccttgagatgcggcgacc
gacgtatgtatttgccgcggttgatcacaccggcgccgacgtcaagctgt
atcagggggccaccatcagttccacgaaaatcgatggggtcggctacccg
gtgcacaagccggtcaccgccggctggaacggctacggcgacttccagca
caccaccgaagaagccatccgaatgaactgccgcgcggtcgccgaccatc
tcacccgactggtagacgctgccgaccccgaggtggtgttcgtgtccggc
gaggtgcggtcacgcacagacctgctttccacattgccgcagcgggtggc
ggtccgggtgtcgcagctgcatgccggaccgcgcaaaagcgccttagacg
aggaagagatctgggacctgacatccgcggagttcacccggcggcggtac
gccgaaatcaccaatgtcgcacaacaatttgaggcggagatcggacgcgg
atcggggctggcggcccaagggttggcggaggtgtgtgcggctctgcgtg
acggcgacgtcgacacgctgatcgtcggagagctaggcgaggccaccgtg
gtcaccggtaaagcgcgtactacggtcgcgcgggatgccgacatgttgtc
cgaactcggcgaaccggtagatcgcgtggcaagggccgatgaggcgttgc
cattcgccgcgatcgcggtaggtgccgcattggtccgtgacgacaaccgg
atcgcgccactagatggggtgggcgcattgctgcgttatgccgccaccaa
ccgactcggcagccatagatcc Rv2630 77
Atgctgcaccgcgacgatcacatcaatccgccgcggccccgcgggttgga
tgttccttgcgcccgcctacgagcgacaaatcccctgcgcgccttggcgc
gttgcgttcaggcgggcaagccgggcaccagttcagggcatcggtccgtg
ccgcatacggcggacttgcgaatcgaagcctgggcaccgacccgtgacgg
ctgtatccggcaggcggtgctgggtaccgtcgagagcttcctcgacctgg
aatccgcgcacgcggtccatacccggctgcgccggctgaccgcggatcgc
gacgacgatctactggtcgcggtgctcgaggaggtcatttatttgctgga
caccgtcggtgaaacgcctgtcgatctcaggctgcgcgacgttgacgggg
gtgtcgacgtcacattcgcaacgaccgatgcgagtacgctagttcaggtg
ggtgccgtgccgaaggcggtgtcactcaacgaacttcggttctcgcaggg
tcgccacggctggcgatgtgcggtaacgctcgatgtg Rv2659c 78
Gtgacgcaaaccggcaagcgtcagagacgcaaattcggtcgcatccgaca
gttcaactccggccgctggcaagccagctacaccggccccgacggccgcg
tgtacatcgcccccaaaaccttcaacgccaagatcgacgccgaagcatgg
ctcaccgaccgccgccgcgaaatcgaccgacaactatggtccccggcatc
gggtcaggaagaccgccccggagccccattcggtgagtacgccgaaggat
ggctgaagcagcgtggaatcaaggaccgcacccgcgcccactatcgcaaa
ctgctggacaaccacatcctggccaccttcgctgacaccgacctacgcga
catcaccccggccgccgtgcgccgctggtacgccaccaccgccgtgggca
caccgaccatgcgggcacactcctacagcttgctgcgcgcaatcatgcag
accgccttggccgacgacctgatcgactccaacccctgccgcatctcagg
cgcgtccaccgcccgccgcgtccacaagatcaggcccgccaccctcgacg
agctggaaaccatcaccaaagccatgcccgacccctaccaggcgttcgtg
ctgatggcggcatggctggccatgcgctacggcgagctgaccgaattacg
ccgcaaagacatcgacctgcacggcgaggttgcgcgggtgcggcgggctg
tcgttcgggtgggcgaaggcttcaaggtgacgacaccgaaaagcgatgcg
ggagtgcgcgacataagtatcccgccacatctgatacccgccatcgaaga
ccaccttcacaaacacgtcaaccccggccgggagtccctgctgttcccat
cggtcaacgaccccaaccgtcacctagcaccctcggcgctgtaccgcatg
ttctacaaggcccgaaaagccgccggccgaccagacttacgggtgcacga
ccttcgacactccggcgccgtgttggctgcatccaccggcgccacactgg
ccgaactgatgcagcggctaggacacagcacagccggcgccgcactccgc
taccagcacgccgccaagggccgggaccgcgaaatcgccgcactgttaag
caaactggccgagaaccaggagatg Rv2780 79
Atgcgcgtcggtattccgaccgagaccaaaaacaacgaattccgggtggc
catcaccccggccggcgtcgcggaactaacccgtcgtggccatgaggtgc
tcatccaggcaggtgccggagagggctcggctatcaccgacgcggatttc
aaggcggcaggcgcgcaactggtcggcaccgccgaccaggtgtgggccga
cgctgatttattgctcaaggtcaaagaaccgatagcggcggaatacggcc
gcctgcgacacgggcagatcttgttcacgttcttgcatttggccgcgtca
cgtgcttgcaccgatgcgttgttggattccggcaccacgtcaattgccta
cgagaccgtccagaccgccgacggcgcactacccctgcttgccccgatga
gcgaagtcgccggtcgactcgccgcccaggttggcgcttaccacctgatg
cgaacccaagggggccgcggtgtgctgatgggcggggtgcccggcgtcga
accggccgacgtcgtggtgatcggcgccggcaccgccggctacaacgcag
cccgcatcgccaacggcatgggcgcgaccgttacggttctagacatcaac
atcgacaaacttcggcaactcgacgccgagttctgcggccggatccacac
tcgctactcatcggcctacgagctcgagggtgccgtcaaacgtgccgacc
tggtgattggggccgtcctggtgccaggcgccaaggcacccaaattagtc
tcgaattcacttgtcgcgcatatgaaaccaggtgcggtactggtggatat
agccatcgaccagggcggctgtttcgaaggctcacgaccgaccacctacg
accacccgacgttcgccgtgcacgacacgctgttttactgcgtggcgaac
atgcccgcctcggtgccgaagacgtcgacctacgcgctgaccaacgcgac
gatgccgtatgtgctcgagcttgccgaccatggctggcgggcggcgtgcc
ggtcgaatccggcactagccaaaggtctttcgacgcacgaaggggcgtta
ctgtccgaacgggtggccaccgacctgggggtgccgttcaccgagcccgc cagcgtgctggcc
Rv3126c 80 Atggtcatccggtttgatcaaatagggtcattggtcctctcaatgaaatc
ccttgcgtcactgtcgtttcagcggtgtctgcgcgagaattctagtttgg
tcgcggcgctggaccggctcgatgctgcggtcgatgagctgagcgctttg
tcgtttgatgcgttgaccactccggagcgggatcgcgcccgtcgcgaccg
ggaccatcatccttggtcccgctcccgctcgcagttgtcgccacgaatgg
cgcacggtgcagtgcaccaatgccagtggccgaaggcggtttgggctgtc attgacaatcca
Rv3127 81 Gtgctcaagaacgcagtcttgctggcatgccgggcgccgtcggtgcacaa
cagccagccctggcgttgggtggccgaaagcggctccgagcacactactg
tgcacctgttcgtcaaccgccaccgaacggtgccggccaccgaccattcc
ggccggcaagcgatcatcagttgcggtgccgtactcgatcaccttcgcat
cgccatgacggccgcgcactggcaggcgaatatcactcgctttccccagc
cgaaccaacctgaccagttggccaccgtcgaattcagtcccatcgatcac
gtcacggcgggacagcgaaaccgcgcccaggcgattctgcagcgccgaac
cgatcggcttccgtttgacagcccgatgtactggcacctgtttgagcccg
cgctgcgcgacgccgtcgacaaagacgttgcgatgcttgatgtggtatcc
gacgaccagcgaacacgactggtggtagcgtcacaactcagcgaagtcct
gcggcgggacgatccgtactatcacgccgaactcgaatggtggacttcac
cgttcgtgctggcccatggtgtgccgccggatacgctggcatcagacgcc
gaacgcttgcgggttgacctgggccgtgacttcccggtccggagctacca
gaatcgccgtgccgagctagctgatgaccgatcgaaagtccttgtgctgt
cgacccctagcgacacgcgagccgacgcactgaggtgtggcgaagtgctg
tcgaccatcctactcgagtgcaccatggccggcatggctacctgcacgtt
gacccatctgatcgaatccagtgacagtcgtgacatcgtgcggggcctga
cgaggcagcgaggcgagccgcaagccttgatccgggtagggatagccccg
ccgttggcagcagttcccgcccccacaccacggcggccgctggacagcgt
cttgcagattcgccagacgcccgagaaagggcgtaatgcctcagatagaa
atgcccgtgaaacgggttggttcagcccgcct Rv3128c 82
gtgtggtccgcctcgggtgggcagtgcgggaagtatcttgccgcctcgat
ggtgctgcagcttgatgggttggaacgtcacggtgtgttggagtttgggc
gtgaccgctatggccccgaggtgcgtgaggagctgttggcgatgagtgcg
gccagcatcgatcgttatctgaagaccgcgaaggccaaagaccagatatc
gggtgtgtcgacgacgaaaccctcaccactgctgcgtaattcgatcaagg
ttcgcagggccggcgatgaggtcgaggcggagccggggttcttcgagggc
gacaccgtcgcccattgcggtccgacgctcaaaggcgagttcgcccacac
cctgaacttgaccgacgtgcacatcggatgggtgttcacccgcaccgtcc
gcaacaacgcccgtacccacatcctcgccgggctcaaagcttctgtcacc
gagatcccgcatgggataacgggtttagatttcgacaacggcaccgtgtt
tctcaacaagccggtcatcagctgggccggcgacaacggtatctacttca
cccgctttcgcccgtacaagaaaaaccactaggccaccatcgagtccaag
aacaaccacctggtccgcaagtacgcgttctactaccgctatgacaccgc
cgaggaacgcgccgtgctcaaccggatgtggaagctggtcaacgaccgcc
tcaactacctcaccccgaccatcaaaccgatcgggtatgccagcagcgcc
gacggccgccgccgacgcctctacgatgccccacagacgccgctggaccg
gccactggccgcaagggtgctctccgcggcccagcaggccgacctgatca
cctaccgagacagcctcaaccccgcccagatcggccgcaaaatcgccgac
ctgcagaaccgactcctcatcttggccaaggagaaaaccgagcagctcta
cctcgctaacatccccaccgccctacccgacatccacaaaggcatcctga tcaaggcgggc
Rv3129 83 Gtggtgcaaggccgcaccgtgctgtttcgtaccgcggagggcgccaaatt
attttcagccgtcgcgaagtgcgcggtggctttcgaggcggacgaccaca
acgttgccgagggctggagcgtgatcgtcaaggttcgcgcccaggtgctg
acgaccgacgcgggggtccgcgaagccgaacgcgcccagttactaccgtg
gaccgcgacgctgaaacgtcactgtgtgcgggtgatcccgtgggagatca
ccggccgccacttcaggttcggtccggaaccggaccgcagccagaccttt
gcctgcgaggcctcgtcacacaaccagcga Rv3130c 84
atgaatcacctaacgacacttgacgccgggtttctcaaggcagaagacgt
ggatcggcacgtgagtctggcaatcggcgctctggcggtcatcgaggggc
cggctcccgatcaggaagccttcttatcgtcgctcgctcaacgcctacgt
ccctgtacccggttcgggcagcggttacgcctgcgcccgttcgacctcgg
tgcacccaaatgggtggacgatcccgacttcgatcttggccgtcatgtgt
ggcgcatcgccttgccgcggcctggcaacgaagaccagttattcgagctg
atcgccgatctgatggcgcgtcgtttggaccggggtcgaccgctgtggga
ggtctgggtcatcgaaggcctggcggacagcaagtgggcgatcctgacca
aactgcaccactgcatggccgacggaatcgcggcgactcacctgctagct
gggctctccgatgaaagtatgagcgacagcttcgcgagcaacatccacac
gaccatgcagtcgcaatccgcatctgtgcggcggggtggattccgtgtca
atccaagcgaggcgttgaccgcgtcgaccgccgtgatggcaggcatcgtt
cgcgcggccaagggtgccagtgagatcgcggccggcgtgctaagtcccgc
cgcgtcgtcgttgaacgggccgatcagtgatttgcgtcgctacagcgcag
caaaggtccctctcgccgacgtcgaacaggtgtgccggaaattcgacgtc
accatcaatgatgttgcgcttgccgcgattacggaaagctaccgcaacgt
cctcatccagcggggtgagcggcctaggtttgattcgctgcgtacgctag
tgccggtctcgacgcgttccaacagcgctttgagcaagaccgataaccgt
gtttcgttaatgctgcccaacctgccggtggatcaagagaacccgctgca
gcggctgcggatcgtgcactcgcggctgactcgggccaaggcggggggac
agagacaattcggaaatactttgatggcgattgccaaccgccttccgttc
cccatgaccgcatgggcggtcgggctgttgatgcggctgccgcagcgtgg
tgttgtcaccgtggcgacaaatgtgccgggtccacgacggccgctgcaga
ttatgggcagacgggtgcttgacctatacccggtttcgccgatcgcgatg
caactgcgcaccagtgtcgcgatgctcagctacgccgacgacctgtactt
cgggatcctggccgactacgacgtggtagcagatgccggccagctggcgc
gaggaattgaagacgccgtcgcacggctggtggcgatcagtaagcggcgc
aaggtgactcgcaggcgcggagcgctatcgctggttgtg Rv3131 85
atgaacacccatttcccggacgccgaaaccgtgcgaacggttctcaccct
ggccgtccgggccccctccatccacaacacgcagccgtggcggtggcggg
tatgcccgacgagtctggagctgttctctagacccgatatgcagctgcgt
agcaccgatccggacgggcgtgagttgatcctcagctgtggtgtggcatt
gcaccactgcgtcgtcgctttggcgtcgctgggctggcaggccaaggtaa
accgtttccccgatcccaaggaccgctgccatctggccaccatcggggta
caaccgcttgttcccgatcaggccgatgtcgccttggcggcggccatacc
gcggcgacgcaccgatcggcgcgcctacagttgctggccggtgccaggag
gtgacatcgcgttgatggccgcaagagcagcccgtggcggggtcatgctg
cggcaggtcagtgccctagaccgaatgaaagccattgtggcgcaggctgt
cttggaccacgtgaccgacgaggaatatctgcgcgagctcaccatttgga
gtgggcgctacggttcagtggccggggttcccgcccgcaacgagccgcca
tcagaccccagtgccccgatccccggtcgcctgttcgccgggcccggtct
gtctcagccgtccgacgtcttacccgctgacgacggcgccgcgatcctgg
cactaggcaccgagacagacgaccggttggcccggctgcgcgccggcgag
gccgccagcatcgtcttgttgaccgcgacggcaatggggctggcgtgctg
cccgatcaccgaaccgctggagatcgccaagacccgcgacgcggtccgtg
ccgaggtgttcggcgccggcggctacccccagatgctgctgcgagtgggt
tgggcaccgatcaatgccgacccgttgccaccgacgccacggcgcgaact
gtcccaggtcgttgagtggccggaagagctactgcgacaacggtgc Rv3132c 86
atgacaacagggggcctcgtcgacgaaaacgacggcgccgcaatgcgtcc
actgcgtcacacgctctcccaactacgcctgcacgagctgctggtcgagg
tgcaggaccgggtcgagcagatcgtcgagggccgggaccgcctcgatggt
ctggtggaggccatgctcgtggtcacagcgggcctggacctggaggcaac
cctacgcgctatcgtgcattcagcgaccagccttgtcgatgcgcgctatg
gcgctatggaggtgcacgaccggcagcatcgggtattgcactttgtctat
gaaggcatcgacgaggagaccgttcggcggatcggccacctaccgaaagg
cctaggcgtcatcgggctgctcatcgaagatcccaaaccgttacggctgg
acgatgtttctgcgcacccggcctcgattggttttccgccgtatcatccg
ccgatgcgtaccttcctcggggtaccggttcgggtgcgcgatgaatcgtt
cggcactctgtacctgactgacaagaccaacgggcaaccgttcagcgacg
acgacgaggttctggtccaggcgctggcggccgccgcgggtatcgcagtc
gcgaatgcccggctctaccagcaggctaaggcgcgtcagtcgtggatcga
ggccacccgtgacatcgccaccgagttgttgtccggcaccgaacccgcga
cggtgttccggcttgtcgccgcggaggcgctcaagctgacggcggctgac
gctgccctggtagccgttcccgtcgacgaggacatgcctgccgctgacgt
gggggagctgctggtgattgaaacagtcggcagcgctgtggcttccattg
ttgggcgaacgattccggtggcgggcgcggtgctgcgggaggtcttcgtc
aacggcattccgcgacgggtcgaccgggtcgatttggaaggcctggacga
actggccgacgcaggtccggcgctgctgttgccgctgcgggccagaggta
ccgtagcgggtgtcgttgttgtgctgagtcaaggcggtccaggggctttc
accgacgaacaactcgagatgatggccgcgttcgccgaccaggccgcgct
ggcttggcaattggccacttcgcaacgtcggatgcgcgaactcgacgtac
tgaccgaccgggatcgtatcgcccgtgacctccatgaccatgtcatccat
cggctcttcgcgattggcctggctttgcagggtgctgtcccgcacgaacg
taatcctgaagtgcagcaacgactctcggacgtggtagacgatctgcaag
acgttatacaggaaatccggaccaccatttatgacctgcacggagcatcg
cagggtatcactcggctccggcagcgaatcgatgcggccgtagcccaatt
tgccgactcggggttgcgcaccagcgttcaattcgtgggtccattgtcgg
tggtcgacagcgcgctcgccgatcaggccgaggcggtggttcgggaagcg
gtcagcaacgcggttcgccatgcgaaggccagcacgttgaccgtccgggt
caaagtcgacgacgacttgtgcatcgaggtgaccgacaacggccgcgggc
tgcccgacgagttcaccggaagcggcttaacgaacctgcggcagcgggca
gagcaggccggcggcgaattcaccctcgcgagcgtaccgggcgcgagcgg
aacagtgctgcgatggtcagcaccgttgtcgcag Rv3134c 87
atgagcgatcctcggccagctcgggcagtggtcgttggtatcgacgggtc
aagggcggcaacgcatgcggcgttgtgggcggtcgatgaggcggtgaacc
gagacattccgctgcgactggtgtacgtcatcgatccgtcccaactgtcc
gccgccggcgagggcggtgggcaatcagcggcccgagcggcgctgcacga
cgcctctcggaaggtcgaggccaccgggcaaccggtcaagatcgaaacgg
aggttctgtgcggcaggccgctcaccaagctgatgcaggagtccaggtcc
gcggcgatgctgtgcgtcggttcggtggggcttgatcatgtccgcggtcg
ccggggttcggtcgcggcgaccctggctgggtcggccttatgccccgtgg
cggtgattcacccgtcgccggccgagccagcgacaacctcccaggtcagc
gcggttgtcgcggaggtggacaatggtgtggtgctgcggcacgcattcga
ggaggccaggctgcgcggagttccgctgcgggccgtggctgtccacgctg
ctgaaacacccgatgacgtcgaacagggcagccggttggcgcatgtacac
ctgagccgtcggctcgcccactggacccggctctaccccgaggtgcgggt
ggatcgggccatcgccggcggcagtgcgtgccgtcatctggccgccaacg
caaagccgggtcagctgttcgtcgcggactcacactccgcgcacgaattg
tgcggtgcataccagcccggatgcgccgtacttacggtacgcagtgccaa cttg Rv3841 88
atgacagaatacgaagggcctaagacaaaattccacgcgttaatgcagga
acagattcataacgaattcacagcggcacaacaatatgtcgcgatcgcgg
tttatttcgacagcgaagacctgccgcagttggcgaagcatttttacagc
caagcggtcgaggaacgaaaccatgcaatgatgctcgtgcaacacctgct
cgaccgcgaccttcgtgtcgaaattcccggcgtagacacggtgcgaaacc
agttcgacagaccccgcgaggcactggcgctggcgctcgatcaggaacgc
acagtcaccgaccaggtcggtcggctgacagcggtggcccgcgacgaggg
cgatttcctcggcgagcagttcatgcagtggttcttgcaggaacagatcg
aagaggtggccttgatggcaaccctggtgcgggttgccgatcgggccggg
gccaacctgttcgagctagagaacttcgtcgcacgtgaagtggatgtggc
gccggccgcatcaggcgccccgcacgctgccgggggccgcctc Rv3842c 89
atgacatgggccgacgaggtgctcgccggacatccctttgtggttgctca
ccgtggtgcgtcggcggctcggccggagcatacccttgccgcctacgacc
tggcgctcaaagagggcgccgacggcgtggaatgtgatgtgcggttgacc
cgggacgggcatctggtctgtgtgcatgaccgccgcctggaccgaacctc
gacgggagccggcttggtcagcacgatgacgctggcccagctacgcgagc
tggagtacggcgcgtggcacgacagctggcgccccgacggttcgcacggc
gacaccagtctgctgaccctggacgcgcttgtttcgctggttttggactg
gcaccggccggtgaagatcttcgtcgagaccaagcatcccgtccgatacg
gctcgctggtggaaaacaagctgctggcgctgctacaccggttcggtatt
gccgcacccgcctccgcagatcgatcccgtgcggtggtgatgtcgttttc
ggccgccgcggtctggcggatccggcgggctgcaccgctgctgccgacgg
tgttgctcggcaagaccccccgatacctgaccagcagtgcggccacggcg
gtcggggcaaccgccgtgggaccctcactgcctgcgttaaaggaatatcc
gcaactcgttgaccgctcggcagctcagggccgggcggtgtactgctgga
acgtcgatgagtacgaggacatcgacttttgccgggaggtcggggtggcc
tggattggtactcaccaccccggccgcaccaaggcctggctggaagacgg
gcgggcgaacgggaccactcgc Rv3908 90
gtgtccgacggcgaacaagccaaatcacgtcgacgccgggggcggcgccg
cgggcggcgcgctgcggctacagccgagaatcacatggacgcccaaccgg
ccggcgacgccaccccgaccccggcaacggcgaagcggtcccggtcccgc
tcacctcgtcgcgggtcgactcggatgcgcaccgtgcacgaaacatcggc
tggagggttggtcattgacggtatcgacggtccacgagacgcgcaggtcg
cggctctgatcggccgcgtcgaccggcgcggccggctgctgtggtcgcta
cccaaggggcacatcgagttgggcgagaccgccgagcagaccgccatccg
cgaggtcgccgaggagaccggcatccgcggcagtgtgctcgccgcgctgg
ggcgcatcgactactggttcgtcaccgacggccggcgggtgcacaagacc
gtccaccattatttgatgcggtttttaggcggagagctgtccgacgaaga
cctcgaggtagccgaggtagcctgggtgccgatccgggaactgccgtctc
gactggcctacgccgacgaacgtcgactagccgaggtggccgacgaactg
atcgacaagctgcagagcgacggccccgccgcgcttccgccgctaccacc
cagctcgcctcgtcgacggccgcaaacgcattcacgcgctcgtcatgccg
atgactcagcaccgggtcagcacaacggtcccgggccggggccg
[0030] Preferably the immunogenic portions are selected from the
group consisting of the sequences presented in Table 1 and the
nucleic acid sequences are selected from the sequences presented in
Table 2.
[0031] In another embodiment, the vaccine is a multiphase vaccine,
where the polypeptides or fragments hereof are fused to other
antigens with efficacy as prophylactic vaccines, where the fusion
partner is selected from e.g. the group consisting of ESAT-6,
TB10.4, CFP10, RD1-ORF5, RD1-ORF2, Rv1036, MPB64, MPT64, Ag85A,
Ag85B (MPT59), MPB59, Ag85C, 19 kDa lipoprotein, MPT32.
[0032] The invention further discloses a therapeutic vaccine
against tuberculosis comprising one or more polypeptides or
fragments hereof, which polypeptides are expressed during the
latent stage of the mycobacteria infection, which stage is
characterized by low-oxygen tension in the microenvironment of the
mycobacteria, or nucleic acids encoding these polypeptides.
[0033] Preferably, the therapeutic and multiphase vaccine comprises
an additional delivery system selected from among, live recombinant
vaccines, that is gene-modified organisms such as bacteria or
viruses expressing mycobacteria genes, or immunogenic delivery
systems such as, DNA vaccines, that is plasmids expressing genes or
gene fragments for the proteins described above, or protein
vaccines, that is the proteins themselves or synthetic peptides
derived from the proteins themselves delivered in a delivery system
such as an adjuvant.
[0034] The invention further discloses a therapeutic vaccine in
which the amino acid sequence is lipidated so as to allow a
self-adjuvanting effect of the polypeptide.
[0035] The invention also discloses a method for treating an
animal, including a human being, with tuberculosis caused by
virulent mycobacteria, e.g., by Mycobacterium tuberculosis,
Mycobacterium africanum or Mycobacterium bovis, comprising
administering to the animal the above-mentioned vaccine.
[0036] The invention also discloses a method for immunizing an
animal, including a human being, against tuberculosis caused by
virulent mycobacteria, e.g., by Mycobacterium tuberculosis,
Mycobacterium africanum or Mycobacterium bovis, comprising
administering to the animal the above mentioned vaccine.
[0037] In a still further embodiment, the invention discloses an
immunogenic composition comprising a polypeptide as defined above,
preferably in the form of a vaccine or in the form of a diagnostic
reagent. The diagnostic reagent can be in the form of a skin test
reagent (administered by the transcutaneous, subcutaneous or
intradermal routes), a serological reagent or a reagent for
stimulating a cell-mediated reaction.
[0038] In another embodiment, the invention discloses a nucleic
acid fragment in isolated form which [0039] (a) comprises a nucleic
acid sequence which encodes a polypeptide as defined above, or
comprises a nucleic acid sequence complementary thereto; or [0040]
(b) has a length of at least 10 nucleotides and hybridizes readily
under stringent hybridization conditions with a nucleotide sequence
selected from the nucleotide sequences presented in Table 2 or a
sequence complementary thereto, or with a nucleotide sequence
selected from a sequence in (a)
[0041] The nucleic acid fragment is preferably a DNA fragment. The
fragment can be used as a pharmaceutical.
[0042] In another embodiment, the invention discloses a vaccine
comprising a nucleic acid fragment according to the invention,
optionally inserted in a vector, the vaccine effecting in vivo
expression of antigen by a human being or other mammal or animal,
to whom the vaccine has been administered, the amount of expressed
antigen being effective to confer substantially increased
resistance to tuberculosis caused by virulent mycobacteria, e.g. by
Mycobacterium tuberculosis, Mycobacterium africanum or
Mycobacterium bovis, in an animal, including a human being.
[0043] In a further embodiment, the invention discloses the use of
a nucleic acid fragment according to the invention for the
preparation of a composition for the diagnosis of tuberculosis
caused by virulent mycobacteria, e.g., by Mycobacterium
tuberculosis, Mycobacterium africanum or Mycobacterium bovis, and
the use of a nucleic acid fragment according to the invention for
the preparation of a pharmaceutical composition for the vaccination
against tuberculosis caused by virulent mycobacteria, e.g., by
Mycobacterium tuberculosis, Mycobacterium africanum or
Mycobacterium bovis.
[0044] In a still further embodiment, the invention discloses a
vaccine for immunizing an human being or other mammal or animal,
against tuberculosis caused by virulent mycobacteria, e.g. by
Mycobacterium tuberculosis, Mycobacterium africanum or
Mycobacterium bovis, comprising as the effective component a
non-pathogenic microorganism, wherein at least one copy of a DNA
fragment comprising a DNA sequence encoding a polypeptide as
defined above has been incorporated into the microorganism (e.g.,
placed on a plasmid or in the genome) in a manner allowing the
microorganism to express and optionally secrete the
polypeptide.
[0045] In another embodiment, the invention discloses a replicable
expression vector, which comprises a nucleic acid fragment
according to the invention, and a transformed cell harboring at
least one such vector.
[0046] In another embodiment, the invention discloses a method for
producing a polypeptide as defined above, comprising [0047] (a)
inserting a nucleic acid fragment according to the invention into a
vector that is able to replicate in a host cell, introducing the
resulting recombinant vector into the host cell, culturing the host
cell in a culture medium under conditions sufficient to effect
expression of the polypeptide, and recovering the polypeptide from
the host cell or culture medium; [0048] (b) isolating the
polypeptide from a whole mycobacterium, e.g. Mycobacterium
tuberculosis, Mycobacterium africanum or Mycobacterium bovis, from
culture filtrate or from lysates or fractions thereof; or [0049]
(c) synthesizing the polypeptide e.g. by solid or liquid phase
peptide synthesis.
[0050] The invention also discloses a method of diagnosing
tuberculosis caused by virulent mycobacteria, e.g. by Mycobacterium
tuberculosis, Mycobacterium africanum or Mycobacterium bovis, in an
animal, including a human being, comprising intradermally
injecting, in the animal, a polypeptide as defined above or an
immunogenic composition as defined above, a positive skin response
at the location of injection being indicative of the animal having
tuberculosis, and a negative skin response at the location of
injection being indicative of the animal not having
tuberculosis.
[0051] In another embodiment, the invention discloses a method for
immunizing an animal, including a human being, against tuberculosis
caused by virulent mycobacteria, e.g. by Mycobacterium
tuberculosis, Mycobacterium africanum or Mycobacterium bovis,
comprising administering to the animal the polypeptide as defined
above, the immunogenic composition according to the invention, or
the vaccine according to the invention.
[0052] Another embodiment of the invention discloses a monoclonal
or polyclonal antibody, which is specifically reacting with a
polypeptide as defined above in an immuno assay, or a specific
binding fragment of said antibody. Preferably, said antibody is for
use as a diagnostic reagent, e.g. for detection of mycobacteria
antigens in sputum, urine or other body fluids of an infected
animal, including a human being.
[0053] In a further embodiment the invention discloses a
pharmaceutical composition that comprises an immunologically
responsive amount of at least one member selected from the group
consisting of: [0054] (a) a polypeptide selected from the sequences
presented in Table 1, or an immunogenic portion thereof; [0055] (b)
an amino acid sequence which has a sequence identity of at least
70% to any one of said polypeptides in (a) and is immunogenic;
[0056] (c) a fusion polypeptide comprising at least one polypeptide
or amino acid sequence according to (a) or (b) and at least one
fusion partner; [0057] (d) a nucleic acid sequence which encodes a
polypeptide or amino acid sequence according to (a), (b) or (c);
[0058] (e) a nucleic acid sequence which is complementary to a
sequence according to (d); [0059] (f) a nucleic acid sequence which
has a length of at least 10 nucleotides and which hybridizes under
stringent conditions with a nucleic acid sequence according to (d)
or (e); and [0060] (g) a non-pathogenic micro-organism which has
incorporated (e.g. placed on a plasmid or in the genome) therein a
nucleic acid sequence according to (d), (e) or (f) in a manner to
permit expression of a polypeptide encoded thereby.
[0061] In a still further embodiment the invention discloses a
method for stimulating an immunogenic response in an animal which
comprises administering to said animal an immunologically
stimulating amount of at least one member selected from the group
consisting of: [0062] (a) a polypeptide selected from the sequences
presented in Table 1, or an immunogenic portion thereof; [0063] (b)
an amino acid sequence which has a sequence identity of at least
70% to any one of said polypeptides in (a) and is immunogenic;
[0064] (c) a fusion polypeptide comprising at least one polypeptide
or amino acid sequence according to (a) or (b) and at least one
fusion partner; [0065] (d) a nucleic acid sequence which encodes a
polypeptide or amino acid sequence according to (a), (b) or (c);
[0066] (e) a nucleic acid sequence that is complementary to a
sequence according to (d); [0067] (f) a nucleic acid sequence which
has a length of at least 10 nucleotides and which hybridizes under
stringent conditions with a nucleic acid sequence according to (d)
or (e); and [0068] (g) a non-pathogenic micro-organism which has
incorporated therein (e.g. placed on a plasmid or in the genome) a
nucleic acid sequence according to (d), (e) or (f) in a manner to
permit expression of a polypeptide encoded thereby.
[0069] The vaccine, immunogenic composition and pharmaceutical
composition according to the invention can be used therapeutically
in a subject infected with a virulent mycobacterium combined with a
prophylactic composition in a subject to prevent further infection
with a virulent mycobacterium.
[0070] The invention also discloses a method for diagnosing
previous or ongoing infection with a virulent mycobacterium, said
method comprising [0071] (a) contacting a sample, e.g. a blood
sample, with a composition comprising an antibody according to the
invention, a nucleic acid fragment according to the invention
and/or a polypeptide as defined above, or [0072] (b) contacting a
sample, e.g. a blood sample comprising mononuclear cells (e.g.
T-lymphocytes), with a composition comprising one or more
polypeptides as defined above in order to detect a positive
reaction, e.g. proliferation of the cells or release of cytokines
such as IFN-.gamma..
[0073] Finally, the invention discloses a method of diagnosing
Mycobacterium tuberculosis infection in a subject comprising:
[0074] (a) contacting a polypeptide as defined above with a bodily
fluid of the subject; [0075] (b) detecting binding of a antibody to
said polypeptide, said binding being an indication that said
subject is infected by Mycobacterium tuberculosis or is susceptible
to Mycobacterium tuberculosis infection.
DEFINITIONS
Polypeptides
[0076] The word "polypeptide" in the present invention should have
its usual meaning. That is an amino acid chain of any length,
including a full-length protein, oligopeptides, short peptides and
fragments thereof, wherein the amino acid residues are linked by
covalent peptide bonds.
[0077] The polypeptide may be chemically modified by being
glycosylated, by being lipidated (e.g. by chemical lipidation with
palmitoyloxy succinimide as described by Mowat et al. 1991 or with
dodecanoyl chloride as described by Lustig et al. 1976), by
comprising prosthetic groups, or by containing additional amino
acids such as e.g. a his-tag or a signal peptide.
[0078] Each polypeptide may thus be characterized by specific amino
acids and be encoded by specific nucleic acid sequences. It will be
understood that such sequences include analogues and variants
produced by recombinant or synthetic methods wherein such
polypeptide sequences have been modified by substitution,
insertion, addition or deletion of one or more amino acid residues
in the recombinant polypeptide and still be immunogenic in any of
the biological assays described herein. Substitutions are
preferably "conservative". These are defined according to the
following table. Amino acids in the same block in the second column
and preferably in the same line in the third column may be
substituted for each other. The amino acids in the third column are
indicated in one-letter code.
TABLE-US-00003 ALIPHATIC Non-polar GAP ILV Polar-uncharged CSTM NQ
Polar-charged DE KR AROMATIC HFWY
[0079] A preferred polypeptide within the present invention is an
immunogenic antigen from M. tuberculosis produced when the organism
is subjected to the stresses associated with latent infection. Such
antigen can for example also be derived from the M. tuberculosis
cell and/or M. tuberculosis culture filtrate. Thus, a polypeptide
comprising an immunogenic portion of one of the above antigens may
consist entirely of the immunogenic portion, or may contain
additional sequences. The additional sequences may be derived from
the native M. tuberculosis antigen or be heterologous and such
sequences may, but need not, be immunogenic.
[0080] Each polypeptide is encoded by a specific nucleic acid
sequence. It will be understood that such sequences include
analogues and variants hereof wherein such nucleic acid sequences
have been modified by substitution, insertion, addition or deletion
of one or more nucleic acids. Substitutions are preferably silent
substitutions in the codon usage that will not lead to any change
in the amino acid sequence, but may be introduced to enhance the
expression of the protein.
[0081] In the present context the term "substantially pure
polypeptide fragment" means a polypeptide preparation which
contains at most 5% by weight of other polypeptide material with
which it is natively associated (lower percentages of other
polypeptide material are preferred, e.g. at most 4%, at most 3%, at
most 2%, at most 1%, and at most 1/2%). It is preferred that the
substantially pure polypeptide is at least 96% pure, i.e. that the
polypeptide constitutes at least 96% by weight of total polypeptide
material present in the preparation, and higher percentages are
preferred, such as at least 97%, at least 98%, at least 99%, at
least 99.25%, at least 99.5%, and at least 99.75%. It is especially
preferred that the polypeptide fragment is in "essentially pure
form", i.e. that the polypeptide fragment is essentially free of
any other antigen with which it is natively associated, i.e. free
of any other antigen from bacteria belonging to the tuberculosis
complex or a virulent mycobacterium. This can be accomplished by
preparing the polypeptide fragment by means of recombinant methods
in a non-mycobacterial host cell as will be described in detail
below, or by synthesizing the polypeptide fragment by the
well-known methods of solid or liquid phase peptide synthesis, e.g.
by the method described by Merrifield, 1963, or variations
thereof.
[0082] By the term "virulent mycobacterium" is understood a
bacterium capable of causing the tuberculosis disease in an animal
or in a human being. Examples of virulent mycobacteria include but
are not limited to M. tuberculosis, M. africanum, and M. bovis.
Examples of relevant animals are cattle, possums, badgers and
kangaroos.
[0083] By "a TB patient" is understood an individual with culture
or microscopically proven infection with virulent mycobacteria,
and/or an individual clinically diagnosed with TB and who is
responsive to anti-TB chemotherapy. Culture, microscopy and
clinical diagnosis of TB are well known by any person skilled in
the art.
[0084] By the term "PPD-positive individual" is understood an
individual with a positive Mantoux test or an individual where PPD
induces a positive in vitro recall response determined by release
of IFN-.gamma..
[0085] By "a latently infected individual" is understood an
individual, who has been infected by a virulent mycobacterium, e.g.
M. tuberculosis, but shows no sign of active tuberculosis. It is
likely that individuals who have been vaccinated, e.g. by BCG, or
treated for TB may still retain the mycobacteria within their
bodies, although this is currently impossible to prove since such
individuals would be expected to be positive if tested for PPD
reactivity. Nonetheless, in its most accurate sense,
"latently-infected" may be used to describe any individual who has
M. tuberculosis residing in their tissues but who is not clinically
ill.
[0086] By the term "delayed type hypersensitivity reaction" (DTH)
is understood a T-cell mediated inflammatory response elicited
after the injection of a polypeptide into, or application to, the
skin, said inflammatory response appearing 72-96 hours after the
polypeptide injection or application.
[0087] By the term "IFN-.gamma." is understood interferon-gamma.
The measurement of IFN-.gamma. is used as an indication of an
immunological response.
[0088] By the terms "nucleic acid fragment" and "nucleic acid
sequence" are understood any nucleic acid molecule including DNA,
RNA, LNA (locked nucleic acids), PNA, RNA, dsRNA and
RNA-DNA-hybrids. Also included are nucleic acid molecules
comprising non-naturally occurring nucleosides. The term includes
nucleic acid molecules of any length e.g. from 10 to 10000
nucleotides, depending on the use. When the nucleic acid molecule
is for use as a pharmaceutical, e.g. in DNA therapy, or for use in
a method for producing a polypeptide according to the invention, a
molecule encoding at least one epitope is preferably used, having a
length from about 18 to about 1000 nucleotides, the molecule being
optionally inserted into a vector. When the nucleic acid molecule
is used as a probe, as a primer or in antisense therapy, a molecule
having a length of 10-100 is preferably used. According to the
invention, other molecule lengths can be used, for instance a
molecule having at least 12, 15, 21, 24, 27, 30, 33, 36, 39, 42,
50, 60, 70, 80, 90, 100, 200, 300, 400, 500 or 1000 nucleotides (or
nucleotide derivatives), or a molecule having at most 10000, 5000,
4000, 3000, 2000, 1000, 700, 500, 400, 300, 200, 100, 50, 40, 30 or
20 nucleotides (or nucleotide derivatives).
[0089] The term "stringent" when used in conjunction with
hybridization conditions is as defined in the art, i.e. the
hybridization is performed at a temperature not more than
15-20.degree. C. under the melting point T.sub.m, cf. Sambrook et
al, 1989, pages 11.45-11.49. Preferably, the conditions are "highly
stringent", i.e. 5-10.degree. C. under the melting point
T.sub.m.
[0090] Throughout this specification, unless the context requires
otherwise, the word "comprise", or variations thereof such as
"comprises" or "comprising", will be understood to imply the
inclusion of a stated element or integer or group of elements or
integers but not the exclusion of any other element or integer or
group of elements or integers.
Sequence Identity
[0091] The term "sequence identity" indicates a quantitative
measure of the degree of homology between two amino acid sequences
of equal length or between two nucleotide sequences of equal
length. The two sequences to be compared must be aligned to best
possible fit allowing the insertion of gaps or alternatively,
truncation at the ends of the protein sequences. The sequence
identity can be calculated as
( N ref - N dif ) 100 N ref , ##EQU00001##
wherein N.sub.dif is the total number of non-identical residues in
the two sequences when aligned and wherein N.sub.ref is the number
of residues in one of the sequences. Hence, the DNA sequence
AGTCAGTC [SEQ ID NO: 184] will have a sequence identity of 75% with
the sequence AATCAATC, SEQ ID NO: 185 (N.sub.dif=2 and
N.sub.ref=8). A gap is counted as non-identity of the specific
residue(s), i.e. the DNA sequence AGTGTC [SEQ ID NO: 186] will have
a sequence identity of 75% with the DNA sequence AGTCAGTC, SEQ ID
NO: 187, (N.sub.dif=2 and N.sub.ref=8). Sequence identity can
alternatively be calculated by the BLAST program e.g. the BLASTP
program (Pearson, 1988, or online through the NIH website). In one
aspect of the invention, alignment is performed with the sequence
alignment method ClustalW with default parameters as described by
Thompson J., et al. 1994 and as available through online
sources.
[0092] A preferred minimum percentage of sequence identity is at
least 80%, such as at least 85%, at least 90%, at least 91%, at
least 92%, at least 93%, at least 94%, at least 95%, at least 96%,
at least 97%, at least 98%, at least 99%, and at least 99.5%.
Immunogenic Portion
[0093] In a preferred embodiment of the invention, the polypeptide
comprises an immunogenic portion of the polypeptide, such as an
epitope for a B-cell or T-cell. The immunogenic portion of a
polypeptide is a part of the polypeptide, which elicits an immune
response in an animal or a human being, and/or in a biological
sample determined by any of the biological assays described herein.
The immunogenic portion of a polypeptide may be a T-cell epitope or
a B-cell epitope. Immunogenic portions can be related to one or a
few relatively small parts of the polypeptide, they can be
scattered throughout the polypeptide sequence or be situated in
specific parts of the polypeptide. For a few polypeptides, epitopes
have even been demonstrated to be scattered throughout the
polypeptide covering the full sequence (Ravn et al 1999). In order
to identify relevant T-cell epitopes which are recognized during an
immune response, it is possible to use overlapping oligopeptides
for the detection of MHC class II epitopes, preferably synthetic,
having a length of e.g. 20 amino acid residues derived from the
polypeptide. These peptides can be tested in biological assays
(e.g. the IFN-.gamma. assay as described herein) and some of these
will give a positive response (and thereby be immunogenic) as
evidence for the presence of a T cell epitope in the peptide. For
the detection of MHC class I epitopes it is possible to predict
peptides that will bind (Stryhn et al. 1996) and hereafter produce
these peptides synthetic and test them in relevant biological
assays, e.g. the IFN-.gamma. assay as described herein. The
peptides preferably having a length of, e.g., 8 to 11 amino acid
residues derived from the polypeptide. B-cell epitopes can be
determined by analyzing the B cell recognition to overlapping
peptides covering the polypeptide of interest as, e.g., described
in Harboe et al 1998.
[0094] Although the minimum length of a T-cell epitope has been
shown to be at least 6 amino acids, it is normal that such epitopes
are constituted of longer stretches of amino acids. Hence, it is
preferred that the polypeptide fragment of the invention has a
length of at least 7 amino acid residues, such as at least 8, at
least 9, at least 10, at least 12, at least 14, at least 16, at
least 18, at least 20, at least 22, at least 24, and at least 30
amino acid residues. Hence, in important embodiments of the
inventive method, it is preferred that the polypeptide fragment has
a length of at most 50 amino acid residues, such as at most 40, 35,
30, 25, and 20 amino acid residues. It is expected that the
peptides having a length of from 10 to 20 amino acid residues will
prove to be most efficient as MHC class II epitopes and therefore
especially preferred lengths of the polypeptide fragment used in
the inventive method are 18, such as 15, 14, 13, 12 and even 11
amino acid residues. It is expected that the peptides having a
length of from 7 to 12 amino acid residues will prove to be most
efficient as MHC class I epitopes and therefore especially
preferred lengths of the polypeptide fragment used in the inventive
method are 11, such as 10, 9, 8 and even 7 amino acid residues.
[0095] Immunogenic portions of polypeptides may be recognized by a
broad part (high frequency) or by a minor part (low frequency) of
the genetically heterogeneous human population. In addition some
immunogenic portions induce high immunological responses
(dominant), whereas others induce lower, but still significant,
responses (subdominant). High frequency or low frequency can be
related to the immunogenic portion binding to widely distributed
MHC molecules (HLA type) or even by multiple MHC molecules
(Sinigaglia, 1988, Kilgus, 1991).
[0096] In the context of providing candidate molecules for a new
vaccine against tuberculosis, the subdominant epitopes are however
as relevant as are the dominant epitopes since it has been shown
(Olsen, 2000) that such epitopes can induce protection regardless
of the fact that they are not as strongly or broadly
recognized.
Variants
[0097] A common feature of the polypeptides of the invention is
their capability to induce an immunological response as illustrated
in the examples. It is understood that a variant of a polypeptide
of the invention produced by substitution, insertion, addition or
deletion may also be immunogenic as determined by any of the assays
described herein.
Immune Individual
[0098] An immune individual is defined as a person or an animal,
which has cleared or controlled an infection with virulent
mycobacteria or has received a vaccination with M. bovis BCG.
Immune Response
[0099] The immune response may be monitored by one of the following
methods: [0100] An in vitro cellular response is determined by
induction of the release of a relevant cytokine such as IFN-.gamma.
from, or the induction of proliferation in lymphocytes withdrawn
from an animal or human being currently or previously infected with
virulent mycobacteria or immunized with the relevant polypeptide.
The induction being performed by the addition of the polypeptide or
the immunogenic portion of the polypeptide to a suspension
comprising from 2.times.10.sup.5 cells to 4.times.10.sup.5 cells
per well. The cells being isolated from either the blood, the
spleen, the liver or the lung and the addition of the polypeptide
or the immunogenic portion resulting in a concentration of not more
than 20 .mu.g per ml suspension and the stimulation being performed
from two to five days. For monitoring cell proliferation the cells
are pulsed with radioactive labeled Thymidine and after 16-22 hours
of incubation detecting the proliferation by liquid scintillation
counting. A positive response is defined as being a response more
than background plus two standard deviations. The release of
IFN-.gamma. can be determined by the ELISA method, which is well
known to a person skilled in the art. A positive response being a
response more than background plus two standard deviations. Other
cytokines than IFN-.gamma. could be relevant when monitoring the
immunological response to the polypeptide, such as IL-12,
TNF-.alpha., IL-4, IL-5, IL-10, IL-6, TGF-.beta.. Another and more
sensitive method for detecting the immune response is the ELISpot
method, in which the frequency of IFN-.gamma. producing cells is
determined. In an ELIspot plate (MAHA, Millipore) precoated with
anti-murine IFN-.gamma. antibodies (PharMingen) graded numbers of
cells isolated from either blood, spleen, or lung (typically
between 1 to 4.times.10.sup.5 cells/well) are incubated for 24-32
hrs in the presence of the polypeptide or the immunogenic portion
resulting in a concentration of not more than 20 .mu.g per ml. The
plates are subsequently incubated with biotinylated
anti-IFN-.gamma. antibodies followed by a streptavidin-alkaline
phosphatase incubation. The IFN-.gamma. producing cells are
identified by adding BCIP/NBT (Sigma), the relevant substrate
giving rise to spots. These spots can be enumerated using a
dissection microscope. It is also a possibility to determine the
presence of mRNA coding for the relevant cytokine by the use of the
PCR technique. Usually one or more cytokines will be measured
utilizing for example PCR, ELISPOT or ELISA. It will be appreciated
by a person skilled in the art that a significant increase or
decrease in the amount of any of these cytokines induced by a
specific polypeptide can be used in evaluation of the immunological
activity of the polypeptide. [0101] An in vitro cellular response
may also be determined by the use of T cell lines derived from an
immune individual or an M. tuberculosis-infected person where the T
cell lines have been driven with either live mycobacteria, extracts
from the bacterial cell or culture filtrate for 10 to 20 days with
the addition of IL-2. The induction being performed by addition of
not more than 20 .mu.g polypeptide per ml suspension to the T cell
lines containing from 1.times.10.sup.5 cells to 3.times.10.sup.5
cells per well and incubation being performed from two to six days.
The induction of IFN-.gamma. or release of another relevant
cytokine is detected by ELISA. The stimulation of T cells can also
be monitored by detecting cell proliferation using radioactively
labeled Thymidine as described above. For both assays a positive
response being a response more than background plus two standard
deviations. [0102] An in vivo cellular response may be determined
as a positive DTH response after intradermal injection or local
application patch of at most 100 .mu.g of the polypeptide or the
immunogenic portion to an individual who is clinically or
subclinically infected with a virulent mycobacterium, a positive
response having a diameter of at least 5 mm 72-96 hours after the
injection or application. [0103] An in vitro humoral response is
determined by a specific antibody response in an immune or infected
individual. The presence of antibodies may be determined by an
ELISA technique or a Western blot where the polypeptide or the
immunogenic portion is absorbed to either a nitrocellulose membrane
or a polystyrene surface. The serum is preferably diluted in PBS
from 1:10 to 1:100 and added to the absorbed polypeptide and the
incubation being performed from 1 to 12 hours. By the use of
labeled secondary antibodies the presence of specific antibodies
can be determined by measuring the OD e.g. by ELISA where a
positive response is a response of more than background plus two
standard deviations or alternatively a visual response in a Western
blot. [0104] Another relevant parameter is measurement of the
protection in animal models induced after vaccination with the
polypeptide in an adjuvant or after DNA vaccination. Suitable
animal models include primates, guinea pigs or mice, which are
challenged with an infection of a virulent Mycobacterium. Readout
for induced protection could be decrease of the bacterial load in
target organs compared to non-vaccinated animals, prolonged
survival times compared to non-vaccinated animals and diminished
weight loss compared to non-vaccinated animals.
Preparation Methods
[0105] In general, M. tuberculosis antigens, and DNA sequences
encoding such antigens, may be prepared using any one of a variety
of procedures.
[0106] They may be purified as native proteins from the M.
tuberculosis cell or culture filtrate by procedures such as those
described above. Immunogenic antigens may also be produced
recombinantly using a DNA sequence encoding the antigen, which has
been inserted into an expression vector and expressed in an
appropriate host. Examples of host cells are E. coli. The
polypeptides or immunogenic portion hereof can also be produced
synthetically having fewer than about 100 amino acids, and
generally fewer than 50 amino acids and may be generated using
techniques well known to those ordinarily skilled in the art, such
as commercially available solid-phase techniques where amino acids
are sequentially added to a growing amino acid chain.
[0107] In the construction and preparation of plasmid DNA encoding
the polypeptide as defined for DNA vaccination a host strain such
as E. coli can be used. Plasmid DNA can then be prepared from
cultures of the host strain carrying the plasmid of interest, and
purified using e.g. the Qiagen Giga-Plasmid column kit (Qiagen,
Santa Clarita, Calif., USA) including an endotoxin removal step. It
is preferred that plasmid DNA used for DNA vaccination is endotoxin
free.
Fusion Proteins
[0108] The immunogenic polypeptides may also be produced as fusion
proteins, by which methods superior characteristics of the
polypeptide of the invention can be achieved. For instance, fusion
partners that facilitate export of the polypeptide when produced
recombinantly, fusion partners that facilitate purification of the
polypeptide, and fusion partners which enhance the immunogenicity
of the polypeptide fragment of the invention are all interesting
possibilities. Therefore, the invention also pertains to a fusion
polypeptide comprising at least one polypeptide or immunogenic
portion defined above and at least one fusion partner. The fusion
partner can, in order to enhance immunogenicity, be another
polypeptide derived from M. tuberculosis, such as of a polypeptide
fragment derived from a bacterium belonging to the tuberculosis
complex, such as ESAT-6, TB10.4, CFP10, RD1-ORF5, RD1-ORF2, Rv1036,
MPB64, MPT64, Ag85A, Ag85B (MPT59), MPB59, Ag85C, 19 kDa
lipoprotein, MPT32 and alpha-crystalline, or at least one T-cell
epitope of any of the above mentioned antigens (Skjot et al 2000;
Danish Patent application PA 2000 00666; Danish Patent application
PA 1999 01020; U.S. patent application Ser. No. 09/505,739;
Rosenkrands et al 1998; Nagai et al 1991). The invention also
pertains to a fusion polypeptide comprising mutual fusions of two
or more of the polypeptides (or immunogenic portions thereof) of
the invention.
[0109] Other fusion partners, which could enhance the
immunogenicity of the product, are lymphokines such as IFN-.gamma.,
IL-2 and IL-12. In order to facilitate expression and/or
purification, the fusion partner can e.g. be a bacterial fimbrial
protein, e.g. the pilus components pilin and papA; protein A; the
ZZ-peptide (ZZ-fusions are marketed by Pharmacia in Sweden); the
maltose binding protein; glutathione S-transferase;
.beta.-galactosidase; or poly-histidine. Fusion proteins can be
produced recombinantly in a host cell, which could be E. coli, and
it is a possibility to induce a linker region between the different
fusion partners.
[0110] Other interesting fusion partners are polypeptides, which
are lipidated so that the immunogenic polypeptide is presented in a
suitable manner to the immune system. This effect is e.g. known
from vaccines based on the Borrelia burgdorferi OspA polypeptide as
described in e.g. WO 96/40718 A or vaccines based on the
Pseudomonas aeruginosa OprI lipoprotein (Cote-Sierra J 1998).
Another possibility is N-terminal fusion of a known signal sequence
and an N-terminal cystein to the immunogenic polypeptide. Such a
fusion results in lipidation of the immunogenic polypeptide at the
N-terminal cystein, when produced in a suitable production
host.
Uses
Protein Vaccine
[0111] Another part of the invention pertains to a vaccine
composition comprising a polypeptide (or at least one immunogenic
portion thereof) or fusion polypeptide according to the invention.
In order to ensure optimum performance of such a vaccine
composition it is preferred that it comprises an immunologically
and pharmaceutically acceptable carrier, vehicle or adjuvant.
[0112] An effective vaccine, wherein a polypeptide of the invention
is recognized by the animal, will in an animal model be able to
decrease bacterial load in target organs, prolong survival times
and/or diminish weight loss after challenge with a virulent
Mycobacterium, compared to non-vaccinated animals
[0113] Suitable carriers are selected from the group consisting of
a polymer to which the polypeptide(s) is/are bound by hydrophobic
non-covalent interaction, such as a plastic, e.g. polystyrene, or a
polymer to which the polypeptide(s) is/are covalently bound, such
as a polysaccharide, or a polypeptide, e.g. bovine serum albumin,
ovalbumin or keyhole limpet haemocyanin. Suitable vehicles are
selected from the group consisting of a diluent and a suspending
agent. The adjuvant is preferably selected from the group
consisting of dimethyldioctadecylammonium bromide (DDA), Quil A,
poly I:C, aluminum hydroxide, Freund's incomplete adjuvant,
IFN-.gamma., IL-2, IL-12, monophosphoryl lipid A (MPL), Trehalose
Dimycolate (TDM), Trehalose Dibehenate and muramyl dipeptide
(MDP).
[0114] Preparation of vaccines which contain peptide sequences as
active ingredients is generally well understood in the art, as
exemplified by U.S. Pat. Nos. 4,608,251; 4,601,903; 4,599,231 and
4,599,230, all incorporated herein by reference.
[0115] Other methods of achieving adjuvant effect for the vaccine
include use of agents such as aluminum hydroxide or phosphate
(alum), synthetic polymers of sugars (Carbopol), aggregation of the
protein in the vaccine by heat treatment, aggregation by
reactivating with pepsin treated (Fab) antibodies to albumin,
mixture with bacterial cells such as C. parvum or endotoxins or
lipopolysaccharide components of gram-negative bacteria, emulsion
in physiologically acceptable oil vehicles such as mannide
mono-oleate (Aracel A) or emulsion with 20 percent solution of a
perfluorocarbon (Fluosol-DA) used as a block substitute may also be
employed. Other possibilities involve the use of immune modulating
substances such as cytokines or synthetic IFN-.gamma. inducers such
as poly I:C in combination with the above-mentioned adjuvants.
[0116] Another interesting possibility for achieving adjuvant
effect is to employ the technique described in Gosselin et al.,
1992 (which is hereby incorporated by reference herein). In brief,
a relevant antigen such as an antigen of the present invention can
be conjugated to an antibody (or antigen binding antibody fragment)
against the Fc.gamma. receptors on monocytes/macrophages.
[0117] The vaccines are administered in a manner compatible with
the dosage formulation, and in such amount as will be
therapeutically effective and immunogenic. The quantity to be
administered depends on the subject to be treated, including, e.g.,
the capacity of the individual's immune system to mount an immune
response, and the degree of protection desired. Suitable dosage
ranges are of the order of several hundred micrograms active
ingredient per vaccination with a preferred range from about 0.1
.mu.g to 1000 .mu.g, such as in the range from about 1 .mu.g to 300
.mu.g, and especially in the range from about 10 .mu.g to 50 .mu.g.
Suitable regimens for initial administration and booster shots are
also variable but are typified by an initial administration
followed by subsequent inoculations or other administrations.
[0118] The manner of application may be varied widely. Any of the
conventional methods for administration of a vaccine are
applicable. These are believed to include oral application on a
solid physiologically acceptable base or in a physiologically
acceptable dispersion, parenterally, by injection or the like. The
dosage of the vaccine will depend on the route of administration
and will vary according to the age of the person to be vaccinated
and, to a lesser degree, the size of the person to be
vaccinated.
[0119] The vaccines are conventionally administered parenterally,
by injection, for example, either subcutaneously or
intramuscularly. Additional formulations which are suitable for
other modes of administration include suppositories and, in some
cases, oral formulations. For suppositories, traditional binders
and carriers may include, for example, polyalkylene glycols or
triglycerides; such suppositories may be formed from mixtures
containing the active ingredient in the range of 0.5% to 10%,
preferably 1-2%. Oral formulations include such normally employed
excipients as, for example, pharmaceutical grades of mannitol,
lactose, starch, magnesium stearate, sodium saccharine, cellulose,
magnesium carbonate, and the like. These compositions take the form
of solutions, suspensions, tablets, pills, capsules, sustained
release formulations or powders and advantageously contain 10-95%
of active ingredient, preferably 25-70%.
[0120] In many instances, it will be necessary to have multiple
administrations of the vaccine. Especially, vaccines can be
administered to prevent an infection with virulent mycobacteria, a
prophylactic vaccine, and/or to treat established mycobacterial
infection, a therapeutic vaccine. When administered to prevent an
infection, the vaccine is given prophylactically, before definitive
clinical signs, diagnosis or identification of an infection TB are
present. Since the current vaccine BCG appears to induce an
effective, but short-lived immune response, prophylactic vaccines
may also be designed to be used as booster vaccines. Such booster
vaccines are given to individuals who have previously received a
vaccination, with the intention of prolonging the period of
protection. In instances where the individual has already become
infected or is suspected to have become infected, the previous
vaccination may have provided sufficient immunity to prevent
primary disease, but as discussed previously, boosting this immune
response will not help against the latent infection. In such a
situation, the vaccine will necessarily have to be a therapeutic
vaccine designed for efficacy against the latent stage of
infection. A combination of a prophylactic vaccine and a
therapeutic vaccine, which is active against both primary and
latent infection, constitutes a multiphase vaccine.
[0121] Due to genetic variation, different individuals may react
with immune responses of varying strength to the same polypeptide.
Therefore, the vaccine according to the invention may comprise
several different polypeptides in order to increase the immune
response. The vaccine may comprise two or more polypeptides or
immunogenic portions, where all of the polypeptides are as defined
above, or some but not all of the peptides may be derived from
virulent mycobacteria. In the latter example, the polypeptides not
necessarily fulfilling the criteria set forth above for
polypeptides may either act due to their own immunogenicity or
merely act as adjuvants.
[0122] The vaccine may comprise 1-20, such as 2-20 or even 3-20
different polypeptides or fusion polypeptides, such as 3-10
different polypeptides or fusion polypeptides.
[0123] The invention also pertains to a method for immunizing an
animal, including a human being, against TB caused by virulent
mycobacteria, comprising administering to the animal the
polypeptide of the invention, or a vaccine composition of the
invention as described above, or a living vaccine described
above.
[0124] The invention also pertains to a method for producing an
immunologic composition according to the invention, the method
comprising preparing, synthesizing or isolating a polypeptide
according to the invention, and solubilizing or dispersing the
polypeptide in a medium for a vaccine, and optionally adding other
M. tuberculosis antigens and/or a carrier, vehicle and/or adjuvant
substance.
DNA Vaccine.
[0125] The nucleic acid fragments of the invention may be used for
effecting in vivo expression of antigens, i.e. the nucleic acid
fragments may be used in so-called DNA vaccines as reviewed in
Ulmer et al 1993, which is included by reference.
[0126] Hence, the invention also relates to a vaccine comprising a
nucleic acid fragment according to the invention, the vaccine
effecting in vivo expression of antigen by an animal, including a
human being, to whom the vaccine has been administered, the amount
of expressed antigen being effective to confer substantially
increased resistance to infections caused by virulent mycobacteria
in an animal, including a human being.
[0127] The above mentioned definitions and distinctions of
prophylactic-, booster-, therapeutic- and multiphase vaccines also
applies for DNA vaccines
[0128] The efficacy of such a DNA vaccine can possibly be enhanced
by administering the gene encoding the expression product together
with a DNA fragment encoding a polypeptide that has the capability
of modulating an immune response.
Live Recombinant Vaccines
[0129] One possibility for effectively activating a cellular immune
response for a vaccine can be achieved by expressing the relevant
antigen in a vaccine in a non-pathogenic microorganism or virus.
Well-known examples of such microorganisms are Mycobacterium bovis
BCG, Salmonella and Pseudomona and examples of viruses are Vaccinia
Virus and Adenovirus.
[0130] Therefore, another important aspect of the present invention
is an improvement of the living BCG vaccine presently available,
wherein one or more copies of a DNA sequence encoding one or more
polypeptide as defined above has been incorporated into the genome
of the micro-organism in a manner allowing the micro-organism to
express and secrete the polypeptide. The incorporation of more than
one copy of a nucleotide sequence of the invention is contemplated
to enhance the immune response.
[0131] Another possibility is to integrate the DNA encoding the
polypeptide according to the invention in an attenuated virus such
as the vaccinia virus or Adenovirus (Rolph et al 1997). The
recombinant vaccinia virus is able to replicate within the
cytoplasma of the infected host cell and the polypeptide of
interest can therefore induce an immune response, which is
envisioned to induce protection against TB.
Therapeutic Vaccine.
[0132] The invention also relates to the use of a polypeptide or
nucleic acid of the invention for use as therapeutic vaccines as
have been described by D. Lowrie (Lowrie, 1999) using DNA vaccine
encoding HSP65 from M. leprae. Antigens with therapeutic properties
may be identified based on their ability to diminish the severity
of M. tuberculosis infection in experimental animals or prevent
reactivation of previous infection, when administered as a vaccine.
The composition used for therapeutic vaccines can be prepared as
described above for vaccines.
Diagnostic Protein
[0133] The invention also relates to a method of diagnosing latent
TB caused by a virulent mycobacterium in an animal, including a
human being, comprising intradermally injecting, in the animal, a
polypeptide according to the invention, a positive skin response at
the location of injection being indicative of the animal having TB,
and a negative skin response at the location of injection being
indicative of the animal not having TB.
[0134] When diagnosis of latent infection with virulent
mycobacteria is the aim, a blood sample comprising mononuclear
cells (i.e. T-lymphocytes) from a patient is contacted with a
sample of one or more polypeptides of the invention. This
contacting can be performed in vitro and a positive reaction could
e.g. be proliferation of the T-cells or release of cytokines such
as IFN-.gamma. into the extracellular phase. It is also conceivable
to contact a serum sample from a subject with a polypeptide of the
invention, the demonstration of a binding between antibodies in the
serum sample and the polypeptide being indicative of previous or
ongoing infection.
[0135] The invention therefore also relates to an in vitro method
for diagnosing latent infection in an animal or a human being with
a virulent mycobacterium, the method comprising providing a blood
sample from the animal or human being, and contacting the sample
from the animal with the polypeptide of the invention, a
significant release into the extracellular phase of at least one
cytokine by mononuclear cells in the blood sample being indicative
of the animal being sensitized. A positive response being a
response more than release from a blood sample derived from a
patient without the TB diagnosis plus two standard deviations. The
invention also relates to the in vitro method for diagnosing
ongoing or previous sensitization in an animal or a human being
with a virulent mycobacterium, the method comprising providing a
blood sample from the animal or human being, and by contacting the
sample from the animal with the polypeptide of the invention
demonstrating the presence of antibodies recognizing the
polypeptide of the invention in the serum sample.
[0136] The immunogenic composition used for diagnosing may comprise
1-20, such as 2-20 or even 3-20 different polypeptides or fusion
polypeptides, such as 3-10 different polypeptides or fusion
polypeptides.
Diagnostic DNA
[0137] The nucleic acid probes encoding the polypeptide of the
invention can be used in a variety of diagnostic assays for
detecting the presence of pathogenic organisms in a given
sample.
[0138] A method of determining the presence of mycobacterial
nucleic acids in an animal, including a human being, or in a
sample, comprising administering a nucleic acid fragment of the
invention to the animal or incubating the sample with the nucleic
acid fragment of the invention or a nucleic acid fragment
complementary thereto, and detecting the presence of hybridized
nucleic acids resulting from the incubation (by using the
hybridization assays which are well-known in the art), is also
included in the invention. Such a method of diagnosing TB might
involve the use of a composition comprising at least a part of a
nucleotide sequence as defined above and detecting the presence of
nucleotide sequences in a sample from the animal or human being to
be tested which hybridize with the nucleic acid fragment (or a
complementary fragment) by the use of PCR technique.
Antibodies
[0139] A monoclonal or polyclonal antibody, which is specifically
reacting with a polypeptide of the invention in an immunoassay, or
a specific binding fragment of said antibody, is also a part of the
invention. The antibodies can be produced by methods known to a
person skilled in the art. Polyclonal antibodies can be raised in a
mammal, for example, by one or more injections of a polypeptide
according to the present invention and, if desired, an adjuvant.
The monoclonal antibodies according to the present invention may,
for example, be produced by the hybridoma method first described by
Kohler and Milstein (Kohler and Milstein, 1975), or may be produced
by recombinant DNA methods such as described in U.S. Pat. No.
4,816,567. The monoclonal antibodies may also be isolated from
phage libraries generated using the techniques described by
McCafferty et al (McCafferty, 1990), for example. Methods for
producing antibodies are described in the literature, e.g. in U.S.
Pat. No. 6,136,958.
[0140] A sample of a potentially infected organ or body fluid from
an infected individual may be contacted with such an antibody
recognizing a polypeptide of the invention. The demonstration of
the reaction by means of methods well known in the art between the
sample and the antibody will be indicative of an ongoing infection.
It is of course also a possibility to demonstrate the presence of
anti-mycobacterial antibodies in serum or other body fluids by
contacting a serum sample from a subject with at least one of the
polypeptide fragments of the invention and using well-known methods
for visualizing the reaction between the antibody and antigen.
[0141] In diagnostics, an antibody, a nucleic acid fragment and/or
a polypeptide of the invention can be used either alone, or as a
constituent in a composition. Such compositions are known in the
art, and comprise compositions in which the antibody, the nucleic
acid fragment or the polypeptide of the invention is coupled,
preferably covalently, to at least one other molecule, e.g. a label
(e.g. radioactive or fluorescent) or a carrier molecule.
[0142] It will be understood that the following examples are
illustrative of the present invention and are not a limitation
thereof. A number of variations on the techniques, reagents, and
conditions described in the following examples will be readily
apparent to one of skill in the art.
EXAMPLES
Example 1
Cloning and Expression of Low Oxygen Induced M. Tuberculosis
Antigens in E. coli
[0143] A number of M. tuberculosis genes are induced under low
oxygen conditions. The up-regulation of the genes listed in table 2
has been determined at either the mRNA (Sherman, 2001) or protein
(Boon, 2001, Rosenkrands, 2002) level. The coding region of these
selected antigens is amplified by PCR using the primer sets listed
in Table 3.
TABLE-US-00004 TABLE 3 Primer sequences for PCR amplification of
selected low oxygen induced antigens SEQ Rv no. ID NO: Primer
sequence Rv0079 Fwd 92 CACCGTGGAACCGAAACGCAGTCG Rvs 93
TTATGCCAGACCGTCGGCA Rv0080 Fwd 94 CACCATGAGCCCGGGCTCG Rvs 95
TTACGGCGTACGCGAGTCAG Rv0081 Fwd 96 CACCGTGGAGTCCGAACCGCTGTA Rvs 97
TTACGTGGCCGAGCCGC Rv0363c Fwd 98 CACCATGCCTATCGCAACGCCC (fba) Rvs
99 TTAGTGGGTTAGGGACTTTCCGG Rv0569 Fwd 100
GGGGACAAGTTTGTACAAAAAAGCAGGCTTAAAGGCAAAGGTCGGGGAC Rvs 101
GGGGACCACTTTGTACAAGAAAGCTGGGTCCTACGTTCCCCTGGCATGGA Rv0572c Fwd 102
CACCATGGGTGAGCACGCCATC Rvs 103 TTATAGGTCATCGGATTGAGGTGATC Rv0574c
Fwd 104 CACCGTGGCTGGCAATCCTGATGT Rvs 105 TTACTCCTTGCTCGTTAGGTTGGC
Rv1264 Fwd 106 CACCGTGACAGACCACGTGCGC Rvs 107 TTACGGTGACGAGCCGGC
Rv1592c Fwd 108 CACCATGGTAGAGCCCGGCAATTTG Rvs 109
TTAGAGCGGACGGCGGCT Rv1733c Fwd 110 CACCATGATCGCCACAACCCGC Rvs 111
TTACCGCTGCGTGCAGAACA Rv1734c Fwd 112 CACCATGACCAACGTCGGTGACCA Rvs
113 TTATCCTGTTACTGCGGCGCA Rv1736c Fwd 114 CACCGTGACGGTGACACCACGGAC
(narX) Rvs 115 TTACCACCCGCGCCGC Rv1737c Fwd 116
CACCATGAGAGGGCAAGCGGC (narK2) Rvs 117 TTACCTGGACGCCTCCTCACTC Rv1738
Fwd 118 CACCATGTGCGGCGACCAGTC Rvs 119 TTAATACAACAATCGCGCCGG Rv1739c
Fwd 120 CACCATGATTCCCACGATGACATCG Rvs 121 TTAGCGCCGACGGAACG Rv1813c
Fwd 122 GGGGACAAGTTTGTACAAAAAAGCAGGCTTAATCACAAACCTCCGACGC Rvs 123
GGGGACCACTTTGTACAAGAAAGCTGGGTCCTAGTTGCACGCCCAGTTGA C Rv1997 Fwd 124
CACCTTGTCGGCGTCAGTGTCTGC (ctpF) Rvs 125 TTATGGCGGTTGCGCCC Rv1998c
Fwd 126 CACCATGAGTTTCCACGATCTTCATCACC Rvs 127
TTACGTTGTACTCGTGCGGTTCTC Rv2003c Fwd 128 CACCGTGGTCAAGCGCTCTCGG Rvs
129 TTATTCCGACTCGAGTGGGTGA Rv2005c Fwd 130 CACCATGTCTAAACCCCGCAAGCA
Rvs 131 TTACGACTGCCGTGCCACG Rv2007c Fwd 132
CACCGTGACCTATGTGATCGGTAGTGAGTG (fdxA) Rvs 133 TTAAGGGCACTCCACCGGGA
Rv2028c Fwd 134 CACCATGAACCAATCACACAAACCCC Rvs 135
TTACAGATACTGCTGACCGACGACC Rv2029c Fwd 136 CACCATGACGGAGCCAGCGG
(PfkB) Rvs 137 TTATGGCGAGGCTTCCGG Rv2030c Fwd 138
GGGGACAAGTTTGTACAAAAAAGCAGGCTTACTGATGACCGCAGCGGCT Rvs 139
GGGGACCACTTTGTACAAGAAAGCTGGGTCCTACAGACCGGTCGGGTAGG TTT Rv2031c Fwd
140 GGGGACAAGTTTGTACAAAAAAGCAGGCTTAGCCACCACCCTTCCCGT (hspX) Rvs 141
GGGGACCACTTTGTACAAGAAAGCTGGGTCCTAGTTGGTGGACCGGATCT GAAT Rv2032 Fwd
142 CACCATGCCGGACACCATGGTG Rvs 143 TTAGTGATCCTTAGCCCGAACGTG Rv2428
Fwd 144 GGGGACAAGTTTGTACAAAAAAGCAGGCTTAATGCCACTGCTAACCATTG GC
(ahpC) Rvs 145 GGGGACCACTTTGTACAAGAAAGCTGGGTCCTAGGCCGAAGCCTTGAGGA
GT Rv2624c Fwd 146 CACCATGTCTGGGAGAGGAGAGCCG Rvs 147
TTAGCGAACGACAAGCACCGA Rv2625c Fwd 148
GGGGACAAGTTTGTACAAAAAAGCAGGCTTACGTGATGCGATCCCGCT Rvs 149
GGGGACCACTTTGTACAAGAAAGCTGGGTCCTACCCCGCATCGGAAAACC Rv2627c Fwd 150
GGGGACAAGTTTGTACAAAAAAGCAGGCTTAATGGCAAGTTCTGCGAGCG A Rvs 151
GGGGACCACTTTGTACAAGAAAGCTGGGTCCTAGGAACGGTCGCGCTGTG T Rv2628 Fwd 152
CACCATGTCCACGCAACGACCG Rvs 153 TTAACCGCAACGGCAATCTCA Rv2629 Fwd 154
CACCATGCGATCAGAACGTCTCCG Rvs 155 TTAGGATCTATGGCTGCCGAGTC Rv2630 Fwd
156 CACCATGCTGCACCGCGACGA Rvs 157 TTACACATCGAGCGTTACCGCAC Rv2659c
Fwd 158 GGGGACAAGTTTGTACAAAAAAGCAGGCTTAGTGACGCAAACCGGCAA Rvs 159
GGGGACCACTTTGTACAAGAAAGCTGGGTCCTACATCTCCTGGTTCTCGG CC Rv2780 Fwd
160 GGGGACAAGTTTGTACAAAAAAGCAGGCTTACGCGTCGGTATTCCGACC Rvs 161
GGGGACCACTTTGTACAAGAAAGCTGGGTCCTACACGCTGGCGGGCTC Rv3126c Fwd 162
CACCATGGTCATCCGGTTTGATCAAATA Rvs 163 TTATGGATTGTCAATGACAGCCCA
Rv3127 Fwd 164 CACCGTGCTCAAGAACGCAGTCTTGC Rvs 165
TTAAGGCGGGCTGAACCAACC Rv3128c Fwd 166 CACCGTGTGGTCCGCCTCGG Rvs 167
TTAGCCCGCCTTGATCAGGA Rv3129 Fwd 168 CACCGTGGTGCAAGGCCGCA Rvs 169
TTATCGCTGGTTGTGTGACGAG Rv3130c Fwd 170
CACCATGAATCACCTAACGACACTTGACG Rvs 171 TTACACAACCAGCGATAGCGCTC
Rv3131 Fwd 172 CACCATGAACACCCATTTCCCGG Rvs 173
TTAGCACCGTTGTCGCAGTAGCT Rv3132c Fwd 174 CACCATGACAACAGGGGGCCTCG Rvs
175 TTACTGCGACAACGGTGCTGAC Rv3134c Fwd 176 CACCATGAGCGATCCTCGGCCA
Rvs 177 TTACAAGTTGGCACTGCGTACCG Rv3841 Fwd 178
CCGGCTGAGATCTATGACAGAATACGAAGGGC (bfrB) Rvs 179
CCCCGCCAGGGAACTAGAGGCGGC Rv3842c Fwd 180 CACCATGACATGGGCCGACGAG
(glpQ1) Rvs 181 TTAGCGAGTGGTCCCGTTCG Rv3908 Fwd 182
CACCGTGTCCGACGGCGAACAA Rvs 183 TTACGGCCCCGGCCC
[0144] PCR reactions were carried out using Platinum Tag DNA
Polymerase (GIBCO BRL) in a 50 .mu.l reaction volume containing 60
mM Tris-SO.sub.4 (pH 8.9), 18 mM Ammonium Sulfate, 0.2 mM of each
of the four nucleotides, 0.2 .mu.M of each primer and 10 ng of M.
tuberculosis H37Rv chromosomal DNA. The reaction mixtures were
initially heated to 95.degree. C. for 5 min., followed by 35 cycles
of: 95.degree. C. for 45 sec, 60.degree. C. for 45 sec and
72.degree. C. for 2 min. The amplification products were
precipitated by PEG/MgCl.sub.2, and dissolved in 50 .mu.L TE
buffer.
[0145] DNA fragments were cloned and expressed in Gateway Cloning
system (Life Technology). First, to create Entry Clones, 5 .mu.L of
DNA fragment was mixed with 1 .mu.L of pDONR201, 2 .mu.L of BP
CLONASE enzyme mix and 2 .mu.L of BP reaction buffer. The
recombination reactions were carried out at 25.degree. C. for 60
min. After Proteinase K treatment at 37.degree. C. for 10 min., 5
.mu.L of each sample was used to transform E. coli DH5.alpha.
competent cells. Transformants were selected on LB plates
containing 50 .mu.g/mL kanamycin. One bacterial clone from each
transformation was grown in 3 mL LB medium containing 50 .mu.g/mL
kanamycin and plasmid DNA was isolated (Qiagen).
[0146] Second, to create expression clones, 2 .mu.L of each entry
clone DNA was mixed with .mu.L of His-tagged expression vector
(pDest17), 2 .mu.L LR reaction buffer, 2 .mu.L LR CLONASE enzyme
mix and 3 .mu.L TE. After recombination at 25.degree. C. for 60
min. and Proteinase K treatment at 37.degree. C. for 10 min., 5
.mu.L of each sample was used to transform E. coli BL21-SI
competent cells. Transformants were selected on LBON (LB without
NaCl) plates containing 100 .mu.g/mL ampicillin. The resulting E.
coli clones express recombinant proteins carrying a 6-histine tag
at the N-terminal. All clones were confirmed by DNA sequencing.
[0147] Recombinant proteins were purified from transformed E. coli
BL21-SI cells cultured in 900 mL LBON medium containing 100
.mu.g/mL at 30.degree. C. until OD.sub.600=0.4-0.6. At this point
100 mL 3 M NaCl was added and 3 hours later bacteria were harvested
by centrifugation. Bacteria pellets were resuspended in 20 mL
bacterial protein extraction reagent (Pierce) incubated for 10 min.
at room temperature and pelleted by centrifugation. Bacteria were
lysed and their DNA digested by treating with lysozyme (0.1 mg/mL)
and DNase I (2.5 .mu.g/mL) at room temperature for 30 minutes, with
gentle agitation. The recombinant protein forms inclusion bodies
and can be pelleted by centrifugation at 27.000.times.g for 15 min.
Protein pellets were solubilized by adding 20 ml of sonication
buffer (8 M urea, 50 mM Na.sub.2HPO.sub.4, 100 mM Tris-HCl, pH 8.0)
and sonicating 5.times.30 sec pulses interrupted by a 30 sec pause.
After another centrifugation at 27.000.times.g for 15 min.,
supernatants were applied to 10 mL TALON columns (Clontech). The
columns were washed with 50 mL sonication buffer. Bound proteins
were eluted by lowering pH (8 M urea, 50 mM Na.sub.2HPO.sub.4, 100
mM Tris-HCl, pH 4.5). 5 mL fractions were collected and analyzed by
SDS-PAGE. Fractions containing recombinant protein were pooled.
Further purification was achieved by anion- or cation-exchange
chromatography on Hitrap columns (Pharmacia). Bound protein was
eluted using a NaCl gradient from 0-500 mM in 3 M urea, 10 mM
Tris-HCl, pH 8.0. All fractions were collected and analyzed on
SDS-PAGE using Coomassie staining. Fractions containing recombinant
protein were pooled. Final protein concentrations were determined
by micro BCA (Pierce).
Example 2
Prophylactic Versus Therapeutic Vaccine
Murine Vaccination Models.
[0148] A prophylactic vaccine given prior to infection should
induce an immune response sufficiently strong to prevent or dampen
the initial proliferation of the bacteria in the acute phase and
thereby reduce the ensuing disease. In the murine prophylactic
vaccine model outlined in FIG. 1A, nai{umlaut over (v)}e mice are
immunized 3 times, 2 weeks apart with recombinant antigens. Six
weeks after the last immunization, the mice are given an aerosol
infection with approximately 250 M. tuberculosis bacilli. The
protective capacity of the vaccine is evaluated by enumeration of
the bacteria in spleen and lung 6 weeks post-infection.
[0149] To define the optimal components for a therapeutic vaccine,
a murine reactivation model of latent TB has been established (van
Pinxteren, 2000) (FIG. 1B). An aerosol infection with approximately
250 M. tuberculosis bacilli is given and at the peak of infection 6
weeks later, the mice receive an 8-week course of
anti-mycobacterial drug treatment of isoniazid and rifabutin given
in the drinking water. This reduces the bacterial load in spleen
and lung to a low level (about 500 bacteria per organ). This latent
phase of low chronic infection is stable for 9-10 weeks after which
a slow spontaneous reactivation occurs. The therapeutic vaccine is
given as 3 subcutaneous (s.c.) immunizations about 5 weeks after
cessation of drug treatment. The effect of the therapeutic vaccine
is evaluated as protection against reactivation determined by
enumeration of bacteria in spleen and lung 7 weeks after the last
immunization.
[0150] The effect of the antigens in a prophylactic or a
therapeutic vaccine.
[0151] BCG, ESAT6, and Rv2031c, one of the most prominent proteins
induced under low oxygen conditions (Rosenkrands, 2002), were
analyzed for their prophylactic and therapeutic vaccine potential.
Naive or latently infected C57Bl mice were immunized with one s.c.
injection of 2.5.times.10.sup.5 BCG, or 3 s.c. immunizations of 10
.mu.g of either recombinant ESAT6 or recombinant Rv2031c in a
DDA/MPL adjuvant. The vaccinations were done in groups of 5 mice
and protective capacity of the vaccines was evaluated as described
above. FIG. 2 shows the bacterial load in the lung in the acute
phase (A) and in the reactivation phase (B), after prophylactic and
therapeutic vaccination respectively. ESAT6 (as previously
described by Brandt, 2000) offers protection against acute phase
infection at the level of BCG (FIG. 2A). However, neither of the
two shows any protective effect against reactivation of the
infection when given during latent infection (FIG. 2B). In
contrast, Rv2031c, the low oxygen induced antigen, offers no
protection against the acute phase of the infection when given as a
prophylactic vaccine, but gives some protection against
reactivation when given as a therapeutic vaccine. That is, some
antigens, here exemplified by ESAT6, though potent as prophylactic
vaccines have no effect as therapeutic vaccines. In contrast, other
antigens, here exemplified by Rv2031c, can be efficient therapeutic
vaccines although they have no effect or only negligible effect as
prophylactic vaccines.
Example 3
Low Oxygen Induced Antigens, Rv2031c, as Therapeutic Vaccines
[0152] There is a high variability in bacterial load intrinsic to
the reactivation model in the latent and reactivation phase. The
analysis of Rv2031c as a therapeutic vaccine was therefore repeated
in groups of eight mice. As in the previous experiments the mice
were given 3 s.c. immunizations of 10 .mu.g rRv2031c in DDA/MPL.
The induced immune responses were analyzed one week post
immunization. The mice were partially bled and the PBMC from the
blood purified and analyzed for Rv2031c- and ESAT6 specific recall
responses. Using ELIspot technique, the frequency of
Rv2031c-specific and ESAT6-specific IFN-.gamma.-producing cells
were determined in both the rRv2031c immunized and the unimmunized
group (FIG. 3). The rRv2031c immunization has increased the
frequency of Rv2031c-specific IFN-.gamma. producing cells by a
factor of 43 as compared to the unimmunized group. In contrast, the
frequency of ESAT6-specific IFN-.gamma. producing cells is
significantly higher in the unimmunized group. ESAT6 is an antigen
produced in high amounts by the actively-growing M. tuberculosis
bacteria. The level of the ESAT6 specific immune response in
infected mice could therefore be indicative the degree of
actively-growing infection in the animals. Recent reports have in
fact demonstrated such a correlation between the level of ESAT6
response and degree of disease in both M. tuberculosis-infected
humans and M. bovis-infected cattle (Doherty, 2002, Vordermeier,
2002). Therefore, the higher ESAT6 response in the unimmunized
group of latently-infected mice could be indicative of a transition
into the reactivation phase, where the bacteria are again beginning
to multiply.
[0153] To analyze the epitope recognition pattern of Rv2031c,
fourteen overlapping peptides (each 20 amino acids long) covering
the whole Rv2031c protein were synthesized. Initially the peptides
were analyzed in 4 pools of 3-4 peptides. PBMCs from rRv2031c
immunized latently-infected mice were incubated with the peptide
pools (5 .mu.g/ml per peptide) for 72 h. The specific
peptide-induced IFN-.gamma. production was quantitated in the
supernatant in a standard sandwich ELISA using paired anti-murine
IFN-.gamma. antibodies (PharMingen) and recombinant IFN-.gamma.
(PharMingen) as standard. Both peptide pool 1-4 and 8-10 stimulated
a significant IFN-.gamma. response (FIG. 4A). The individual
peptides of these two pools were re-analyzed (FIG. 4B). This
clearly shows that the response to Rv2031c contains a dominant
epitope, peptide 2 (PRSLFPEFSELFAAFPSFAG, aa 11-30 of SEQ ID
NO:24), and a subdominant epitope, peptide 9 (RTEQKDFDGRSEFAYGSFVR,
aa 81-100 of SEQ ID NO:24).
[0154] The therapeutic effect of the rRv2031c immunizations was
analyzed 7 weeks after the last immunization. FIG. 5 shows the
bacterial load in the lung (A) and the spleen (B) of both
rRv2031c-immunized and unimmunized mice. There is a clear reduction
in the level of bacteria in both organs in the rRv2031c-immunized
group. That is, the induction of Rv2031c T cell responses can
participate in keeping the latent infection in check.
Example 4
Low Oxygen Induced Antigens, Rv0569, as Therapeutic Vaccines
[0155] Rv0569 is also a low oxygen induced antigen described in
WO0179274 and illustrates very well the potential as a therapeutic
vaccine.
[0156] We have established a murine reactivation model of latent TB
[van Pinxteren et al, 2000, 30:3689-98], which is a variant of the
so-called Cornell model. An aerosol infection is allowed to be
established and at the peak of infection 6 weeks after, the mice
receive an 8-week course of anti-mycobacterial drug treatment of
isoniazid and rifabutin given in the drinking water. This reduces
the bacterial load in spleen and lung to a low level. This latent
phase of low chronic infection is stable for 9-10 weeks after which
a slow spontaneous reactivation can be detected. This model is used
to analyze the protective effect of a post exposure vaccine on
reactivation.
[0157] Rv0569, which is highly up regulated under low oxygen growth
conditions [Rosenkrands et al, 2002, 184(13): 3485-91], was
analyzed for its ability to protect against reactivation given as a
therapeutic vaccine in the latent phase of TB infection. Latent
infected C57Bl mice were vaccinated with 3 s.c. injections of 3
.mu.g recombinant Rv0569 and for comparison with 3 s.c. injections
of 3 .mu.g recombinant ESAT6 or one s.c. injection of BCG. The
effect of the vaccine is evaluated 7 weeks after the last
immunization. The induced immune responses were analyzed for Rv0569
or ESAT6 specific responses in an in vitro recall assay. Isolated
splenocytes were incubated with 1 .mu.g/ml of Rv0569 or 1 .mu.g/ml
of ESAT6 for 72 h. The produced IFN.gamma. in the culture
supernatant was quantitated in a standard sandwich ELISA. FIG. 6
shows a nice Rv0569 specific IFN.gamma. response induced in the
Rv0569 vaccinated group with practically no response in the
un-vaccinated group. The ESAT6 vaccination enhanced the ESAT6
specific response though a significant ESAT6 response persisted in
the un-vaccinated latent infected group.
[0158] The Rv0569 induced protection against reactivation was
determined by enumeration of bacteria in spleen and lung 7 weeks
after the last immunization. FIG. 7 shows the bacterial load in the
lung and the spleen of both Rv0569-vaccinated, ESAT6-vaccinated,
BCG vaccinated and un-vaccinated latently infected mice. There is a
clear reduction in the level of viable bacteria in both spleen and
lungs of the Rv0569 vaccinated mice, whereas neither ESAT6 nor BCG
are able to inhibit the growth of the M. tuberculosis bacteria when
given as a vaccine during latent infection. That is, the induction
of Rv0569 T cell responses can participate in keeping the latent
infection in check.
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[0178] Olsen A. W et al, Eur J. Immunol. 2000 June; 30(6):1724-32
[0179] Danish Patent application PA 2000 00666 "Nucleic acid
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[0180] Danish Patent application PA 1999 01020 (WO 01/23388)
"Tuberculosis vaccine and diagnostic based on the Mycobacterium
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al. 1988. Proc Natl Acad Sci USA, 85, 2444-2448. [0183] Ravn, P. et
al 1999. J. Infect. Dis. 179:637-645 [0184] Rolph, M. S, and I. A.
Ramshaw. 1997. Curr. Opin. Immunol. 9:517-24 [0185] Rosenkrands,
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Sambrook et al Molecular Cloning; A laboratory manual, Cold Spring
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[0196] All documents listed above, and the sequence listing, are
incorporated by reference herein. A variety of modifications and
variations on the processes, conditions, reagents and compositions
described herein will be readily apparent to one of skill in the
art given the teachings of the present invention. Such
modifications and variations are within the scope of the invention
as set forth in the following claims.
Sequence CWU 1
1
1871273PRTMycobacterium tuberculosis 1Val Glu Pro Lys Arg Ser Arg
Leu Val Val Cys Ala Pro Glu Pro Ser1 5 10 15His Ala Arg Glu Phe Pro
Asp Val Ala Val Phe Ser Gly Gly Arg Ala 20 25 30Asn Ala Ser Gln Ala
Glu Arg Leu Ala Arg Ala Val Gly Arg Val Leu 35 40 45Ala Asp Arg Gly
Val Thr Gly Gly Ala Arg Val Arg Leu Thr Met Ala 50 55 60Asn Cys Ala
Asp Gly Pro Thr Leu Val Gln Ile Asn Leu Gln Val Gly65 70 75 80Asp
Thr Pro Leu Arg Ala Gln Ala Ala Thr Ala Gly Ile Asp Asp Leu 85 90
95Arg Pro Ala Leu Ile Arg Leu Asp Arg Gln Ile Val Arg Ala Ser Ala
100 105 110Gln Trp Cys Pro Arg Pro Trp Pro Asp Arg Pro Arg Arg Arg
Leu Thr 115 120 125Thr Pro Ala Glu Ala Leu Val Thr Arg Arg Lys Pro
Val Val Leu Arg 130 135 140Arg Ala Thr Pro Leu Gln Ala Ile Ala Ala
Met Asp Ala Met Asp Tyr145 150 155 160Asp Val His Leu Phe Thr Asp
Ala Glu Thr Gly Glu Asp Ala Val Val 165 170 175Tyr Arg Ala Gly Pro
Ser Gly Leu Arg Leu Ala Arg Gln His His Val 180 185 190Phe Pro Pro
Gly Trp Ser Arg Cys Arg Ala Pro Ala Gly Pro Pro Val 195 200 205Pro
Leu Ile Val Asn Ser Arg Pro Thr Pro Val Leu Thr Glu Ala Ala 210 215
220Ala Val Asp Arg Ala Arg Glu His Gly Leu Pro Phe Leu Phe Phe
Thr225 230 235 240Asp Gln Ala Thr Gly Arg Gly Gln Leu Leu Tyr Ser
Arg Tyr Asp Gly 245 250 255Asn Leu Gly Leu Ile Thr Pro Thr Gly Asp
Gly Val Ala Asp Gly Leu 260 265 270Ala2152PRTMycobacterium
tuberculosis 2Met Ser Pro Gly Ser Arg Arg Ala Ser Pro Gln Ser Ala
Arg Glu Val1 5 10 15Val Glu Leu Asp Arg Asp Glu Ala Met Arg Leu Leu
Ala Ser Val Asp 20 25 30His Gly Arg Val Val Phe Thr Arg Ala Ala Leu
Pro Ala Ile Arg Pro 35 40 45Val Asn His Leu Val Val Asp Gly Arg Val
Ile Gly Arg Thr Arg Leu 50 55 60Thr Ala Lys Val Ser Val Ala Val Arg
Ser Ser Ala Asp Ala Gly Val65 70 75 80Val Val Ala Tyr Glu Ala Asp
Asp Leu Asp Pro Arg Arg Arg Thr Gly 85 90 95Trp Ser Val Val Val Thr
Gly Leu Ala Thr Glu Val Ser Asp Pro Glu 100 105 110Gln Val Ala Arg
Tyr Gln Arg Leu Leu His Pro Trp Val Asn Met Ala 115 120 125Met Asp
Thr Val Val Ala Ile Glu Pro Glu Ile Val Thr Gly Ile Arg 130 135
140Ile Val Ala Asp Ser Arg Thr Pro145 1503114PRTMycobacterium
tuberculosis 3Val Glu Ser Glu Pro Leu Tyr Lys Leu Lys Ala Glu Phe
Phe Lys Thr1 5 10 15Leu Ala His Pro Ala Arg Ile Arg Ile Leu Glu Leu
Leu Val Glu Arg 20 25 30Asp Arg Ser Val Gly Glu Leu Leu Ser Ser Asp
Val Gly Leu Glu Ser 35 40 45Ser Asn Leu Ser Gln Gln Leu Gly Val Leu
Arg Arg Ala Gly Val Val 50 55 60Ala Ala Arg Arg Asp Gly Asn Ala Met
Ile Tyr Ser Ile Ala Ala Pro65 70 75 80Asp Ile Ala Glu Leu Leu Ala
Val Ala Arg Lys Val Leu Ala Arg Val 85 90 95Leu Ser Asp Arg Val Ala
Val Leu Glu Asp Leu Arg Ala Gly Gly Ser 100 105 110Ala
Thr4344PRTMycobacterium tuberculosis 4Met Pro Ile Ala Thr Pro Glu
Val Tyr Ala Glu Met Leu Gly Gln Ala1 5 10 15Lys Gln Asn Ser Tyr Ala
Phe Pro Ala Ile Asn Cys Thr Ser Ser Glu 20 25 30Thr Val Asn Ala Ala
Ile Lys Gly Phe Ala Asp Ala Gly Ser Asp Gly 35 40 45Ile Ile Gln Phe
Ser Thr Gly Gly Ala Glu Phe Gly Ser Gly Leu Gly 50 55 60Val Lys Asp
Met Val Thr Gly Ala Val Ala Leu Ala Glu Phe Thr His65 70 75 80Val
Ile Ala Ala Lys Tyr Pro Val Asn Val Ala Leu His Thr Asp His 85 90
95Cys Pro Lys Asp Lys Leu Asp Ser Tyr Val Arg Pro Leu Leu Ala Ile
100 105 110Ser Ala Gln Arg Val Ser Lys Gly Gly Asn Pro Leu Phe Gln
Ser His 115 120 125Met Trp Asp Gly Ser Ala Val Pro Ile Asp Glu Asn
Leu Ala Ile Ala 130 135 140Gln Glu Leu Leu Lys Ala Ala Ala Ala Ala
Lys Ile Ile Leu Glu Ile145 150 155 160Glu Ile Gly Val Val Gly Gly
Glu Glu Asp Gly Val Ala Asn Glu Ile 165 170 175Asn Glu Lys Leu Tyr
Thr Ser Pro Glu Asp Phe Glu Lys Thr Ile Glu 180 185 190Ala Leu Gly
Ala Gly Glu His Gly Lys Tyr Leu Leu Ala Ala Thr Phe 195 200 205Gly
Asn Val His Gly Val Tyr Lys Pro Gly Asn Val Lys Leu Arg Pro 210 215
220Asp Ile Leu Ala Gln Gly Gln Gln Val Ala Ala Ala Lys Leu Gly
Leu225 230 235 240Pro Ala Asp Ala Lys Pro Phe Asp Phe Val Phe His
Gly Gly Ser Gly 245 250 255Ser Leu Lys Ser Glu Ile Glu Glu Ala Leu
Arg Tyr Gly Val Val Lys 260 265 270Met Asn Val Asp Thr Asp Thr Gln
Tyr Ala Phe Thr Arg Pro Ile Ala 275 280 285Gly His Met Phe Thr Asn
Tyr Asp Gly Val Leu Lys Val Asp Gly Glu 290 295 300Val Gly Val Lys
Lys Val Tyr Asp Pro Arg Ser Tyr Leu Lys Lys Ala305 310 315 320Glu
Ala Ser Met Ser Gln Arg Val Val Gln Ala Cys Asn Asp Leu His 325 330
335Cys Ala Gly Lys Ser Leu Thr His 3405113PRTMycobacterium
tuberculosis 5Met Gly Glu His Ala Ile Lys Arg His Met Arg Gln Arg
Lys Pro Thr1 5 10 15Lys His Pro Leu Ala Gln Lys Arg Gly Ala Arg Ile
Leu Val Phe Thr 20 25 30Asp Asp Pro Arg Arg Ser Val Leu Ile Val Pro
Gly Cys His Leu Asp 35 40 45Ser Met Arg Arg Glu Lys Asn Ala Tyr Tyr
Phe Gln Asp Gly Asn Ala 50 55 60Leu Val Gly Met Val Val Ser Gly Gly
Thr Val Glu Tyr Asp Ala Asp65 70 75 80Asp Arg Thr Tyr Val Val Gln
Leu Thr Asp Gly Arg His Thr Thr Glu 85 90 95Ser Ser Phe Glu His Ser
Ser Pro Ser Arg Ser Pro Gln Ser Asp Asp 100 105
110Leu6380PRTMycobacterium tuberculosis 6Val Ala Gly Asn Pro Asp
Val Val Thr Val Leu Leu Gly Gly Asp Val1 5 10 15Met Leu Gly Arg Gly
Val Asp Gln Ile Leu Pro His Pro Gly Lys Pro 20 25 30Gln Leu Arg Glu
Arg Tyr Met Arg Asp Ala Thr Gly Tyr Val Arg Leu 35 40 45Ala Glu Arg
Val Asn Gly Arg Ile Pro Leu Pro Val Asp Trp Arg Trp 50 55 60Pro Trp
Gly Glu Ala Leu Ala Val Leu Glu Asn Thr Ala Thr Asp Val65 70 75
80Cys Leu Ile Asn Leu Glu Thr Thr Ile Thr Ala Asp Gly Glu Phe Ala
85 90 95Asp Arg Lys Pro Val Cys Tyr Arg Met His Pro Asp Asn Val Pro
Ala 100 105 110Leu Thr Ala Leu Arg Pro His Val Cys Ala Leu Ala Asn
Asn His Ile 115 120 125Leu Asp Phe Gly Tyr Gln Gly Leu Thr Asp Thr
Val Ala Ala Leu Ala 130 135 140Gly Ala Gly Ile Gln Ser Val Gly Ala
Gly Ala Asp Leu Leu Ala Ala145 150 155 160Arg Arg Ser Ala Leu Val
Thr Val Gly His Glu Arg Arg Val Ile Val 165 170 175Gly Ser Val Ala
Ala Glu Ser Ser Gly Val Pro Glu Ser Trp Ala Ala 180 185 190Arg Arg
Asp Arg Pro Gly Val Trp Leu Ile Arg Asp Pro Ala Gln Arg 195 200
205Asp Val Ala Asp Asp Val Ala Ala Gln Val Leu Ala Asp Lys Arg Pro
210 215 220Gly Asp Ile Ala Ile Val Ser Met His Trp Gly Ser Asn Trp
Gly Tyr225 230 235 240Ala Thr Ala Pro Gly Asp Val Ala Phe Ala His
Arg Leu Ile Asp Ala 245 250 255Gly Ile Asp Met Val His Gly His Ser
Ser His His Pro Arg Pro Ile 260 265 270Glu Ile Tyr Arg Gly Lys Pro
Ile Leu Tyr Gly Cys Gly Asp Val Val 275 280 285Asp Asp Tyr Glu Gly
Ile Gly Gly His Glu Ser Phe Arg Ser Glu Leu 290 295 300Arg Leu Leu
Tyr Leu Thr Val Thr Asp Pro Ala Ser Gly Asn Leu Ile305 310 315
320Ser Leu Gln Met Leu Pro Leu Arg Val Ser Arg Met Arg Leu Gln Arg
325 330 335Ala Ser Gln Thr Asp Thr Glu Trp Leu Arg Asn Thr Ile Glu
Arg Ile 340 345 350Ser Arg Arg Phe Gly Ile Arg Val Val Thr Arg Pro
Asp Asn Leu Leu 355 360 365Glu Val Val Pro Ala Ala Asn Leu Thr Ser
Lys Glu 370 375 3807397PRTMycobacterium tuberculosis 7Val Thr Asp
His Val Arg Glu Ala Asp Asp Ala Asn Ile Asp Asp Leu1 5 10 15Leu Gly
Asp Leu Gly Gly Thr Ala Arg Ala Glu Arg Ala Lys Leu Val 20 25 30Glu
Trp Leu Leu Glu Gln Gly Ile Thr Pro Asp Glu Ile Arg Ala Thr 35 40
45Asn Pro Pro Leu Leu Leu Ala Thr Arg His Leu Val Gly Asp Asp Gly
50 55 60Thr Tyr Val Ser Ala Arg Glu Ile Ser Glu Asn Tyr Gly Val Asp
Leu65 70 75 80Glu Leu Leu Gln Arg Val Gln Arg Ala Val Gly Leu Ala
Arg Val Asp 85 90 95Asp Pro Asp Ala Val Val His Met Arg Ala Asp Gly
Glu Ala Ala Ala 100 105 110Arg Ala Gln Arg Phe Val Glu Leu Gly Leu
Asn Pro Asp Gln Val Val 115 120 125Leu Val Val Arg Val Leu Ala Glu
Gly Leu Ser His Ala Ala Glu Ala 130 135 140Met Arg Tyr Thr Ala Leu
Glu Ala Ile Met Arg Pro Gly Ala Thr Glu145 150 155 160Leu Asp Ile
Ala Lys Gly Ser Gln Ala Leu Val Ser Gln Ile Val Pro 165 170 175Leu
Leu Gly Pro Met Ile Gln Asp Met Leu Phe Met Gln Leu Arg His 180 185
190Met Met Glu Thr Glu Ala Val Asn Ala Gly Glu Arg Ala Ala Gly Lys
195 200 205Pro Leu Pro Gly Ala Arg Gln Val Thr Val Ala Phe Ala Asp
Leu Val 210 215 220Gly Phe Thr Gln Leu Gly Glu Val Val Ser Ala Glu
Glu Leu Gly His225 230 235 240Leu Ala Gly Arg Leu Ala Gly Leu Ala
Arg Asp Leu Thr Ala Pro Pro 245 250 255Val Trp Phe Ile Lys Thr Ile
Gly Asp Ala Val Met Leu Val Cys Pro 260 265 270Asp Pro Ala Pro Leu
Leu Asp Thr Val Leu Lys Leu Val Glu Val Val 275 280 285Asp Thr Asp
Asn Asn Phe Pro Arg Leu Arg Ala Gly Val Ala Ser Gly 290 295 300Met
Ala Val Ser Arg Ala Gly Asp Trp Phe Gly Ser Pro Val Asn Val305 310
315 320Ala Ser Arg Val Thr Gly Val Ala Arg Pro Gly Ala Val Leu Val
Ala 325 330 335Asp Ser Val Arg Glu Ala Leu Gly Asp Ala Pro Glu Ala
Asp Gly Phe 340 345 350Gln Trp Ser Phe Ala Gly Pro Arg Arg Leu Arg
Gly Ile Arg Gly Asp 355 360 365Val Arg Leu Phe Arg Val Arg Arg Gly
Ala Thr Arg Thr Gly Ser Gly 370 375 380Gly Ala Ala Gln Asp Asp Asp
Leu Ala Gly Ser Ser Pro385 390 3958446PRTMycobacterium tuberculosis
8Met Val Glu Pro Gly Asn Leu Ala Gly Ala Thr Gly Ala Glu Trp Ile1 5
10 15Gly Arg Pro Pro His Glu Glu Leu Gln Arg Lys Val Arg Pro Leu
Leu 20 25 30Pro Ser Asp Asp Pro Phe Tyr Phe Pro Pro Ala Gly Tyr Gln
His Ala 35 40 45Val Pro Gly Thr Val Leu Arg Ser Arg Asp Val Glu Leu
Ala Phe Met 50 55 60Gly Leu Ile Pro Gln Pro Val Thr Ala Thr Gln Leu
Leu Tyr Arg Thr65 70 75 80Thr Asn Met Tyr Gly Asn Pro Glu Ala Thr
Val Thr Thr Val Ile Val 85 90 95Pro Ala Glu Leu Ala Pro Gly Gln Thr
Cys Pro Leu Leu Ser Tyr Gln 100 105 110Cys Ala Ile Asp Ala Met Ser
Ser Arg Cys Phe Pro Ser Tyr Ala Leu 115 120 125Arg Arg Arg Ala Lys
Ala Leu Gly Ser Leu Thr Gln Met Glu Leu Leu 130 135 140Met Ile Ser
Ala Ala Leu Ala Glu Gly Trp Ala Val Ser Val Pro Asp145 150 155
160His Glu Gly Pro Lys Gly Leu Trp Gly Ser Pro Tyr Glu Pro Gly Tyr
165 170 175Arg Val Leu Asp Gly Ile Arg Ala Ala Leu Asn Ser Glu Arg
Val Gly 180 185 190Leu Ser Pro Ala Thr Pro Ile Gly Leu Trp Gly Tyr
Ser Gly Gly Gly 195 200 205Leu Ala Ser Ala Trp Ala Ala Glu Ala Cys
Gly Glu Tyr Ala Pro Asp 210 215 220Leu Asp Ile Val Gly Ala Val Leu
Gly Ser Pro Val Gly Asp Leu Gly225 230 235 240His Thr Phe Arg Arg
Leu Asn Gly Thr Leu Leu Ala Gly Leu Pro Ala 245 250 255Leu Val Val
Ala Ala Leu Gln His Ser Tyr Pro Gly Leu Ala Arg Val 260 265 270Ile
Lys Glu His Ala Asn Asp Glu Gly Arg Gln Leu Leu Glu Gln Leu 275 280
285Thr Glu Met Thr Thr Val Asp Ala Val Ile Arg Met Ala Gly Arg Asp
290 295 300Met Gly Asp Phe Leu Asp Glu Pro Leu Glu Asp Ile Leu Ser
Thr Pro305 310 315 320Glu Ile Ser His Val Phe Gly Asp Thr Lys Leu
Gly Ser Ala Val Pro 325 330 335Thr Pro Pro Val Leu Ile Val Gln Ala
Val His Asp Tyr Leu Ile Asp 340 345 350Val Ser Asp Ile Asp Ala Leu
Ala Asp Ser Tyr Thr Ala Gly Gly Ala 355 360 365Asn Val Thr Tyr His
Arg Asp Leu Phe Ser Glu His Val Ser Leu His 370 375 380Pro Leu Ser
Ala Pro Met Thr Leu Arg Trp Leu Thr Asp Arg Phe Ala385 390 395
400Gly Lys Pro Leu Thr Asp His Arg Val Arg Thr Thr Trp Pro Thr Ile
405 410 415Phe Asn Pro Met Thr Tyr Ala Gly Met Ala Arg Leu Ala Val
Ile Ala 420 425 430Ala Lys Val Ile Thr Gly Arg Lys Leu Ser Arg Arg
Pro Leu 435 440 4459210PRTMycobacterium tuberculosis 9Met Ile Ala
Thr Thr Arg Asp Arg Glu Gly Ala Thr Met Ile Thr Phe1 5 10 15Arg Leu
Arg Leu Pro Cys Arg Thr Ile Leu Arg Val Phe Ser Arg Asn 20 25 30Pro
Leu Val Arg Gly Thr Asp Arg Leu Glu Ala Val Val Met Leu Leu 35 40
45Ala Val Thr Val Ser Leu Leu Thr Ile Pro Phe Ala Ala Ala Ala Gly
50 55 60Thr Ala Val Gln Asp Ser Arg Ser His Val Tyr Ala His Gln Ala
Gln65 70 75 80Thr Arg His Pro Ala Thr Ala Thr Val Ile Asp His Glu
Gly Val Ile 85 90 95Asp Ser Asn Thr Thr Ala Thr Ser Ala Pro Pro Arg
Thr Lys Ile Thr 100 105 110Val Pro Ala Arg Trp Val Val Asn Gly Ile
Glu Arg Ser Gly Glu Val 115 120 125Asn Ala Lys Pro Gly Thr Lys Ser
Gly Asp Arg Val Gly Ile Trp Val 130 135 140Asp Ser Ala Gly Gln Leu
Val Asp Glu Pro Ala Pro Pro Ala Arg Ala145 150 155 160Ile Ala Asp
Ala Ala Leu Ala Ala Leu Gly Leu Trp Leu Ser Val Ala 165 170 175Ala
Val Ala Gly Ala Leu Leu Ala Leu Thr Arg Ala Ile Leu Ile Arg 180 185
190Val Arg Asn Ala Ser Trp Gln His Asp Ile Asp Ser Leu Phe Cys Thr
195 200 205Gln Arg 2101080PRTMycobacterium tuberculosis 10Met Thr
Asn Val Gly Asp Gln
Gly Val Asp Ala Val Phe Gly Val Ile1 5 10 15Tyr Pro Pro Gln Val Ala
Leu Val Ser Phe Gly Lys Pro Ala Gln Arg 20 25 30Val Cys Ala Val Asp
Gly Ala Ile His Val Met Thr Thr Val Leu Ala 35 40 45Thr Leu Pro Ala
Asp His Gly Cys Ser Asp Asp His Arg Gly Ala Leu 50 55 60Phe Phe Leu
Ser Ile Asn Glu Leu Thr Arg Cys Ala Ala Val Thr Gly65 70 75
8011652PRTMycobacterium tuberculosis 11Val Thr Val Thr Pro Arg Thr
Gly Ser Arg Ile Glu Glu Leu Leu Ala1 5 10 15Arg Ser Gly Arg Phe Phe
Ile Pro Gly Glu Ile Ser Ala Asp Leu Arg 20 25 30Thr Val Thr Arg Arg
Gly Gly Arg Asp Gly Asp Val Phe Tyr Arg Asp 35 40 45Arg Trp Ser His
Asp Lys Val Val Arg Ser Thr His Gly Val Asn Cys 50 55 60Thr Gly Ser
Cys Ser Trp Lys Ile Tyr Val Lys Asp Asp Ile Ile Thr65 70 75 80Trp
Glu Thr Gln Glu Thr Asp Tyr Pro Ser Val Gly Pro Asp Arg Pro 85 90
95Glu Tyr Glu Pro Arg Gly Cys Pro Arg Gly Ala Ala Phe Ser Trp Tyr
100 105 110Thr Tyr Ser Pro Thr Arg Val Arg His Pro Tyr Ala Arg Gly
Val Leu 115 120 125Val Glu Met Tyr Arg Glu Ala Lys Ala Arg Leu Gly
Asp Pro Val Ala 130 135 140Ala Trp Ala Asp Ile Gln Ala Asp Pro Arg
Arg Arg Arg Arg Tyr Gln145 150 155 160Arg Ala Arg Gly Lys Gly Gly
Leu Val Arg Val Ser Trp Ala Glu Ala 165 170 175Thr Glu Met Ile Ala
Ala Ala His Val His Thr Ile Ser Thr Tyr Gly 180 185 190Pro Asp Arg
Val Ala Gly Phe Ser Pro Ile Pro Ala Met Ser Met Val 195 200 205Ser
His Ala Ala Gly Ser Arg Phe Val Glu Leu Ile Gly Gly Val Met 210 215
220Thr Ser Phe Tyr Asp Trp Tyr Ala Asp Leu Pro Val Ala Ser Pro
Gln225 230 235 240Val Phe Gly Asp Gln Thr Asp Val Pro Glu Ser Gly
Asp Trp Trp Asp 245 250 255Val Val Trp Gln Cys Ala Ser Val Leu Leu
Thr Tyr Pro Asn Ser Arg 260 265 270Gln Leu Gly Thr Ala Glu Glu Leu
Leu Ala His Ile Asp Gly Pro Ala 275 280 285Ala Asp Leu Leu Gly Arg
Thr Val Ser Glu Leu Arg Arg Ala Asp Pro 290 295 300Leu Thr Ala Ala
Thr Arg Tyr Val Asp Thr Phe Asp Leu Arg Gly Arg305 310 315 320Ala
Thr Leu Tyr Leu Thr Tyr Trp Thr Ala Gly Asp Thr Arg Asn Arg 325 330
335Gly Arg Glu Met Leu Ala Phe Ala Gln Thr Tyr Arg Ser Thr Asp Val
340 345 350Ala Pro Pro Arg Gly Glu Thr Pro Asp Phe Leu Pro Val Val
Leu Glu 355 360 365Phe Ala Ala Thr Val Asp Pro Glu Ala Gly Arg Arg
Leu Leu Ser Gly 370 375 380Tyr Arg Val Pro Ile Ala Ala Leu Cys Asn
Ala Leu Thr Glu Ala Ala385 390 395 400Leu Pro Tyr Ala His Thr Val
Ala Ala Val Cys Arg Thr Gly Asp Met 405 410 415Met Gly Glu Leu Phe
Trp Thr Val Val Pro Tyr Val Thr Met Thr Ile 420 425 430Val Ala Val
Gly Ser Trp Trp Arg Tyr Arg Tyr Asp Lys Phe Gly Trp 435 440 445Thr
Thr Arg Ser Ser Gln Leu Tyr Glu Ser Arg Leu Leu Arg Ile Ala 450 455
460Ser Pro Met Phe His Phe Gly Ile Leu Val Val Ile Val Gly His
Gly465 470 475 480Ile Gly Leu Val Ile Pro Gln Ser Trp Thr Gln Ala
Ala Gly Leu Ser 485 490 495Glu Gly Ala Tyr His Val Gln Ala Val Val
Leu Gly Ser Ile Ala Gly 500 505 510Ile Thr Thr Leu Ala Gly Val Thr
Leu Leu Ile Tyr Arg Arg Arg Thr 515 520 525Arg Gly Pro Val Phe Met
Ala Thr Thr Val Asn Asp Lys Val Met Tyr 530 535 540Leu Val Leu Val
Ala Ala Ile Val Ala Gly Leu Gly Ala Thr Ala Leu545 550 555 560Gly
Ser Gly Val Val Gly Glu Ala Tyr Asn Tyr Arg Glu Thr Val Ser 565 570
575Val Trp Phe Arg Ser Val Trp Val Leu Gln Pro Arg Gly Asp Leu Met
580 585 590Ala Glu Ala Pro Leu Tyr Tyr Gln Ile His Val Leu Ile Gly
Leu Ala 595 600 605Leu Phe Ala Leu Trp Pro Phe Thr Arg Leu Val His
Ala Phe Ser Ala 610 615 620Pro Ile Gly Tyr Leu Phe Arg Pro Tyr Ile
Ile Tyr Arg Ser Arg Glu625 630 635 640Glu Leu Val Leu Thr Arg Pro
Arg Arg Arg Gly Trp 645 65012395PRTMycobacterium tuberculosis 12Met
Arg Gly Gln Ala Ala Asn Leu Val Leu Ala Thr Trp Ile Ser Val1 5 10
15Val Asn Phe Trp Ala Trp Asn Leu Ile Gly Pro Leu Ser Thr Ser Tyr
20 25 30Ala Arg Asp Met Ser Leu Ser Ser Ala Glu Ala Ser Leu Leu Val
Ala 35 40 45Thr Pro Ile Leu Val Gly Ala Leu Gly Arg Ile Val Thr Gly
Pro Leu 50 55 60Thr Asp Arg Phe Gly Gly Arg Ala Met Leu Ile Ala Val
Thr Leu Ala65 70 75 80Ser Ile Leu Pro Val Leu Ala Val Gly Val Ala
Ala Thr Met Gly Ser 85 90 95Tyr Ala Leu Leu Val Phe Phe Gly Leu Phe
Leu Gly Val Ala Gly Thr 100 105 110Ile Phe Ala Val Gly Ile Pro Phe
Ala Asn Asn Trp Tyr Gln Pro Ala 115 120 125Arg Arg Gly Phe Ser Thr
Gly Val Phe Gly Met Gly Met Val Gly Thr 130 135 140Ala Leu Ser Ala
Phe Phe Thr Pro Arg Phe Val Arg Trp Phe Gly Leu145 150 155 160Phe
Thr Thr His Ala Ile Val Ala Ala Ala Leu Ala Ser Thr Ala Val 165 170
175Val Ala Met Val Val Leu Arg Asp Ala Pro Tyr Phe Arg Pro Asn Ala
180 185 190Asp Pro Val Leu Pro Arg Leu Lys Ala Ala Ala Arg Leu Pro
Val Thr 195 200 205Trp Glu Met Ser Phe Leu Tyr Ala Ile Val Phe Gly
Gly Phe Val Ala 210 215 220Phe Ser Asn Tyr Leu Pro Thr Tyr Ile Thr
Thr Ile Tyr Gly Phe Ser225 230 235 240Thr Val Asp Ala Gly Ala Arg
Thr Ala Gly Phe Ala Leu Ala Ala Val 245 250 255Leu Ala Arg Pro Val
Gly Gly Trp Leu Ser Asp Arg Ile Ala Pro Arg 260 265 270His Val Val
Leu Ala Ser Leu Ala Gly Thr Ala Leu Leu Ala Phe Ala 275 280 285Ala
Ala Leu Gln Pro Pro Pro Glu Val Trp Ser Ala Ala Thr Phe Ile 290 295
300Thr Leu Ala Val Cys Leu Gly Val Gly Thr Gly Gly Val Phe Ala
Trp305 310 315 320Val Ala Arg Arg Ala Pro Ala Ala Ser Val Gly Ser
Val Thr Gly Ile 325 330 335Val Ala Ala Ala Gly Gly Leu Gly Gly Tyr
Phe Pro Pro Leu Val Met 340 345 350Gly Ala Thr Tyr Asp Pro Val Asp
Asn Asp Tyr Thr Val Gly Leu Leu 355 360 365Leu Leu Val Ala Thr Ala
Leu Val Ala Cys Thr Tyr Thr Ala Leu His 370 375 380Ala Arg Glu Pro
Val Ser Glu Glu Ala Ser Arg385 390 3951394PRTMycobacterium
tuberculosis 13Met Cys Gly Asp Gln Ser Asp His Val Leu Gln His Trp
Thr Val Asp1 5 10 15Ile Ser Ile Asp Glu His Glu Gly Leu Thr Arg Ala
Lys Ala Arg Leu 20 25 30Arg Trp Arg Glu Lys Glu Leu Val Gly Val Gly
Leu Ala Arg Leu Asn 35 40 45Pro Ala Asp Arg Asn Val Pro Glu Ile Gly
Asp Glu Leu Ser Val Ala 50 55 60Arg Ala Leu Ser Asp Leu Gly Lys Arg
Met Leu Lys Val Ser Thr His65 70 75 80Asp Ile Glu Ala Val Thr His
Gln Pro Ala Arg Leu Leu Tyr 85 9014560PRTMycobacterium tuberculosis
14Met Ile Pro Thr Met Thr Ser Ala Gly Trp Ala Pro Gly Val Val Gln1
5 10 15Phe Arg Glu Tyr Gln Arg Arg Trp Leu Arg Gly Asp Val Leu Ala
Gly 20 25 30Leu Thr Val Ala Ala Tyr Leu Ile Pro Gln Ala Met Ala Tyr
Ala Thr 35 40 45Val Ala Gly Leu Pro Pro Ala Ala Gly Leu Trp Ala Ser
Ile Ala Pro 50 55 60Leu Ala Ile Tyr Ala Leu Leu Gly Ser Ser Arg Gln
Leu Ser Ile Gly65 70 75 80Pro Glu Ser Ala Thr Ala Leu Met Thr Ala
Ala Val Leu Ala Pro Met 85 90 95Ala Ala Gly Asp Leu Arg Arg Tyr Ala
Val Leu Ala Ala Thr Leu Gly 100 105 110Leu Leu Val Gly Leu Ile Cys
Leu Leu Ala Gly Thr Ala Arg Leu Gly 115 120 125Phe Leu Ala Ser Leu
Arg Ser Arg Pro Val Leu Val Gly Tyr Met Ala 130 135 140Gly Ile Ala
Leu Val Met Ile Ser Ser Gln Leu Gly Thr Ile Thr Gly145 150 155
160Thr Ser Val Glu Gly Asn Glu Phe Phe Ser Glu Val His Ser Phe Ala
165 170 175Thr Ser Val Thr Arg Val His Trp Pro Thr Phe Val Leu Ala
Met Ser 180 185 190Val Leu Ala Leu Leu Thr Met Leu Thr Arg Trp Ala
Pro Arg Ala Pro 195 200 205Gly Pro Ile Ile Ala Val Leu Ala Ala Thr
Met Leu Val Ala Val Met 210 215 220Ser Leu Asp Ala Lys Gly Ile Ala
Ile Val Gly Arg Ile Pro Ser Gly225 230 235 240Leu Pro Thr Pro Gly
Val Pro Pro Val Ser Val Glu Asp Leu Arg Ala 245 250 255Leu Ile Ile
Pro Ala Ala Gly Ile Ala Ile Val Thr Phe Thr Asp Gly 260 265 270Val
Leu Thr Ala Arg Ala Phe Ala Ala Arg Arg Gly Gln Glu Val Asn 275 280
285Ala Asn Ala Glu Leu Arg Ala Val Gly Ala Cys Asn Ile Ala Ala Gly
290 295 300Leu Thr His Gly Phe Pro Val Ser Ser Ser Ser Ser Arg Thr
Ala Leu305 310 315 320Ala Asp Val Val Gly Gly Arg Thr Gln Leu Tyr
Ser Leu Ile Ala Leu 325 330 335Gly Leu Val Val Ile Val Met Val Phe
Ala Ser Gly Leu Leu Ala Met 340 345 350Phe Pro Ile Ala Ala Leu Gly
Ala Leu Val Val Tyr Ala Ala Leu Arg 355 360 365Leu Ile Asp Leu Ser
Glu Phe Arg Arg Leu Ala Arg Phe Arg Arg Ser 370 375 380Glu Leu Met
Leu Ala Leu Ala Thr Thr Ala Ala Val Leu Gly Leu Gly385 390 395
400Val Phe Tyr Gly Val Leu Ala Ala Val Ala Leu Ser Ile Leu Glu Leu
405 410 415Leu Arg Arg Val Ala His Pro His Asp Ser Val Leu Gly Phe
Val Pro 420 425 430Gly Ile Ala Gly Met His Asp Ile Asp Asp Tyr Pro
Gln Ala Lys Arg 435 440 445Val Pro Gly Leu Val Val Tyr Arg Tyr Asp
Ala Pro Leu Cys Phe Ala 450 455 460Asn Ala Glu Asp Phe Arg Arg Arg
Ala Leu Thr Val Val Asp Gln Asp465 470 475 480Pro Gly Gln Val Glu
Trp Phe Val Leu Asn Ala Glu Ser Asn Val Glu 485 490 495Val Asp Leu
Thr Ala Leu Asp Ala Leu Asp Gln Leu Arg Thr Glu Leu 500 505 510Leu
Arg Arg Gly Ile Val Phe Ala Met Ala Arg Val Lys Gln Asp Leu 515 520
525Arg Glu Ser Leu Arg Ala Ala Ser Leu Leu Asp Lys Ile Gly Glu Asp
530 535 540His Ile Phe Met Thr Leu Pro Thr Ala Val Gln Ala Phe Arg
Arg Arg545 550 555 56015143PRTMycobacterium tuberculosis 15Met Ile
Thr Asn Leu Arg Arg Arg Thr Ala Met Ala Ala Ala Gly Leu1 5 10 15Gly
Ala Ala Leu Gly Leu Gly Ile Leu Leu Val Pro Thr Val Asp Ala 20 25
30His Leu Ala Asn Gly Ser Met Ser Glu Val Met Met Ser Glu Ile Ala
35 40 45Gly Leu Pro Ile Pro Pro Ile Ile His Tyr Gly Ala Ile Ala Tyr
Ala 50 55 60Pro Ser Gly Ala Ser Gly Lys Ala Trp His Gln Arg Thr Pro
Ala Arg65 70 75 80Ala Glu Gln Val Ala Leu Glu Lys Cys Gly Asp Lys
Thr Cys Lys Val 85 90 95Val Ser Arg Phe Thr Arg Cys Gly Ala Val Ala
Tyr Asn Gly Ser Lys 100 105 110Tyr Gln Gly Gly Thr Gly Leu Thr Arg
Arg Ala Ala Glu Asp Asp Ala 115 120 125Val Asn Arg Leu Glu Gly Gly
Arg Ile Val Asn Trp Ala Cys Asn 130 135 14016905PRTMycobacterium
tuberculosis 16Leu Ser Ala Ser Val Ser Ala Thr Thr Ala His His Gly
Leu Pro Ala1 5 10 15His Glu Val Val Leu Leu Leu Glu Ser Asp Pro Tyr
His Gly Leu Ser 20 25 30Asp Gly Glu Ala Ala Gln Arg Leu Glu Arg Phe
Gly Pro Asn Thr Leu 35 40 45Ala Val Val Thr Arg Ala Ser Leu Leu Ala
Arg Ile Leu Arg Gln Phe 50 55 60His His Pro Leu Ile Tyr Val Leu Leu
Val Ala Gly Thr Ile Thr Ala65 70 75 80Gly Leu Lys Glu Phe Val Asp
Ala Ala Val Ile Phe Gly Val Val Val 85 90 95Ile Asn Ala Ile Val Gly
Phe Ile Gln Glu Ser Lys Ala Glu Ala Ala 100 105 110Leu Gln Gly Leu
Arg Ser Met Val His Thr His Ala Lys Val Val Arg 115 120 125Glu Gly
His Glu His Thr Met Pro Ser Glu Glu Leu Val Pro Gly Asp 130 135
140Leu Val Leu Leu Ala Ala Gly Asp Lys Val Pro Ala Asp Leu Arg
Leu145 150 155 160Val Arg Gln Thr Gly Leu Ser Val Asn Glu Ser Ala
Leu Thr Gly Glu 165 170 175Ser Thr Pro Val His Lys Asp Glu Val Ala
Leu Pro Glu Gly Thr Pro 180 185 190Val Ala Asp Arg Arg Asn Ile Ala
Tyr Ser Gly Thr Leu Val Thr Ala 195 200 205Gly His Gly Ala Gly Ile
Val Val Ala Thr Gly Ala Glu Thr Glu Leu 210 215 220Gly Glu Ile His
Arg Leu Val Gly Ala Ala Glu Val Val Ala Thr Pro225 230 235 240Leu
Thr Ala Lys Leu Ala Trp Phe Ser Lys Phe Leu Thr Ile Ala Ile 245 250
255Leu Gly Leu Ala Ala Leu Thr Phe Gly Val Gly Leu Leu Arg Arg Gln
260 265 270Asp Ala Val Glu Thr Phe Thr Ala Ala Ile Ala Leu Ala Val
Gly Ala 275 280 285Ile Pro Glu Gly Leu Pro Thr Ala Val Thr Ile Thr
Leu Ala Ile Gly 290 295 300Met Ala Arg Met Ala Lys Arg Arg Ala Val
Ile Arg Arg Leu Pro Ala305 310 315 320Val Glu Thr Leu Gly Ser Thr
Thr Val Ile Cys Ala Asp Lys Thr Gly 325 330 335Thr Leu Thr Glu Asn
Gln Met Thr Val Gln Ser Ile Trp Thr Pro His 340 345 350Gly Glu Ile
Arg Ala Thr Gly Thr Gly Tyr Ala Pro Asp Val Leu Leu 355 360 365Cys
Asp Thr Asp Asp Ala Pro Val Pro Val Asn Ala Asn Ala Ala Leu 370 375
380Arg Trp Ser Leu Leu Ala Gly Ala Cys Ser Asn Asp Ala Ala Leu
Val385 390 395 400Arg Asp Gly Thr Arg Trp Gln Ile Val Gly Asp Pro
Thr Glu Gly Ala 405 410 415Met Leu Val Val Ala Ala Lys Ala Gly Phe
Asn Pro Glu Arg Leu Ala 420 425 430Thr Thr Leu Pro Gln Val Ala Ala
Ile Pro Phe Ser Ser Glu Arg Gln 435 440 445Tyr Met Ala Thr Leu His
Arg Asp Gly Thr Asp His Val Val Leu Ala 450 455 460Lys Gly Ala Val
Glu Arg Met Leu Asp Leu Cys Gly Thr Glu Met Gly465 470 475 480Ala
Asp Gly Ala Leu Arg Pro Leu Asp Arg Ala Thr Val Leu Arg Ala 485 490
495Thr Glu Met Leu Thr Ser Arg Gly Leu Arg Val Leu Ala Thr Gly Met
500 505 510Gly Ala Gly Ala Gly Thr Pro Asp Asp Phe Asp Glu Asn Val
Ile Pro 515 520 525Gly
Ser Leu Ala Leu Thr Gly Leu Gln Ala Met Ser Asp Pro Pro Arg 530 535
540Ala Ala Ala Ala Ser Ala Val Ala Ala Cys His Ser Ala Gly Ile
Ala545 550 555 560Val Lys Met Ile Thr Gly Asp His Ala Gly Thr Ala
Thr Ala Ile Ala 565 570 575Thr Glu Val Gly Leu Leu Asp Asn Thr Glu
Pro Ala Ala Gly Ser Val 580 585 590Leu Thr Gly Ala Glu Leu Ala Ala
Leu Ser Ala Asp Gln Tyr Pro Glu 595 600 605Ala Val Asp Thr Ala Ser
Val Phe Ala Arg Val Ser Pro Glu Gln Lys 610 615 620Leu Arg Leu Val
Gln Ala Leu Gln Ala Arg Gly His Val Val Ala Met625 630 635 640Thr
Gly Asp Gly Val Asn Asp Ala Pro Ala Leu Arg Gln Ala Asn Ile 645 650
655Gly Val Ala Met Gly Arg Gly Gly Thr Glu Val Ala Lys Asp Ala Ala
660 665 670Asp Met Val Leu Thr Asp Asp Asp Phe Ala Thr Ile Glu Ala
Ala Val 675 680 685Glu Glu Gly Arg Gly Val Phe Asp Asn Leu Thr Lys
Phe Ile Thr Trp 690 695 700Thr Leu Pro Thr Asn Leu Gly Glu Gly Leu
Val Ile Leu Ala Ala Ile705 710 715 720Ala Val Gly Val Ala Leu Pro
Ile Leu Pro Thr Gln Ile Leu Trp Ile 725 730 735Asn Met Thr Thr Ala
Ile Ala Leu Gly Leu Met Leu Ala Phe Glu Pro 740 745 750Lys Glu Ala
Gly Ile Met Thr Arg Pro Pro Arg Asp Pro Asp Gln Pro 755 760 765Leu
Leu Thr Gly Trp Leu Val Arg Arg Thr Leu Leu Val Ser Thr Leu 770 775
780Leu Val Ala Ser Ala Trp Trp Leu Phe Ala Trp Glu Leu Asp Asn
Gly785 790 795 800Ala Gly Leu His Glu Ala Arg Thr Ala Ala Leu Asn
Leu Phe Val Val 805 810 815Val Glu Ala Phe Tyr Leu Phe Ser Cys Arg
Ser Leu Thr Arg Ser Ala 820 825 830Trp Arg Leu Gly Met Phe Ala Asn
Arg Trp Ile Ile Leu Gly Val Ser 835 840 845Ala Gln Ala Ile Ala Gln
Phe Ala Ile Thr Tyr Leu Pro Ala Met Asn 850 855 860Met Val Phe Asp
Thr Ala Pro Ile Asp Ile Gly Val Trp Val Arg Ile865 870 875 880Phe
Ala Val Ala Thr Ala Ile Thr Ile Val Val Ala Thr Asp Thr Leu 885 890
895Leu Pro Arg Ile Arg Ala Gln Pro Pro 900 90517258PRTMycobacterium
tuberculosis 17Met Ser Phe His Asp Leu His His Gln Gly Val Pro Phe
Val Leu Pro1 5 10 15Asn Ala Trp Asp Val Pro Ser Ala Leu Ala Tyr Leu
Ala Glu Gly Phe 20 25 30Thr Ala Ile Gly Thr Thr Ser Phe Gly Val Ser
Ser Ser Gly Gly His 35 40 45Pro Asp Gly His Arg Ala Thr Arg Gly Ala
Asn Ile Ala Leu Ala Ala 50 55 60Ala Leu Ala Pro Leu Gln Cys Tyr Val
Ser Val Asp Ile Glu Asp Gly65 70 75 80Tyr Ser Asp Glu Pro Asp Ala
Ile Ala Asp Tyr Val Ala Gln Leu Ser 85 90 95Thr Ala Gly Ile Asn Ile
Glu Asp Ser Ser Ala Glu Lys Leu Ile Asp 100 105 110Pro Ala Leu Ala
Ala Ala Lys Ile Val Ala Ile Lys Gln Arg Asn Pro 115 120 125Glu Val
Phe Val Asn Ala Arg Val Asp Thr Tyr Trp Leu Arg Gln His 130 135
140Ala Asp Thr Thr Ser Thr Ile Gln Arg Ala Leu Arg Tyr Val Asp
Ala145 150 155 160Gly Ala Asp Gly Val Phe Val Pro Leu Ala Asn Asp
Pro Asp Glu Leu 165 170 175Ala Glu Leu Thr Arg Asn Ile Pro Cys Pro
Val Asn Thr Leu Pro Val 180 185 190Pro Gly Leu Thr Ile Ala Asp Leu
Gly Glu Leu Gly Val Ala Arg Val 195 200 205Ser Thr Gly Ser Val Pro
Tyr Ser Ala Gly Leu Tyr Ala Ala Ala His 210 215 220Ala Ala Arg Ala
Val Ser Asp Gly Glu Gln Leu Pro Arg Ser Val Pro225 230 235 240Tyr
Ala Glu Leu Gln Ala Arg Leu Val Asp Tyr Glu Asn Arg Thr Ser 245 250
255Thr Thr18285PRTMycobacterium tuberculosis 18Val Val Lys Arg Ser
Arg Ala Thr Arg Leu Ser Pro Ser Ile Trp Ser1 5 10 15Gly Trp Glu Ser
Pro Gln Cys Arg Ser Ile Arg Ala Arg Leu Leu Leu 20 25 30Pro Arg Gly
Arg Ser Arg Pro Pro Asn Ala Asp Cys Cys Trp Asn Gln 35 40 45Leu Ala
Val Thr Pro Asp Thr Arg Met Pro Ala Ser Ser Ala Ala Gly 50 55 60Arg
Asp Ala Ala Ala Tyr Asp Ala Trp Tyr Asp Ser Pro Thr Gly Arg65 70 75
80Pro Ile Leu Ala Thr Glu Val Ala Ala Leu Arg Pro Leu Ile Glu Val
85 90 95Phe Ala Gln Pro Arg Leu Glu Ile Gly Val Gly Thr Gly Arg Phe
Ala 100 105 110Asp Leu Leu Gly Val Arg Phe Gly Leu Asp Pro Ser Arg
Asp Ala Leu 115 120 125Met Phe Ala Arg Arg Arg Gly Val Leu Val Ala
Asn Ala Val Gly Glu 130 135 140Ala Val Pro Phe Val Ser Arg His Phe
Gly Ala Val Leu Met Ala Phe145 150 155 160Thr Leu Cys Phe Val Thr
Asp Pro Ala Ala Ile Phe Arg Glu Thr Arg 165 170 175Arg Leu Leu Ala
Asp Gly Gly Gly Leu Val Ile Gly Phe Leu Pro Arg 180 185 190Gly Thr
Pro Trp Ala Asp Leu Tyr Ala Leu Arg Ala Ala Arg Gly Gln 195 200
205Pro Gly Tyr Arg Asp Ala Arg Phe Tyr Thr Ala Ala Glu Leu Glu Gln
210 215 220Leu Leu Ala Asp Ser Gly Phe Arg Val Ile Ala Arg Arg Cys
Thr Leu225 230 235 240His Gln Pro Pro Gly Leu Ala Arg Tyr Asp Ile
Glu Ala Ala His Asp 245 250 255Gly Ile Gln Ala Gly Ala Gly Phe Val
Ala Ile Ser Ala Val Asp Gln 260 265 270Ala His Glu Pro Lys Asp Asp
His Pro Leu Glu Ser Glu 275 280 28519285PRTMycobacterium
tuberculosis 19Val Val Lys Arg Ser Arg Ala Thr Arg Leu Ser Pro Ser
Ile Trp Ser1 5 10 15Gly Trp Glu Ser Pro Gln Cys Arg Ser Ile Arg Ala
Arg Leu Leu Leu 20 25 30Pro Arg Gly Arg Ser Arg Pro Pro Asn Ala Asp
Cys Cys Trp Asn Gln 35 40 45Leu Ala Val Thr Pro Asp Thr Arg Met Pro
Ala Ser Ser Ala Ala Gly 50 55 60Arg Asp Ala Ala Ala Tyr Asp Ala Trp
Tyr Asp Ser Pro Thr Gly Arg65 70 75 80Pro Ile Leu Ala Thr Glu Val
Ala Ala Leu Arg Pro Leu Ile Glu Val 85 90 95Phe Ala Gln Pro Arg Leu
Glu Ile Gly Val Gly Thr Gly Arg Phe Ala 100 105 110Asp Leu Leu Gly
Val Arg Phe Gly Leu Asp Pro Ser Arg Asp Ala Leu 115 120 125Met Phe
Ala Arg Arg Arg Gly Val Leu Val Ala Asn Ala Val Gly Glu 130 135
140Ala Val Pro Phe Val Ser Arg His Phe Gly Ala Val Leu Met Ala
Phe145 150 155 160Thr Leu Cys Phe Val Thr Asp Pro Ala Ala Ile Phe
Arg Glu Thr Arg 165 170 175Arg Leu Leu Ala Asp Gly Gly Gly Leu Val
Ile Gly Phe Leu Pro Arg 180 185 190Gly Thr Pro Trp Ala Asp Leu Tyr
Ala Leu Arg Ala Ala Arg Gly Gln 195 200 205Pro Gly Tyr Arg Asp Ala
Arg Phe Tyr Thr Ala Ala Glu Leu Glu Gln 210 215 220Leu Leu Ala Asp
Ser Gly Phe Arg Val Ile Ala Arg Arg Cys Thr Leu225 230 235 240His
Gln Pro Pro Gly Leu Ala Arg Tyr Asp Ile Glu Ala Ala His Asp 245 250
255Gly Ile Gln Ala Gly Ala Gly Phe Val Ala Ile Ser Ala Val Asp Gln
260 265 270Ala His Glu Pro Lys Asp Asp His Pro Leu Glu Ser Glu 275
280 28520114PRTMycobacterium tuberculosis 20Val Thr Tyr Val Ile Gly
Ser Glu Cys Val Asp Val Met Asp Lys Ser1 5 10 15Cys Val Gln Glu Cys
Pro Val Asp Cys Ile Tyr Glu Gly Ala Arg Met 20 25 30Leu Tyr Ile Asn
Pro Asp Glu Cys Val Asp Cys Gly Ala Cys Lys Pro 35 40 45Ala Cys Arg
Val Glu Ala Ile Tyr Trp Glu Gly Asp Leu Pro Asp Asp 50 55 60Gln His
Gln His Leu Gly Asp Asn Ala Ala Phe Phe His Gln Val Leu65 70 75
80Pro Gly Arg Val Ala Pro Leu Gly Ser Pro Gly Gly Ala Ala Ala Val
85 90 95Gly Pro Ile Gly Val Asp Thr Pro Leu Val Ala Ala Ile Pro Val
Glu 100 105 110Cys Pro21279PRTMycobacterium tuberculosis 21Met Asn
Gln Ser His Lys Pro Pro Ser Ile Val Val Gly Ile Asp Gly1 5 10 15Ser
Lys Pro Ala Val Gln Ala Ala Leu Trp Ala Val Asp Glu Ala Ala 20 25
30Ser Arg Asp Ile Pro Leu Arg Leu Leu Tyr Ala Ile Glu Pro Asp Asp
35 40 45Pro Gly Tyr Ala Ala His Gly Ala Ala Ala Arg Lys Leu Ala Ala
Ala 50 55 60Glu Asn Ala Val Arg Tyr Ala Phe Thr Ala Val Glu Ala Ala
Asp Arg65 70 75 80Pro Val Lys Val Glu Val Glu Ile Thr Gln Glu Arg
Pro Val Thr Ser 85 90 95Leu Ile Arg Ala Ser Ala Ala Ala Ala Leu Val
Cys Val Gly Ala Ile 100 105 110Gly Val His His Phe Arg Pro Glu Arg
Val Gly Ser Thr Ala Ala Ala 115 120 125Leu Ala Leu Ser Ala Gln Cys
Pro Val Ala Ile Val Arg Pro His Arg 130 135 140Val Pro Ile Gly Arg
Asp Ala Ala Trp Ile Val Val Glu Ala Asp Gly145 150 155 160Ser Ser
Asp Ile Gly Val Leu Leu Gly Ala Val Met Ala Glu Ala Arg 165 170
175Leu Arg Asp Ser Pro Val Arg Val Val Thr Cys Arg Gln Ser Gly Val
180 185 190Gly Asp Thr Gly Asp Asp Val Arg Ala Ser Leu Asp Arg Trp
Leu Ala 195 200 205Arg Trp Gln Pro Arg Tyr Pro Asp Val Arg Val Gln
Ser Ala Ala Val 210 215 220His Gly Glu Leu Leu Asp Tyr Leu Ala Gly
Leu Gly Arg Ser Val His225 230 235 240Met Val Val Leu Ser Ala Ser
Asp Gln Glu His Val Glu Gln Leu Val 245 250 255Gly Ala Pro Gly Asn
Ala Val Leu Gln Glu Ala Gly Cys Thr Leu Leu 260 265 270Val Val Gly
Gln Gln Tyr Leu 27522339PRTMycobacterium tuberculosis 22Met Thr Glu
Pro Ala Ala Trp Asp Glu Gly Lys Pro Arg Ile Ile Thr1 5 10 15Leu Thr
Met Asn Pro Ala Leu Asp Ile Thr Thr Ser Val Asp Val Val 20 25 30Arg
Pro Thr Glu Lys Met Arg Cys Gly Ala Pro Arg Tyr Asp Pro Gly 35 40
45Gly Gly Gly Ile Asn Val Ala Arg Ile Val His Val Leu Gly Gly Cys
50 55 60Ser Thr Ala Leu Phe Pro Ala Gly Gly Ser Thr Gly Ser Leu Leu
Met65 70 75 80Ala Leu Leu Gly Asp Ala Gly Val Pro Phe Arg Val Ile
Pro Ile Ala 85 90 95Ala Ser Thr Arg Glu Ser Phe Thr Val Asn Glu Ser
Arg Thr Ala Lys 100 105 110Gln Tyr Arg Phe Val Leu Pro Gly Pro Ser
Leu Thr Val Ala Glu Gln 115 120 125Glu Gln Cys Leu Asp Glu Leu Arg
Gly Ala Ala Ala Ser Ala Ala Phe 130 135 140Val Val Ala Ser Gly Ser
Leu Pro Pro Gly Val Ala Ala Asp Tyr Tyr145 150 155 160Gln Arg Val
Ala Asp Ile Cys Arg Arg Ser Ser Thr Pro Leu Ile Leu 165 170 175Asp
Thr Ser Gly Gly Gly Leu Gln His Ile Ser Ser Gly Val Phe Leu 180 185
190Leu Lys Ala Ser Val Arg Glu Leu Arg Glu Cys Val Gly Ser Glu Leu
195 200 205Leu Thr Glu Pro Glu Gln Leu Ala Ala Ala His Glu Leu Ile
Asp Arg 210 215 220Gly Arg Ala Glu Val Val Val Val Ser Leu Gly Ser
Gln Gly Ala Leu225 230 235 240Leu Ala Thr Arg His Ala Ser His Arg
Phe Ser Ser Ile Pro Met Thr 245 250 255Ala Val Ser Gly Val Gly Ala
Gly Asp Ala Met Val Ala Ala Ile Thr 260 265 270Val Gly Leu Ser Arg
Gly Trp Ser Leu Ile Lys Ser Val Arg Leu Gly 275 280 285Asn Ala Ala
Gly Ala Ala Met Leu Leu Thr Pro Gly Thr Ala Ala Cys 290 295 300Asn
Arg Asp Asp Val Glu Arg Phe Phe Glu Leu Ala Ala Glu Pro Thr305 310
315 320Glu Val Gly Gln Asp Gln Tyr Val Trp His Pro Ile Val Asn Pro
Glu 325 330 335Ala Ser Pro23681PRTMycobacterium tuberculosis 23Val
Leu Met Thr Ala Ala Ala Asp Val Thr Arg Arg Ser Pro Arg Arg1 5 10
15Val Phe Arg Asp Arg Arg Glu Ala Gly Arg Val Leu Ala Glu Leu Leu
20 25 30Ala Ala Tyr Arg Asp Gln Pro Asp Val Ile Val Leu Gly Leu Ala
Arg 35 40 45Gly Gly Leu Pro Val Ala Trp Glu Val Ala Ala Ala Leu His
Ala Pro 50 55 60Leu Asp Ala Phe Val Val Arg Lys Leu Gly Ala Pro Gly
His Asp Glu65 70 75 80Phe Ala Val Gly Ala Leu Ala Ser Gly Gly Arg
Val Val Val Asn Asp 85 90 95Asp Val Val Arg Gly Leu Arg Ile Thr Pro
Gln Gln Leu Arg Asp Ile 100 105 110Ala Glu Arg Glu Gly Arg Glu Leu
Leu Arg Arg Glu Ser Ala Tyr Arg 115 120 125Gly Glu Arg Pro Pro Thr
Asp Ile Thr Gly Lys Thr Val Ile Val Val 130 135 140Asp Asp Gly Leu
Ala Thr Gly Ala Ser Met Phe Ala Ala Val Gln Ala145 150 155 160Leu
Arg Asp Ala Gln Pro Ala Gln Ile Val Ile Ala Val Pro Ala Ala 165 170
175Pro Glu Ser Thr Cys Arg Glu Phe Ala Gly Leu Val Asp Asp Val Val
180 185 190Cys Ala Thr Met Pro Thr Pro Phe Leu Ala Val Gly Glu Ser
Phe Trp 195 200 205Asp Phe Arg Gln Val Thr Asp Glu Glu Val Arg Arg
Leu Leu Ala Thr 210 215 220Pro Thr Ala Gly Pro Ser Leu Arg Arg Pro
Ala Ala Ser Thr Ala Ala225 230 235 240Asp Val Leu Arg Arg Val Ala
Ile Asp Ala Pro Gly Gly Val Pro Thr 245 250 255His Glu Val Leu Ala
Glu Leu Val Gly Asp Ala Arg Ile Val Leu Ile 260 265 270Gly Glu Ser
Ser His Gly Thr His Glu Phe Tyr Gln Ala Arg Ala Ala 275 280 285Met
Thr Gln Trp Leu Ile Glu Glu Lys Gly Phe Gly Ala Val Ala Ala 290 295
300Glu Ala Asp Trp Pro Asp Ala Tyr Arg Val Asn Arg Tyr Val Arg
Gly305 310 315 320Leu Gly Glu Asp Thr Asn Ala Asp Glu Ala Leu Ser
Gly Phe Glu Arg 325 330 335Phe Pro Ala Trp Met Trp Arg Asn Thr Val
Val Arg Asp Phe Val Glu 340 345 350Trp Leu Arg Thr Arg Asn Gln Arg
Tyr Glu Ser Gly Ala Leu Arg Gln 355 360 365Ala Gly Phe Tyr Gly Leu
Asp Leu Tyr Ser Leu His Arg Ser Ile Gln 370 375 380Glu Val Ile Ser
Tyr Leu Asp Lys Val Asp Pro Arg Ala Ala Ala Arg385 390 395 400Ala
Arg Ala Arg Tyr Ala Cys Phe Asp His Ala Cys Ala Asp Asp Gly 405 410
415Gln Ala Tyr Gly Phe Ala Ala Ala Phe Gly Ala Gly Pro Ser Cys Glu
420 425 430Arg Glu Ala Val Glu Gln Leu Val Asp Val Gln Arg Asn Ala
Leu Ala 435 440 445Tyr Ala Arg Gln Asp Gly Leu Leu Ala Glu Asp Glu
Leu Phe Tyr Ala 450 455 460Gln Gln Asn Ala Gln Thr Val Arg Asp Ala
Glu Val Tyr Tyr Arg Ala465 470 475 480Met Phe Ser Gly Arg Val Thr
Ser Trp Asn Leu Arg Asp Gln His Met 485 490 495Ala Gln Thr Leu Gly
Ser Leu Leu Thr His Leu Asp
Arg His Leu Asp 500 505 510Ala Pro Pro Ala Arg Ile Val Val Trp Ala
His Asn Ser His Val Gly 515 520 525Asp Ala Arg Ala Thr Glu Val Trp
Ala Asp Gly Gln Leu Thr Leu Gly 530 535 540Gln Ile Val Arg Glu Arg
Tyr Gly Asp Glu Ser Arg Ser Ile Gly Phe545 550 555 560Ser Thr Tyr
Thr Gly Thr Val Thr Ala Ala Ser Glu Trp Gly Gly Ile 565 570 575Ala
Gln Arg Lys Ala Val Arg Pro Ala Leu His Gly Ser Val Glu Glu 580 585
590Leu Phe His Gln Thr Ala Asp Ser Phe Leu Val Ser Ala Arg Leu Ser
595 600 605Arg Asp Ala Glu Ala Pro Leu Asp Val Val Arg Leu Gly Arg
Ala Ile 610 615 620Gly Val Val Tyr Leu Pro Ala Thr Glu Arg Gln Ser
His Tyr Leu His625 630 635 640Val Arg Pro Ala Asp Gln Phe Asp Ala
Met Ile His Ile Asp Gln Thr 645 650 655Arg Ala Leu Glu Pro Leu Glu
Val Thr Ser Arg Trp Ile Ala Gly Glu 660 665 670Asn Pro Glu Thr Tyr
Pro Thr Gly Leu 675 68024144PRTMycobacterium tuberculosis 24Met Ala
Thr Thr Leu Pro Val Gln Arg His Pro Arg Ser Leu Phe Pro1 5 10 15Glu
Phe Ser Glu Leu Phe Ala Ala Phe Pro Ser Phe Ala Gly Leu Arg 20 25
30Pro Thr Phe Asp Thr Arg Leu Met Arg Leu Glu Asp Glu Met Lys Glu
35 40 45Gly Arg Tyr Glu Val Arg Ala Glu Leu Pro Gly Val Asp Pro Asp
Lys 50 55 60Asp Val Asp Ile Met Val Arg Asp Gly Gln Leu Thr Ile Lys
Ala Glu65 70 75 80Arg Thr Glu Gln Lys Asp Phe Asp Gly Arg Ser Glu
Phe Ala Tyr Gly 85 90 95Ser Phe Val Arg Thr Val Ser Leu Pro Val Gly
Ala Asp Glu Asp Asp 100 105 110Ile Lys Ala Thr Tyr Asp Lys Gly Ile
Leu Thr Val Ser Val Ala Val 115 120 125Ser Glu Gly Lys Pro Thr Glu
Lys His Ile Gln Ile Arg Ser Thr Asn 130 135
14025331PRTMycobacterium tuberculosis 25Met Pro Asp Thr Met Val Thr
Thr Asp Val Ile Lys Ser Ala Val Gln1 5 10 15Leu Ala Cys Arg Ala Pro
Ser Leu His Asn Ser Gln Pro Trp Arg Trp 20 25 30Ile Ala Glu Asp His
Thr Val Ala Leu Phe Leu Asp Lys Asp Arg Val 35 40 45Leu Tyr Ala Thr
Asp His Ser Gly Arg Glu Ala Leu Leu Gly Cys Gly 50 55 60Ala Val Leu
Asp His Phe Arg Val Ala Met Ala Ala Ala Gly Thr Thr65 70 75 80Ala
Asn Val Glu Arg Phe Pro Asn Pro Asn Asp Pro Leu His Leu Ala 85 90
95Ser Ile Asp Phe Ser Pro Ala Asp Phe Val Thr Glu Gly His Arg Leu
100 105 110Arg Ala Asp Ala Ile Leu Leu Arg Arg Thr Asp Arg Leu Pro
Phe Ala 115 120 125Glu Pro Pro Asp Trp Asp Leu Val Glu Ser Gln Leu
Arg Thr Thr Val 130 135 140Thr Ala Asp Thr Val Arg Ile Asp Val Ile
Ala Asp Asp Met Arg Pro145 150 155 160Glu Leu Ala Ala Ala Ser Lys
Leu Thr Glu Ser Leu Arg Leu Tyr Asp 165 170 175Ser Ser Tyr His Ala
Glu Leu Phe Trp Trp Thr Gly Ala Phe Glu Thr 180 185 190Ser Glu Gly
Ile Pro His Ser Ser Leu Val Ser Ala Ala Glu Ser Asp 195 200 205Arg
Val Thr Phe Gly Arg Asp Phe Pro Val Val Ala Asn Thr Asp Arg 210 215
220Arg Pro Glu Phe Gly His Asp Arg Ser Lys Val Leu Val Leu Ser
Thr225 230 235 240Tyr Asp Asn Glu Arg Ala Ser Leu Leu Arg Cys Gly
Glu Met Leu Ser 245 250 255Ala Val Leu Leu Asp Ala Thr Met Ala Gly
Leu Ala Thr Cys Thr Leu 260 265 270Thr His Ile Thr Glu Leu His Ala
Ser Arg Asp Leu Val Ala Ala Leu 275 280 285Ile Gly Gln Pro Ala Thr
Pro Gln Ala Leu Val Arg Val Gly Leu Ala 290 295 300Pro Glu Met Glu
Glu Pro Pro Pro Ala Thr Pro Arg Arg Pro Ile Asp305 310 315 320Glu
Val Phe His Val Arg Ala Lys Asp His Arg 325
33026195PRTMycobacterium tuberculosis 26Met Pro Leu Leu Thr Ile Gly
Asp Gln Phe Pro Ala Tyr Gln Leu Thr1 5 10 15Ala Leu Ile Gly Gly Asp
Leu Ser Lys Val Asp Ala Lys Gln Pro Gly 20 25 30Asp Tyr Phe Thr Thr
Ile Thr Ser Asp Glu His Pro Gly Lys Trp Arg 35 40 45Val Val Phe Phe
Trp Pro Lys Asp Phe Thr Phe Val Cys Pro Thr Glu 50 55 60Ile Ala Ala
Phe Ser Lys Leu Asn Asp Glu Phe Glu Asp Arg Asp Ala65 70 75 80Gln
Ile Leu Gly Val Ser Ile Asp Ser Glu Phe Ala His Phe Gln Trp 85 90
95Arg Ala Gln His Asn Asp Leu Lys Thr Leu Pro Phe Pro Met Leu Ser
100 105 110Asp Ile Lys Arg Glu Leu Ser Gln Ala Ala Gly Val Leu Asn
Ala Asp 115 120 125Gly Val Ala Asp Arg Val Thr Phe Ile Val Asp Pro
Asn Asn Glu Ile 130 135 140Gln Phe Val Ser Ala Thr Ala Gly Ser Val
Gly Arg Asn Val Asp Glu145 150 155 160Val Leu Arg Val Leu Asp Ala
Leu Gln Ser Asp Glu Leu Cys Ala Cys 165 170 175Asn Trp Arg Lys Gly
Asp Pro Thr Leu Asp Ala Gly Glu Leu Leu Lys 180 185 190Ala Ser Ala
19527272PRTMycobacterium tuberculosis 27Met Ser Gly Arg Gly Glu Pro
Thr Met Lys Thr Ile Ile Val Gly Ile1 5 10 15Asp Gly Ser His Ala Ala
Ile Thr Ala Ala Leu Trp Gly Val Asp Glu 20 25 30Ala Ile Ser Arg Ala
Val Pro Leu Arg Leu Val Ser Val Ile Lys Pro 35 40 45Thr His Pro Ser
Pro Asp Asp Tyr Asp Arg Asp Leu Ala His Ala Glu 50 55 60Arg Ser Leu
Arg Glu Ala Gln Ser Ala Val Glu Ala Ala Gly Lys Leu65 70 75 80Val
Lys Ile Glu Thr Asp Ile Pro Arg Gly Pro Ala Gly Pro Val Leu 85 90
95Val Glu Ala Ser Arg Asp Ala Glu Met Ile Cys Val Gly Ser Val Gly
100 105 110Ile Gly Arg Tyr Ala Ser Ser Ile Leu Gly Ser Thr Ala Thr
Glu Leu 115 120 125Ala Glu Lys Ala His Cys Pro Val Ala Val Met Arg
Ser Lys Val Asp 130 135 140Gln Pro Ala Ser Asp Ile Asn Trp Ile Val
Val Arg Met Thr Asp Ala145 150 155 160Pro Asp Asn Glu Ala Val Leu
Glu Tyr Ala Ala Arg Glu Ala Lys Leu 165 170 175Arg Gln Ala Pro Ile
Leu Ala Leu Gly Gly Arg Pro Glu Glu Leu Arg 180 185 190Glu Ile Pro
Asp Gly Glu Phe Glu Arg Arg Val Gln Asp Trp His His 195 200 205Arg
His Pro Asp Val Arg Val Tyr Pro Ile Thr Thr His Thr Gly Ile 210 215
220Ala Arg Phe Leu Ala Asp His Asp Glu Arg Val Gln Leu Ala Val
Ile225 230 235 240Gly Gly Gly Glu Ala Gly Gln Leu Ala Arg Leu Val
Gly Pro Ser Gly 245 250 255His Pro Val Phe Arg His Ala Glu Cys Ser
Val Leu Val Val Arg Arg 260 265 27028393PRTMycobacterium
tuberculosis 28Met Arg Asp Ala Ile Pro Leu Gly Arg Ile Ala Gly Phe
Val Val Asn1 5 10 15Val His Trp Ser Val Leu Val Ile Leu Trp Leu Phe
Thr Trp Ser Leu 20 25 30Ala Thr Met Leu Pro Gly Thr Val Gly Gly Tyr
Pro Ala Val Val Tyr 35 40 45Trp Leu Leu Gly Ala Gly Gly Ala Val Met
Leu Leu Ala Ser Leu Leu 50 55 60Ala His Glu Leu Ala His Ala Val Val
Ala Arg Arg Ala Gly Val Ser65 70 75 80Val Glu Ser Val Thr Leu Trp
Leu Phe Gly Gly Val Thr Ala Leu Gly 85 90 95Gly Glu Ala Lys Thr Pro
Lys Ala Ala Phe Arg Ile Ala Phe Ala Gly 100 105 110Pro Ala Thr Ser
Leu Ala Leu Ser Ala Thr Phe Gly Ala Leu Ala Ile 115 120 125Thr Leu
Ala Gly Val Arg Thr Pro Ala Ile Val Ile Ser Val Ala Trp 130 135
140Trp Leu Ala Thr Val Asn Leu Leu Leu Gly Leu Phe Asn Leu Leu
Pro145 150 155 160Gly Ala Pro Leu Asp Gly Gly Arg Leu Val Arg Ala
Tyr Leu Trp Arg 165 170 175Arg His Gly Asp Ser Val Arg Ala Gly Ile
Gly Ala Ala Arg Ala Gly 180 185 190Arg Val Val Ala Leu Val Leu Ile
Ala Leu Gly Leu Ala Glu Phe Val 195 200 205Ala Gly Gly Leu Val Gly
Gly Val Trp Leu Ala Phe Ile Gly Trp Phe 210 215 220Ile Phe Ala Ala
Ala Arg Glu Glu Glu Thr Arg Ile Ser Thr Gln Gln225 230 235 240Leu
Phe Ala Gly Val Arg Val Ala Asp Ala Met Thr Ala Gln Pro His 245 250
255Thr Ala Pro Gly Trp Ile Asn Val Glu Asp Phe Ile Gln Arg Tyr Val
260 265 270Leu Gly Glu Arg His Ser Ala Tyr Pro Val Ala Asp Arg Asp
Gly Ser 275 280 285Ile Thr Gly Leu Val Ala Leu Arg Gln Leu Arg Asp
Val Ala Pro Ser 290 295 300Arg Arg Ser Thr Thr Ser Val Gly Asp Ile
Ala Leu Pro Leu His Ser305 310 315 320Val Pro Thr Ala Arg Pro Gln
Glu Pro Leu Thr Ala Leu Leu Glu Arg 325 330 335Met Ala Pro Leu Gly
Pro Arg Ser Arg Ala Leu Val Thr Glu Gly Ser 340 345 350Ala Val Val
Gly Ile Val Thr Pro Ser Asp Val Ala Arg Leu Ile Asp 355 360 365Val
Tyr Arg Leu Ala Gln Pro Glu Pro Thr Phe Thr Thr Ser Pro Gln 370 375
380Asp Ala Asp Arg Phe Ser Asp Ala Gly385 39029413PRTMycobacterium
tuberculosis 29Met Ala Ser Ser Ala Ser Asp Gly Thr His Glu Arg Ser
Ala Phe Arg1 5 10 15Leu Ser Pro Pro Val Leu Ser Gly Ala Met Gly Pro
Phe Met His Thr 20 25 30Gly Leu Tyr Val Ala Gln Ser Trp Arg Asp Tyr
Leu Gly Gln Gln Pro 35 40 45Asp Lys Leu Pro Ile Ala Arg Pro Thr Ile
Ala Leu Ala Ala Gln Ala 50 55 60Phe Arg Asp Glu Ile Val Leu Leu Gly
Leu Lys Ala Arg Arg Pro Val65 70 75 80Ser Asn His Arg Val Phe Glu
Arg Ile Ser Gln Glu Val Ala Ala Gly 85 90 95Leu Glu Phe Tyr Gly Asn
Arg Arg Trp Leu Glu Lys Pro Ser Gly Phe 100 105 110Phe Ala Gln Pro
Pro Pro Leu Thr Glu Val Ala Val Arg Lys Val Lys 115 120 125Asp Arg
Arg Arg Ser Phe Tyr Arg Ile Phe Phe Asp Ser Gly Phe Thr 130 135
140Pro His Pro Gly Glu Pro Gly Ser Gln Arg Trp Leu Ser Tyr Thr
Ala145 150 155 160Asn Asn Arg Glu Tyr Ala Leu Leu Leu Arg His Pro
Glu Pro Arg Pro 165 170 175Trp Leu Val Cys Val His Gly Thr Glu Met
Gly Arg Ala Pro Leu Asp 180 185 190Leu Ala Val Phe Arg Ala Trp Lys
Leu His Asp Glu Leu Gly Leu Asn 195 200 205Ile Val Met Pro Val Leu
Pro Met His Gly Pro Arg Gly Gln Gly Leu 210 215 220Pro Lys Gly Ala
Val Phe Pro Gly Glu Asp Val Leu Asp Asp Val His225 230 235 240Gly
Thr Ala Gln Ala Val Trp Asp Ile Arg Arg Leu Leu Ser Trp Ile 245 250
255Arg Ser Gln Glu Glu Glu Ser Leu Ile Gly Leu Asn Gly Leu Ser Leu
260 265 270Gly Gly Tyr Ile Ala Ser Leu Val Ala Ser Leu Glu Glu Gly
Leu Ala 275 280 285Cys Ala Ile Leu Gly Val Pro Val Ala Asp Leu Ile
Glu Leu Leu Gly 290 295 300Arg His Cys Gly Leu Arg His Lys Asp Pro
Arg Arg His Thr Val Lys305 310 315 320Met Ala Glu Pro Ile Gly Arg
Met Ile Ser Pro Leu Ser Leu Thr Pro 325 330 335Leu Val Pro Met Pro
Gly Arg Phe Ile Tyr Ala Gly Ile Ala Asp Arg 340 345 350Leu Val His
Pro Arg Glu Gln Val Thr Arg Leu Trp Glu His Trp Gly 355 360 365Lys
Pro Glu Ile Val Trp Tyr Pro Gly Gly His Thr Gly Phe Phe Gln 370 375
380Ser Arg Pro Val Arg Arg Phe Val Gln Ala Ala Leu Glu Gln Ser
Gly385 390 395 400Leu Leu Asp Ala Pro Arg Thr Gln Arg Asp Arg Ser
Ala 405 41030120PRTMycobacterium tuberculosis 30Met Ser Thr Gln Arg
Pro Arg His Ser Gly Ile Arg Ala Val Gly Pro1 5 10 15Tyr Ala Trp Ala
Gly Arg Cys Gly Arg Ile Gly Arg Trp Gly Val His 20 25 30Gln Glu Ala
Met Met Asn Leu Ala Ile Trp His Pro Arg Lys Val Gln 35 40 45Ser Ala
Thr Ile Tyr Gln Val Thr Asp Arg Ser His Asp Gly Arg Thr 50 55 60Ala
Arg Val Pro Gly Asp Glu Ile Thr Ser Thr Val Ser Gly Trp Leu65 70 75
80Ser Glu Leu Gly Thr Gln Ser Pro Leu Ala Asp Glu Leu Ala Arg Ala
85 90 95Val Arg Ile Gly Asp Trp Pro Ala Ala Tyr Ala Ile Gly Glu His
Leu 100 105 110Ser Val Glu Ile Ala Val Ala Val 115
12031374PRTMycobacterium tuberculosis 31Met Arg Ser Glu Arg Leu Arg
Trp Leu Val Ala Ala Glu Gly Pro Phe1 5 10 15Ala Ser Val Tyr Phe Asp
Asp Ser His Asp Thr Leu Asp Ala Val Glu 20 25 30Arg Arg Glu Ala Thr
Trp Arg Asp Val Arg Lys His Leu Glu Ser Arg 35 40 45Asp Ala Lys Gln
Glu Leu Ile Asp Ser Leu Glu Glu Ala Val Arg Asp 50 55 60Ser Arg Pro
Ala Val Gly Gln Arg Gly Arg Ala Leu Ile Ala Thr Gly65 70 75 80Glu
Gln Val Leu Val Asn Glu His Leu Ile Gly Pro Pro Pro Ala Thr 85 90
95Val Ile Arg Leu Ser Asp Tyr Pro Tyr Val Val Pro Leu Ile Asp Leu
100 105 110Glu Met Arg Arg Pro Thr Tyr Val Phe Ala Ala Val Asp His
Thr Gly 115 120 125Ala Asp Val Lys Leu Tyr Gln Gly Ala Thr Ile Ser
Ser Thr Lys Ile 130 135 140Asp Gly Val Gly Tyr Pro Val His Lys Pro
Val Thr Ala Gly Trp Asn145 150 155 160Gly Tyr Gly Asp Phe Gln His
Thr Thr Glu Glu Ala Ile Arg Met Asn 165 170 175Cys Arg Ala Val Ala
Asp His Leu Thr Arg Leu Val Asp Ala Ala Asp 180 185 190Pro Glu Val
Val Phe Val Ser Gly Glu Val Arg Ser Arg Thr Asp Leu 195 200 205Leu
Ser Thr Leu Pro Gln Arg Val Ala Val Arg Val Ser Gln Leu His 210 215
220Ala Gly Pro Arg Lys Ser Ala Leu Asp Glu Glu Glu Ile Trp Asp
Leu225 230 235 240Thr Ser Ala Glu Phe Thr Arg Arg Arg Tyr Ala Glu
Ile Thr Asn Val 245 250 255Ala Gln Gln Phe Glu Ala Glu Ile Gly Arg
Gly Ser Gly Leu Ala Ala 260 265 270Gln Gly Leu Ala Glu Val Cys Ala
Ala Leu Arg Asp Gly Asp Val Asp 275 280 285Thr Leu Ile Val Gly Glu
Leu Gly Glu Ala Thr Val Val Thr Gly Lys 290 295 300Ala Arg Thr Thr
Val Ala Arg Asp Ala Asp Met Leu Ser Glu Leu Gly305 310 315 320Glu
Pro Val Asp Arg Val Ala Arg Ala Asp Glu Ala Leu Pro Phe Ala 325 330
335Ala Ile Ala Val Gly Ala Ala Leu Val Arg Asp Asp Asn Arg Ile Ala
340 345 350Pro Leu Asp Gly Val Gly Ala Leu Leu Arg Tyr Ala Ala Thr
Asn Arg 355 360 365Leu Gly Ser His Arg Ser 37032179PRTMycobacterium
tuberculosis 32Met Leu His Arg Asp Asp His Ile Asn Pro Pro Arg Pro
Arg Gly Leu1 5 10 15Asp Val Pro Cys Ala Arg Leu Arg Ala Thr Asn
Pro Leu Arg Ala Leu 20 25 30Ala Arg Cys Val Gln Ala Gly Lys Pro Gly
Thr Ser Ser Gly His Arg 35 40 45Ser Val Pro His Thr Ala Asp Leu Arg
Ile Glu Ala Trp Ala Pro Thr 50 55 60Arg Asp Gly Cys Ile Arg Gln Ala
Val Leu Gly Thr Val Glu Ser Phe65 70 75 80Leu Asp Leu Glu Ser Ala
His Ala Val His Thr Arg Leu Arg Arg Leu 85 90 95Thr Ala Asp Arg Asp
Asp Asp Leu Leu Val Ala Val Leu Glu Glu Val 100 105 110Ile Tyr Leu
Leu Asp Thr Val Gly Glu Thr Pro Val Asp Leu Arg Leu 115 120 125Arg
Asp Val Asp Gly Gly Val Asp Val Thr Phe Ala Thr Thr Asp Ala 130 135
140Ser Thr Leu Val Gln Val Gly Ala Val Pro Lys Ala Val Ser Leu
Asn145 150 155 160Glu Leu Arg Phe Ser Gln Gly Arg His Gly Trp Arg
Cys Ala Val Thr 165 170 175Leu Asp Val33375PRTMycobacterium
tuberculosis 33Val Thr Gln Thr Gly Lys Arg Gln Arg Arg Lys Phe Gly
Arg Ile Arg1 5 10 15Gln Phe Asn Ser Gly Arg Trp Gln Ala Ser Tyr Thr
Gly Pro Asp Gly 20 25 30Arg Val Tyr Ile Ala Pro Lys Thr Phe Asn Ala
Lys Ile Asp Ala Glu 35 40 45Ala Trp Leu Thr Asp Arg Arg Arg Glu Ile
Asp Arg Gln Leu Trp Ser 50 55 60Pro Ala Ser Gly Gln Glu Asp Arg Pro
Gly Ala Pro Phe Gly Glu Tyr65 70 75 80Ala Glu Gly Trp Leu Lys Gln
Arg Gly Ile Lys Asp Arg Thr Arg Ala 85 90 95His Tyr Arg Lys Leu Leu
Asp Asn His Ile Leu Ala Thr Phe Ala Asp 100 105 110Thr Asp Leu Arg
Asp Ile Thr Pro Ala Ala Val Arg Arg Trp Tyr Ala 115 120 125Thr Thr
Ala Val Gly Thr Pro Thr Met Arg Ala His Ser Tyr Ser Leu 130 135
140Leu Arg Ala Ile Met Gln Thr Ala Leu Ala Asp Asp Leu Ile Asp
Ser145 150 155 160Asn Pro Cys Arg Ile Ser Gly Ala Ser Thr Ala Arg
Arg Val His Lys 165 170 175Ile Arg Pro Ala Thr Leu Asp Glu Leu Glu
Thr Ile Thr Lys Ala Met 180 185 190Pro Asp Pro Tyr Gln Ala Phe Val
Leu Met Ala Ala Trp Leu Ala Met 195 200 205Arg Tyr Gly Glu Leu Thr
Glu Leu Arg Arg Lys Asp Ile Asp Leu His 210 215 220Gly Glu Val Ala
Arg Val Arg Arg Ala Val Val Arg Val Gly Glu Gly225 230 235 240Phe
Lys Val Thr Thr Pro Lys Ser Asp Ala Gly Val Arg Asp Ile Ser 245 250
255Ile Pro Pro His Leu Ile Pro Ala Ile Glu Asp His Leu His Lys His
260 265 270Val Asn Pro Gly Arg Glu Ser Leu Leu Phe Pro Ser Val Asn
Asp Pro 275 280 285Asn Arg His Leu Ala Pro Ser Ala Leu Tyr Arg Met
Phe Tyr Lys Ala 290 295 300Arg Lys Ala Ala Gly Arg Pro Asp Leu Arg
Val His Asp Leu Arg His305 310 315 320Ser Gly Ala Val Leu Ala Ala
Ser Thr Gly Ala Thr Leu Ala Glu Leu 325 330 335Met Gln Arg Leu Gly
His Ser Thr Ala Gly Ala Ala Leu Arg Tyr Gln 340 345 350His Ala Ala
Lys Gly Arg Asp Arg Glu Ile Ala Ala Leu Leu Ser Lys 355 360 365Leu
Ala Glu Asn Gln Glu Met 370 37534371PRTMycobacterium tuberculosis
34Met Arg Val Gly Ile Pro Thr Glu Thr Lys Asn Asn Glu Phe Arg Val1
5 10 15Ala Ile Thr Pro Ala Gly Val Ala Glu Leu Thr Arg Arg Gly His
Glu 20 25 30Val Leu Ile Gln Ala Gly Ala Gly Glu Gly Ser Ala Ile Thr
Asp Ala 35 40 45Asp Phe Lys Ala Ala Gly Ala Gln Leu Val Gly Thr Ala
Asp Gln Val 50 55 60Trp Ala Asp Ala Asp Leu Leu Leu Lys Val Lys Glu
Pro Ile Ala Ala65 70 75 80Glu Tyr Gly Arg Leu Arg His Gly Gln Ile
Leu Phe Thr Phe Leu His 85 90 95Leu Ala Ala Ser Arg Ala Cys Thr Asp
Ala Leu Leu Asp Ser Gly Thr 100 105 110Thr Ser Ile Ala Tyr Glu Thr
Val Gln Thr Ala Asp Gly Ala Leu Pro 115 120 125Leu Leu Ala Pro Met
Ser Glu Val Ala Gly Arg Leu Ala Ala Gln Val 130 135 140Gly Ala Tyr
His Leu Met Arg Thr Gln Gly Gly Arg Gly Val Leu Met145 150 155
160Gly Gly Val Pro Gly Val Glu Pro Ala Asp Val Val Val Ile Gly Ala
165 170 175Gly Thr Ala Gly Tyr Asn Ala Ala Arg Ile Ala Asn Gly Met
Gly Ala 180 185 190Thr Val Thr Val Leu Asp Ile Asn Ile Asp Lys Leu
Arg Gln Leu Asp 195 200 205Ala Glu Phe Cys Gly Arg Ile His Thr Arg
Tyr Ser Ser Ala Tyr Glu 210 215 220Leu Glu Gly Ala Val Lys Arg Ala
Asp Leu Val Ile Gly Ala Val Leu225 230 235 240Val Pro Gly Ala Lys
Ala Pro Lys Leu Val Ser Asn Ser Leu Val Ala 245 250 255His Met Lys
Pro Gly Ala Val Leu Val Asp Ile Ala Ile Asp Gln Gly 260 265 270Gly
Cys Phe Glu Gly Ser Arg Pro Thr Thr Tyr Asp His Pro Thr Phe 275 280
285Ala Val His Asp Thr Leu Phe Tyr Cys Val Ala Asn Met Pro Ala Ser
290 295 300Val Pro Lys Thr Ser Thr Tyr Ala Leu Thr Asn Ala Thr Met
Pro Tyr305 310 315 320Val Leu Glu Leu Ala Asp His Gly Trp Arg Ala
Ala Cys Arg Ser Asn 325 330 335Pro Ala Leu Ala Lys Gly Leu Ser Thr
His Glu Gly Ala Leu Leu Ser 340 345 350Glu Arg Val Ala Thr Asp Leu
Gly Val Pro Phe Thr Glu Pro Ala Ser 355 360 365Val Leu Ala
37035104PRTMycobacterium tuberculosis 35Met Val Ile Arg Phe Asp Gln
Ile Gly Ser Leu Val Leu Ser Met Lys1 5 10 15Ser Leu Ala Ser Leu Ser
Phe Gln Arg Cys Leu Arg Glu Asn Ser Ser 20 25 30Leu Val Ala Ala Leu
Asp Arg Leu Asp Ala Ala Val Asp Glu Leu Ser 35 40 45Ala Leu Ser Phe
Asp Ala Leu Thr Thr Pro Glu Arg Asp Arg Ala Arg 50 55 60Arg Asp Arg
Asp His His Pro Trp Ser Arg Ser Arg Ser Gln Leu Ser65 70 75 80Pro
Arg Met Ala His Gly Ala Val His Gln Cys Gln Trp Pro Lys Ala 85 90
95Val Trp Ala Val Ile Asp Asn Pro 10036344PRTMycobacterium
tuberculosis 36Val Leu Lys Asn Ala Val Leu Leu Ala Cys Arg Ala Pro
Ser Val His1 5 10 15Asn Ser Gln Pro Trp Arg Trp Val Ala Glu Ser Gly
Ser Glu His Thr 20 25 30Thr Val His Leu Phe Val Asn Arg His Arg Thr
Val Pro Ala Thr Asp 35 40 45His Ser Gly Arg Gln Ala Ile Ile Ser Cys
Gly Ala Val Leu Asp His 50 55 60Leu Arg Ile Ala Met Thr Ala Ala His
Trp Gln Ala Asn Ile Thr Arg65 70 75 80Phe Pro Gln Pro Asn Gln Pro
Asp Gln Leu Ala Thr Val Glu Phe Ser 85 90 95Pro Ile Asp His Val Thr
Ala Gly Gln Arg Asn Arg Ala Gln Ala Ile 100 105 110Leu Gln Arg Arg
Thr Asp Arg Leu Pro Phe Asp Ser Pro Met Tyr Trp 115 120 125His Leu
Phe Glu Pro Ala Leu Arg Asp Ala Val Asp Lys Asp Val Ala 130 135
140Met Leu Asp Val Val Ser Asp Asp Gln Arg Thr Arg Leu Val Val
Ala145 150 155 160Ser Gln Leu Ser Glu Val Leu Arg Arg Asp Asp Pro
Tyr Tyr His Ala 165 170 175Glu Leu Glu Trp Trp Thr Ser Pro Phe Val
Leu Ala His Gly Val Pro 180 185 190Pro Asp Thr Leu Ala Ser Asp Ala
Glu Arg Leu Arg Val Asp Leu Gly 195 200 205Arg Asp Phe Pro Val Arg
Ser Tyr Gln Asn Arg Arg Ala Glu Leu Ala 210 215 220Asp Asp Arg Ser
Lys Val Leu Val Leu Ser Thr Pro Ser Asp Thr Arg225 230 235 240Ala
Asp Ala Leu Arg Cys Gly Glu Val Leu Ser Thr Ile Leu Leu Glu 245 250
255Cys Thr Met Ala Gly Met Ala Thr Cys Thr Leu Thr His Leu Ile Glu
260 265 270Ser Ser Asp Ser Arg Asp Ile Val Arg Gly Leu Thr Arg Gln
Arg Gly 275 280 285Glu Pro Gln Ala Leu Ile Arg Val Gly Ile Ala Pro
Pro Leu Ala Ala 290 295 300Val Pro Ala Pro Thr Pro Arg Arg Pro Leu
Asp Ser Val Leu Gln Ile305 310 315 320Arg Gln Thr Pro Glu Lys Gly
Arg Asn Ala Ser Asp Arg Asn Ala Arg 325 330 335Glu Thr Gly Trp Phe
Ser Pro Pro 34037336PRTMycobacterium tuberculosis 37Val Trp Ser Ala
Ser Gly Gly Gln Cys Gly Lys Tyr Leu Ala Ala Ser1 5 10 15Met Val Leu
Gln Leu Asp Gly Leu Glu Arg His Gly Val Leu Glu Phe 20 25 30Gly Arg
Asp Arg Tyr Gly Pro Glu Val Arg Glu Glu Leu Leu Ala Met 35 40 45Ser
Ala Ala Ser Ile Asp Arg Tyr Leu Lys Thr Ala Lys Ala Lys Asp 50 55
60Gln Ile Ser Gly Val Ser Thr Thr Lys Pro Ser Pro Leu Leu Arg Asn65
70 75 80Ser Ile Lys Val Arg Arg Ala Gly Asp Glu Val Glu Ala Glu Pro
Gly 85 90 95Phe Phe Glu Gly Asp Thr Val Ala His Cys Gly Pro Thr Leu
Lys Gly 100 105 110Glu Phe Ala His Thr Leu Asn Leu Thr Asp Val His
Ile Gly Trp Val 115 120 125Phe Thr Arg Thr Val Arg Asn Asn Ala Arg
Thr His Ile Leu Ala Gly 130 135 140Leu Lys Ala Ser Val Thr Glu Ile
Pro His Gly Ile Thr Gly Leu Asp145 150 155 160Phe Asp Asn Gly Thr
Val Phe Leu Asn Lys Pro Val Ile Ser Trp Ala 165 170 175Gly Asp Asn
Gly Ile Tyr Phe Thr Arg Phe Arg Pro Tyr Lys Lys Asn 180 185 190His
Ala Thr Ile Glu Ser Lys Asn Asn His Leu Val Arg Lys Tyr Ala 195 200
205Phe Tyr Tyr Arg Tyr Asp Thr Ala Glu Glu Arg Ala Val Leu Asn Arg
210 215 220Met Trp Lys Leu Val Asn Asp Arg Leu Asn Tyr Leu Thr Pro
Thr Ile225 230 235 240Lys Pro Ile Gly Tyr Ala Ser Ser Ala Asp Gly
Arg Arg Arg Arg Leu 245 250 255Tyr Asp Ala Pro Gln Thr Pro Leu Asp
Arg Pro Leu Ala Ala Arg Val 260 265 270Leu Ser Ala Ala Gln Gln Ala
Asp Leu Ile Thr Tyr Arg Asp Ser Leu 275 280 285Asn Pro Ala Gln Ile
Gly Arg Lys Ile Ala Asp Leu Gln Asn Arg Leu 290 295 300Leu Ile Leu
Ala Lys Glu Lys Thr Glu Gln Leu Tyr Leu Ala Asn Ile305 310 315
320Pro Thr Ala Leu Pro Asp Ile His Lys Gly Ile Leu Ile Lys Ala Gly
325 330 33538110PRTMycobacterium tuberculosis 38Val Val Gln Gly Arg
Thr Val Leu Phe Arg Thr Ala Glu Gly Ala Lys1 5 10 15Leu Phe Ser Ala
Val Ala Lys Cys Ala Val Ala Phe Glu Ala Asp Asp 20 25 30His Asn Val
Ala Glu Gly Trp Ser Val Ile Val Lys Val Arg Ala Gln 35 40 45Val Leu
Thr Thr Asp Ala Gly Val Arg Glu Ala Glu Arg Ala Gln Leu 50 55 60Leu
Pro Trp Thr Ala Thr Leu Lys Arg His Cys Val Arg Val Ile Pro65 70 75
80Trp Glu Ile Thr Gly Arg His Phe Arg Phe Gly Pro Glu Pro Asp Arg
85 90 95Ser Gln Thr Phe Ala Cys Glu Ala Ser Ser His Asn Gln Arg 100
105 11039463PRTMycobacterium tuberculosis 39Met Asn His Leu Thr Thr
Leu Asp Ala Gly Phe Leu Lys Ala Glu Asp1 5 10 15Val Asp Arg His Val
Ser Leu Ala Ile Gly Ala Leu Ala Val Ile Glu 20 25 30Gly Pro Ala Pro
Asp Gln Glu Ala Phe Leu Ser Ser Leu Ala Gln Arg 35 40 45Leu Arg Pro
Cys Thr Arg Phe Gly Gln Arg Leu Arg Leu Arg Pro Phe 50 55 60Asp Leu
Gly Ala Pro Lys Trp Val Asp Asp Pro Asp Phe Asp Leu Gly65 70 75
80Arg His Val Trp Arg Ile Ala Leu Pro Arg Pro Gly Asn Glu Asp Gln
85 90 95Leu Phe Glu Leu Ile Ala Asp Leu Met Ala Arg Arg Leu Asp Arg
Gly 100 105 110Arg Pro Leu Trp Glu Val Trp Val Ile Glu Gly Leu Ala
Asp Ser Lys 115 120 125Trp Ala Ile Leu Thr Lys Leu His His Cys Met
Ala Asp Gly Ile Ala 130 135 140Ala Thr His Leu Leu Ala Gly Leu Ser
Asp Glu Ser Met Ser Asp Ser145 150 155 160Phe Ala Ser Asn Ile His
Thr Thr Met Gln Ser Gln Ser Ala Ser Val 165 170 175Arg Arg Gly Gly
Phe Arg Val Asn Pro Ser Glu Ala Leu Thr Ala Ser 180 185 190Thr Ala
Val Met Ala Gly Ile Val Arg Ala Ala Lys Gly Ala Ser Glu 195 200
205Ile Ala Ala Gly Val Leu Ser Pro Ala Ala Ser Ser Leu Asn Gly Pro
210 215 220Ile Ser Asp Leu Arg Arg Tyr Ser Ala Ala Lys Val Pro Leu
Ala Asp225 230 235 240Val Glu Gln Val Cys Arg Lys Phe Asp Val Thr
Ile Asn Asp Val Ala 245 250 255Leu Ala Ala Ile Thr Glu Ser Tyr Arg
Asn Val Leu Ile Gln Arg Gly 260 265 270Glu Arg Pro Arg Phe Asp Ser
Leu Arg Thr Leu Val Pro Val Ser Thr 275 280 285Arg Ser Asn Ser Ala
Leu Ser Lys Thr Asp Asn Arg Val Ser Leu Met 290 295 300Leu Pro Asn
Leu Pro Val Asp Gln Glu Asn Pro Leu Gln Arg Leu Arg305 310 315
320Ile Val His Ser Arg Leu Thr Arg Ala Lys Ala Gly Gly Gln Arg Gln
325 330 335Phe Gly Asn Thr Leu Met Ala Ile Ala Asn Arg Leu Pro Phe
Pro Met 340 345 350Thr Ala Trp Ala Val Gly Leu Leu Met Arg Leu Pro
Gln Arg Gly Val 355 360 365Val Thr Val Ala Thr Asn Val Pro Gly Pro
Arg Arg Pro Leu Gln Ile 370 375 380Met Gly Arg Arg Val Leu Asp Leu
Tyr Pro Val Ser Pro Ile Ala Met385 390 395 400Gln Leu Arg Thr Ser
Val Ala Met Leu Ser Tyr Ala Asp Asp Leu Tyr 405 410 415Phe Gly Ile
Leu Ala Asp Tyr Asp Val Val Ala Asp Ala Gly Gln Leu 420 425 430Ala
Arg Gly Ile Glu Asp Ala Val Ala Arg Leu Val Ala Ile Ser Lys 435 440
445Arg Arg Lys Val Thr Arg Arg Arg Gly Ala Leu Ser Leu Val Val 450
455 46040332PRTMycobacterium tuberculosis 40Met Asn Thr His Phe Pro
Asp Ala Glu Thr Val Arg Thr Val Leu Thr1 5 10 15Leu Ala Val Arg Ala
Pro Ser Ile His Asn Thr Gln Pro Trp Arg Trp 20 25 30Arg Val Cys Pro
Thr Ser Leu Glu Leu Phe Ser Arg Pro Asp Met Gln 35 40 45Leu Arg Ser
Thr Asp Pro Asp Gly Arg Glu Leu Ile Leu Ser Cys Gly 50 55 60Val Ala
Leu His His Cys Val Val Ala Leu Ala Ser Leu Gly Trp Gln65 70 75
80Ala Lys Val Asn Arg Phe Pro Asp Pro Lys Asp Arg Cys His Leu Ala
85 90 95Thr Ile Gly Val Gln Pro Leu Val Pro Asp Gln Ala Asp Val Ala
Leu 100 105 110Ala Ala Ala Ile Pro Arg Arg Arg Thr Asp Arg Arg Ala
Tyr Ser Cys 115 120 125Trp Pro Val Pro Gly Gly Asp Ile Ala Leu Met
Ala Ala Arg Ala Ala 130 135 140Arg Gly Gly Val Met Leu Arg Gln Val
Ser Ala Leu Asp Arg Met Lys145 150 155 160Ala Ile Val Ala Gln Ala
Val Leu Asp His Val Thr Asp Glu Glu Tyr 165 170 175Leu Arg Glu Leu
Thr Ile Trp
Ser Gly Arg Tyr Gly Ser Val Ala Gly 180 185 190Val Pro Ala Arg Asn
Glu Pro Pro Ser Asp Pro Ser Ala Pro Ile Pro 195 200 205Gly Arg Leu
Phe Ala Gly Pro Gly Leu Ser Gln Pro Ser Asp Val Leu 210 215 220Pro
Ala Asp Asp Gly Ala Ala Ile Leu Ala Leu Gly Thr Glu Thr Asp225 230
235 240Asp Arg Leu Ala Arg Leu Arg Ala Gly Glu Ala Ala Ser Ile Val
Leu 245 250 255Leu Thr Ala Thr Ala Met Gly Leu Ala Cys Cys Pro Ile
Thr Glu Pro 260 265 270Leu Glu Ile Ala Lys Thr Arg Asp Ala Val Arg
Ala Glu Val Phe Gly 275 280 285Ala Gly Gly Tyr Pro Gln Met Leu Leu
Arg Val Gly Trp Ala Pro Ile 290 295 300Asn Ala Asp Pro Leu Pro Pro
Thr Pro Arg Arg Glu Leu Ser Gln Val305 310 315 320Val Glu Trp Pro
Glu Glu Leu Leu Arg Gln Arg Cys 325 33041578PRTMycobacterium
tuberculosis 41Met Thr Thr Gly Gly Leu Val Asp Glu Asn Asp Gly Ala
Ala Met Arg1 5 10 15Pro Leu Arg His Thr Leu Ser Gln Leu Arg Leu His
Glu Leu Leu Val 20 25 30Glu Val Gln Asp Arg Val Glu Gln Ile Val Glu
Gly Arg Asp Arg Leu 35 40 45Asp Gly Leu Val Glu Ala Met Leu Val Val
Thr Ala Gly Leu Asp Leu 50 55 60Glu Ala Thr Leu Arg Ala Ile Val His
Ser Ala Thr Ser Leu Val Asp65 70 75 80Ala Arg Tyr Gly Ala Met Glu
Val His Asp Arg Gln His Arg Val Leu 85 90 95His Phe Val Tyr Glu Gly
Ile Asp Glu Glu Thr Val Arg Arg Ile Gly 100 105 110His Leu Pro Lys
Gly Leu Gly Val Ile Gly Leu Leu Ile Glu Asp Pro 115 120 125Lys Pro
Leu Arg Leu Asp Asp Val Ser Ala His Pro Ala Ser Ile Gly 130 135
140Phe Pro Pro Tyr His Pro Pro Met Arg Thr Phe Leu Gly Val Pro
Val145 150 155 160Arg Val Arg Asp Glu Ser Phe Gly Thr Leu Tyr Leu
Thr Asp Lys Thr 165 170 175Asn Gly Gln Pro Phe Ser Asp Asp Asp Glu
Val Leu Val Gln Ala Leu 180 185 190Ala Ala Ala Ala Gly Ile Ala Val
Ala Asn Ala Arg Leu Tyr Gln Gln 195 200 205Ala Lys Ala Arg Gln Ser
Trp Ile Glu Ala Thr Arg Asp Ile Ala Thr 210 215 220Glu Leu Leu Ser
Gly Thr Glu Pro Ala Thr Val Phe Arg Leu Val Ala225 230 235 240Ala
Glu Ala Leu Lys Leu Thr Ala Ala Asp Ala Ala Leu Val Ala Val 245 250
255Pro Val Asp Glu Asp Met Pro Ala Ala Asp Val Gly Glu Leu Leu Val
260 265 270Ile Glu Thr Val Gly Ser Ala Val Ala Ser Ile Val Gly Arg
Thr Ile 275 280 285Pro Val Ala Gly Ala Val Leu Arg Glu Val Phe Val
Asn Gly Ile Pro 290 295 300Arg Arg Val Asp Arg Val Asp Leu Glu Gly
Leu Asp Glu Leu Ala Asp305 310 315 320Ala Gly Pro Ala Leu Leu Leu
Pro Leu Arg Ala Arg Gly Thr Val Ala 325 330 335Gly Val Val Val Val
Leu Ser Gln Gly Gly Pro Gly Ala Phe Thr Asp 340 345 350Glu Gln Leu
Glu Met Met Ala Ala Phe Ala Asp Gln Ala Ala Leu Ala 355 360 365Trp
Gln Leu Ala Thr Ser Gln Arg Arg Met Arg Glu Leu Asp Val Leu 370 375
380Thr Asp Arg Asp Arg Ile Ala Arg Asp Leu His Asp His Val Ile
Gln385 390 395 400Arg Leu Phe Ala Ile Gly Leu Ala Leu Gln Gly Ala
Val Pro His Glu 405 410 415Arg Asn Pro Glu Val Gln Gln Arg Leu Ser
Asp Val Val Asp Asp Leu 420 425 430Gln Asp Val Ile Gln Glu Ile Arg
Thr Thr Ile Tyr Asp Leu His Gly 435 440 445Ala Ser Gln Gly Ile Thr
Arg Leu Arg Gln Arg Ile Asp Ala Ala Val 450 455 460Ala Gln Phe Ala
Asp Ser Gly Leu Arg Thr Ser Val Gln Phe Val Gly465 470 475 480Pro
Leu Ser Val Val Asp Ser Ala Leu Ala Asp Gln Ala Glu Ala Val 485 490
495Val Arg Glu Ala Val Ser Asn Ala Val Arg His Ala Lys Ala Ser Thr
500 505 510Leu Thr Val Arg Val Lys Val Asp Asp Asp Leu Cys Ile Glu
Val Thr 515 520 525Asp Asn Gly Arg Gly Leu Pro Asp Glu Phe Thr Gly
Ser Gly Leu Thr 530 535 540Asn Leu Arg Gln Arg Ala Glu Gln Ala Gly
Gly Glu Phe Thr Leu Ala545 550 555 560Ser Val Pro Gly Ala Ser Gly
Thr Val Leu Arg Trp Ser Ala Pro Leu 565 570 575Ser
Gln42268PRTMycobacterium tuberculosis 42Met Ser Asp Pro Arg Pro Ala
Arg Ala Val Val Val Gly Ile Asp Gly1 5 10 15Ser Arg Ala Ala Thr His
Ala Ala Leu Trp Ala Val Asp Glu Ala Val 20 25 30Asn Arg Asp Ile Pro
Leu Arg Leu Val Tyr Val Ile Asp Pro Ser Gln 35 40 45Leu Ser Ala Ala
Gly Glu Gly Gly Gly Gln Ser Ala Ala Arg Ala Ala 50 55 60Leu His Asp
Ala Ser Arg Lys Val Glu Ala Thr Gly Gln Pro Val Lys65 70 75 80Ile
Glu Thr Glu Val Leu Cys Gly Arg Pro Leu Thr Lys Leu Met Gln 85 90
95Glu Ser Arg Ser Ala Ala Met Leu Cys Val Gly Ser Val Gly Leu Asp
100 105 110His Val Arg Gly Arg Arg Gly Ser Val Ala Ala Thr Leu Ala
Gly Ser 115 120 125Ala Leu Cys Pro Val Ala Val Ile His Pro Ser Pro
Ala Glu Pro Ala 130 135 140Thr Thr Ser Gln Val Ser Ala Val Val Ala
Glu Val Asp Asn Gly Val145 150 155 160Val Leu Arg His Ala Phe Glu
Glu Ala Arg Leu Arg Gly Val Pro Leu 165 170 175Arg Ala Val Ala Val
His Ala Ala Glu Thr Pro Asp Asp Val Glu Gln 180 185 190Gly Ser Arg
Leu Ala His Val His Leu Ser Arg Arg Leu Ala His Trp 195 200 205Thr
Arg Leu Tyr Pro Glu Val Arg Val Asp Arg Ala Ile Ala Gly Gly 210 215
220Ser Ala Cys Arg His Leu Ala Ala Asn Ala Lys Pro Gly Gln Leu
Phe225 230 235 240Val Ala Asp Ser His Ser Ala His Glu Leu Cys Gly
Ala Tyr Gln Pro 245 250 255Gly Cys Ala Val Leu Thr Val Arg Ser Ala
Asn Leu 260 26543181PRTMycobacterium tuberculosis 43Met Thr Glu Tyr
Glu Gly Pro Lys Thr Lys Phe His Ala Leu Met Gln1 5 10 15Glu Gln Ile
His Asn Glu Phe Thr Ala Ala Gln Gln Tyr Val Ala Ile 20 25 30Ala Val
Tyr Phe Asp Ser Glu Asp Leu Pro Gln Leu Ala Lys His Phe 35 40 45Tyr
Ser Gln Ala Val Glu Glu Arg Asn His Ala Met Met Leu Val Gln 50 55
60His Leu Leu Asp Arg Asp Leu Arg Val Glu Ile Pro Gly Val Asp Thr65
70 75 80Val Arg Asn Gln Phe Asp Arg Pro Arg Glu Ala Leu Ala Leu Ala
Leu 85 90 95Asp Gln Glu Arg Thr Val Thr Asp Gln Val Gly Arg Leu Thr
Ala Val 100 105 110Ala Arg Asp Glu Gly Asp Phe Leu Gly Glu Gln Phe
Met Gln Trp Phe 115 120 125Leu Gln Glu Gln Ile Glu Glu Val Ala Leu
Met Ala Thr Leu Val Arg 130 135 140Val Ala Asp Arg Ala Gly Ala Asn
Leu Phe Glu Leu Glu Asn Phe Val145 150 155 160Ala Arg Glu Val Asp
Val Ala Pro Ala Ala Ser Gly Ala Pro His Ala 165 170 175Ala Gly Gly
Arg Leu 18044274PRTMycobacterium tuberculosis 44Met Thr Trp Ala Asp
Glu Val Leu Ala Gly His Pro Phe Val Val Ala1 5 10 15His Arg Gly Ala
Ser Ala Ala Arg Pro Glu His Thr Leu Ala Ala Tyr 20 25 30Asp Leu Ala
Leu Lys Glu Gly Ala Asp Gly Val Glu Cys Asp Val Arg 35 40 45Leu Thr
Arg Asp Gly His Leu Val Cys Val His Asp Arg Arg Leu Asp 50 55 60Arg
Thr Ser Thr Gly Ala Gly Leu Val Ser Thr Met Thr Leu Ala Gln65 70 75
80Leu Arg Glu Leu Glu Tyr Gly Ala Trp His Asp Ser Trp Arg Pro Asp
85 90 95Gly Ser His Gly Asp Thr Ser Leu Leu Thr Leu Asp Ala Leu Val
Ser 100 105 110Leu Val Leu Asp Trp His Arg Pro Val Lys Ile Phe Val
Glu Thr Lys 115 120 125His Pro Val Arg Tyr Gly Ser Leu Val Glu Asn
Lys Leu Leu Ala Leu 130 135 140Leu His Arg Phe Gly Ile Ala Ala Pro
Ala Ser Ala Asp Arg Ser Arg145 150 155 160Ala Val Val Met Ser Phe
Ser Ala Ala Ala Val Trp Arg Ile Arg Arg 165 170 175Ala Ala Pro Leu
Leu Pro Thr Val Leu Leu Gly Lys Thr Pro Arg Tyr 180 185 190Leu Thr
Ser Ser Ala Ala Thr Ala Val Gly Ala Thr Ala Val Gly Pro 195 200
205Ser Leu Pro Ala Leu Lys Glu Tyr Pro Gln Leu Val Asp Arg Ser Ala
210 215 220Ala Gln Gly Arg Ala Val Tyr Cys Trp Asn Val Asp Glu Tyr
Glu Asp225 230 235 240Ile Asp Phe Cys Arg Glu Val Gly Val Ala Trp
Ile Gly Thr His His 245 250 255Pro Gly Arg Thr Lys Ala Trp Leu Glu
Asp Gly Arg Ala Asn Gly Thr 260 265 270Thr Arg45248PRTMycobacterium
tuberculosis 45Val Ser Asp Gly Glu Gln Ala Lys Ser Arg Arg Arg Arg
Gly Arg Arg1 5 10 15Arg Gly Arg Arg Ala Ala Ala Thr Ala Glu Asn His
Met Asp Ala Gln 20 25 30Pro Ala Gly Asp Ala Thr Pro Thr Pro Ala Thr
Ala Lys Arg Ser Arg 35 40 45Ser Arg Ser Pro Arg Arg Gly Ser Thr Arg
Met Arg Thr Val His Glu 50 55 60Thr Ser Ala Gly Gly Leu Val Ile Asp
Gly Ile Asp Gly Pro Arg Asp65 70 75 80Ala Gln Val Ala Ala Leu Ile
Gly Arg Val Asp Arg Arg Gly Arg Leu 85 90 95Leu Trp Ser Leu Pro Lys
Gly His Ile Glu Leu Gly Glu Thr Ala Glu 100 105 110Gln Thr Ala Ile
Arg Glu Val Ala Glu Glu Thr Gly Ile Arg Gly Ser 115 120 125Val Leu
Ala Ala Leu Gly Arg Ile Asp Tyr Trp Phe Val Thr Asp Gly 130 135
140Arg Arg Val His Lys Thr Val His His Tyr Leu Met Arg Phe Leu
Gly145 150 155 160Gly Glu Leu Ser Asp Glu Asp Leu Glu Val Ala Glu
Val Ala Trp Val 165 170 175Pro Ile Arg Glu Leu Pro Ser Arg Leu Ala
Tyr Ala Asp Glu Arg Arg 180 185 190Leu Ala Glu Val Ala Asp Glu Leu
Ile Asp Lys Leu Gln Ser Asp Gly 195 200 205Pro Ala Ala Leu Pro Pro
Leu Pro Pro Ser Ser Pro Arg Arg Arg Pro 210 215 220Gln Thr His Ser
Arg Ala Arg His Ala Asp Asp Ser Ala Pro Gly Gln225 230 235 240His
Asn Gly Pro Gly Pro Gly Pro 24546819DNAMycobacterium tuberculosis
46gtggaaccga aacgcagtcg cctcgtcgta tgtgcacccg agccatcgca cgcgcgggaa
60ttcccggatg tcgccgtatt ctccggcggc cgggctaacg catcccaggc cgaacggttg
120gctcgtgccg tgggtcgcgt gttggccgat cggggcgtca ccgggggtgc
tcgggtgcgg 180ctgaccatgg cgaactgcgc cgatgggccg acgctggtgc
agataaacct gcaggtaggt 240gacaccccat taagggcgca ggccgccacc
gcgggcatcg atgatctgcg acccgcactg 300atcagactgg atcgacagat
cgtgcgggcg tcggcacagt ggtgcccccg gccttggccg 360gatcggcccc
gccggcgatt gaccacgccg gccgaggcgc tagtcacccg ccgcaaaccg
420gtcgtgctaa ggcgcgcaac cccgttgcag gcgattgccg ctatggacgc
catggactac 480gacgtgcatt tgttcaccga cgccgagacg ggggaggacg
ctgtggtcta tcgggctgga 540ccgtcggggc tgcggctggc ccgccagcac
cacgtatttc ccccaggatg gtcacgttgt 600cgcgccccag ccgggccgcc
ggtgccgctg attgtgaatt cgcgtccgac accggttctc 660acggaggccg
ccgcggtgga ccgggcgcgc gaacatggac tgccattcct gtttttcacc
720gaccaggcca ccggccgcgg ccagctgctc tactcccgct acgacggcaa
cctcgggttg 780atcaccccga ccggtgacgg cgttgccgac ggtctggca
81947819DNAMycobacterium tuberculosis 47gtggaaccga aacgcagtcg
cctcgtcgta tgtgcacccg agccatcgca cgcgcgggaa 60ttcccggatg tcgccgtatt
ctccggcggc cgggctaacg catcccaggc cgaacggttg 120gctcgtgccg
tgggtcgcgt gttggccgat cggggcgtca ccgggggtgc tcgggtgcgg
180ctgaccatgg cgaactgcgc cgatgggccg acgctggtgc agataaacct
gcaggtaggt 240gacaccccat taagggcgca ggccgccacc gcgggcatcg
atgatctgcg acccgcactg 300atcagactgg atcgacagat cgtgcgggcg
tcggcacagt ggtgcccccg gccttggccg 360gatcggcccc gccggcgatt
gaccacgccg gccgaggcgc tagtcacccg ccgcaaaccg 420gtcgtgctaa
ggcgcgcaac cccgttgcag gcgattgccg ctatggacgc catggactac
480gacgtgcatt tgttcaccga cgccgagacg ggggaggacg ctgtggtcta
tcgggctgga 540ccgtcggggc tgcggctggc ccgccagcac cacgtatttc
ccccaggatg gtcacgttgt 600cgcgccccag ccgggccgcc ggtgccgctg
attgtgaatt cgcgtccgac accggttctc 660acggaggccg ccgcggtgga
ccgggcgcgc gaacatggac tgccattcct gtttttcacc 720gaccaggcca
ccggccgcgg ccagctgctc tactcccgct acgacggcaa cctcgggttg
780atcaccccga ccggtgacgg cgttgccgac ggtctggca
81948342DNAMycobacterium tuberculosis 48gtggagtccg aaccgctgta
caagctcaag gcggagttct tcaaaaccct tgcgcatccg 60gcgcggatca ggattttgga
gctgctggtc gagcgggacc gttcggtcgg tgagttgctg 120tcctcggacg
tcggcctgga gtcgtcgaac ctgtcccagc agctgggtgt gctacgccgg
180gcgggtgttg tcgcggcacg tcgtgacggc aacgcgatga tctattcgat
tgccgcaccc 240gatatcgccg agctgctggc ggtggcacgc aaggtgctgg
ccagggtgct cagcgaccgg 300gtggcggtgc tagaggacct ccgcgccggc
ggctcggcca cg 342491032DNAMycobacterium tuberculosis 49atgcctatcg
caacgcccga ggtctacgcg gagatgctcg gtcaggccaa acaaaactcg 60tacgctttcc
cggctatcaa ctgcacctcc tcggaaaccg tcaacgccgc gatcaaaggt
120ttcgccgacg ccggcagtga cggaatcatc cagttctcga ccggtggcgc
agaattcggc 180tccggcctcg gggtcaaaga catggtgacc ggtgcggtcg
ccttggcgga gttcacccac 240gttatcgcgg ccaagtaccc ggtcaacgtg
gcgctgcaca ccgaccactg ccccaaggac 300aagttggaca gctatgtccg
gcccttgctg gcgatctcgg cgcaacgcgt gagcaaaggt 360ggcaatcctt
tgttccagtc gcacatgtgg gacggctcgg cagtgccaat cgatgagaac
420ctggccatcg cccaggagct gctcaaggcg gcggcggccg ccaagatcat
tctggagatc 480gagatcggcg tcgtcggcgg cgaagaggac ggcgtggcga
acgagatcaa cgagaagctg 540tacaccagcc cggaggactt cgagaaaacc
atcgaggcgc tgggcgccgg tgagcacggc 600aaatacctgc tggccgcgac
gttcggcaac gtgcatggcg tctacaagcc cggcaacgtc 660aagcttcgcc
ccgacatcct tgcgcaaggg caacaggtgg cggcggccaa gctcggactg
720ccggccgacg ccaagccgtt cgacttcgtg ttccacggcg gctcgggttc
gcttaagtcg 780gagatcgagg aggcgctgcg ctacggcgtg gtgaagatga
acgtcgacac cgacacccag 840tacgcgttca cccgcccgat cgccggtcac
atgttcacca actacgacgg agtgctcaag 900gtcgatggcg aggtgggtgt
caagaaggtc tacgacccgc gcagctacct caagaaggcc 960gaagcttcga
tgagccagcg ggtcgttcag gcgtgcaatg acctgcactg cgccggaaag
1020tccctaaccc ac 103250339DNAMycobacterium tuberculosis
50atgggtgagc acgccatcaa gcggcacatg cggcaacgga agcctacgaa gcatccccta
60gcccagaaac ggggcgcgcg gattctggtc ttcaccgacg atccccgcag gagcgtcctc
120atagtgcccg gttgccacct ggattccatg cgccgagaaa agaacgcgta
ctacttccag 180gacggcaatg cgttggttgg gatggttgtc tcgggcggca
cggttgagta cgacgccgac 240gaccgcacat atgtcgtgca gctcaccgac
ggaaggcaca ccactgagtc atctttcgaa 300cactcatcgc cgagtcgatc
acctcaatcc gatgaccta 339511140DNAMycobacterium tuberculosis
51gtggctggca atcctgatgt ggtgacggtg ctgctgggcg gtgacgtcat gctcggccgt
60ggcgtcgatc agatcctgcc tcatcccggc aaaccgcaat tgcgcgaacg gtatatgcgg
120gatgcgaccg gctatgttcg cctggccgag cgggtgaacg ggcgcattcc
gctccccgtg 180gattggcgct ggccctgggg cgaggcgttg gcggtccttg
agaacaccgc gaccgacgtc 240tgtttgatca atctggagac gacgatcacc
gccgacggtg aattcgccga ccgcaaaccg 300gtctgctacc ggatgcaccc
ggataacgtg ccggcgctga cggcattgcg gccgcacgtg 360tgcgcgctgg
ccaacaacca cattctcgat ttcggctacc aggggctgac cgatacggtc
420gcggctctcg ccggtgcggg gatccagagt gtcggggcgg gagccgattt
gctcgccgct 480cgccgctcgg cgctagtcac ggttggccat gaacgccggg
tgatcgtcgg ctcggtagcg 540gcggaatcca gcggcgtccc cgaatcctgg
gccgcccgcc gcgaccggcc cggagtgtgg 600ttgatccggg atccggcgca
acgcgacgtc gccgacgatg tggcggcaca ggtgctggcg 660gacaaacgcc
ccggcgatat cgccatagtc tcgatgcatt ggggatccaa ttggggctat
720gcgaccgcac ccggcgacgt cgcgttcgcg caccgactga tcgacgccgg
catcgacatg 780gtccacggac attcctcgca ccatccgcgg ccaatcgaga
tatatcgcgg taaaccgatc 840ctgtacggat gcggtgacgt cgttgacgac
tacgaaggca tcggcgggca
cgagtcgttc 900cgcagtgaac tgcgactgct gtatctgacc gtcaccgatc
ccgccagcgg gaacctgatc 960tcgctgcaga tgcttccact gcgagtgtcg
cggatgcgcc tacagcgtgc ctcccagacc 1020gacaccgaat ggctccgcaa
caccattgag cgcatcagcc gccggttcgg gattcgagtc 1080gtgactcgac
ccgacaacct gctggaggtc gttcccgctg ccaacctaac gagcaaggag
1140521191DNAMycobacterium tuberculosis 52gtgacagacc acgtgcgcga
ggcggacgac gcgaacatcg acgatctgtt gggcgacctg 60ggcggtaccg cgcgcgccga
gcgtgcgaag cttgtcgagt ggttgctcga gcagggcatc 120acccccgacg
agattcgggc gaccaacccg ccgttgctgc tggccacccg ccacctcgtc
180ggcgacgacg gcacctacgt atccgcaagg gagattagcg agaactatgg
cgttgacctc 240gagctgctgc agcgggtgca gcgcgctgtc ggtctggcca
gagtggatga tcctgacgcg 300gtggtgcaca tgcgtgccga cggtgaggcg
gccgcacgcg cacagcggtt cgttgagctg 360gggctgaatc ccgaccaagt
cgtgctggtc gtgcgtgtgc tcgccgaggg cttgtcacac 420gccgccgagg
ccatgcgcta caccgcgctg gaggccatta tgcggccggg ggctaccgag
480ttggacatcg cgaaggggtc gcaggcgctg gtgagccaga tcgtgccgct
gctggggccg 540atgatccagg acatgctgtt catgcagctg cggcacatga
tggagacgga ggccgtcaac 600gccggagagc gtgcggccgg caagccgcta
ccgggagcgc gacaggtcac cgttgccttc 660gccgacctgg tcggtttcac
ccagctaggc gaagtggtgt cggccgaaga gctagggcac 720ctcgccgggc
ggctggccgg cctcgcgcgt gacctgaccg ctccgccggt gtggttcatt
780aagacgatcg gcgacgcggt catgttggtc tgtcctgatc cggcgccatt
gctggacacc 840gtgctgaagc tggtcgaggt cgtcgacacc gacaacaact
ttccccggct gcgagccggc 900gtcgcctccg ggatggcggt tagccgggcc
ggcgactggt tcggcagccc ggtcaacgtg 960gcaagccggg tgaccggggt
ggcgcgcccg ggtgccgtgc tggtcgcgga ttcggtgcgg 1020gaggcccttg
gtgatgcccc cgaagccgac ggatttcagt ggtccttcgc cggcccccgt
1080cgcctcaggg gaatccgggg tgacgtcagg ctttttcgag tccggcgagg
ggccactcgc 1140accggctccg gcggcgcggc ccaagacgac gatttggccg
gctcgtcacc g 1191531338DNAMycobacterium tuberculosis 53atggtagagc
ccggcaattt ggcaggcgcg accggcgccg aatggatcgg ccggccaccg 60cacgaggaat
tgcagcgcaa agtgcgcccg ctgctgccat ccgacgatcc gttctacttc
120ccacctgccg gctaccagca tgccgtgccc ggaacggtgt tgcgctcgcg
cgatgtcgaa 180ctggcgttta tgggcttgat tccgcagccc gtcaccgcta
cccagctgct gtaccggacc 240acgaacatgt acggcaaccc cgaggcgacg
gtgaccacgg tgatcgtccc agcggagctt 300gccccgggtc agacctgccc
cttgctgtcg taccagtgtg cgatcgatgc catgtcgtcg 360cgctgttttc
cgtcatatgc cctgcgacga cgggccaagg ccctggggtc actgacccaa
420atggagctgt tgatgatcag cgccgcactt gccgaaggat gggcggtatc
agtacccgac 480catgaagggc cgaaagggct gtgggggtcg ccgtatgaac
ccggttaccg agtcctcgac 540ggaatccggg ctgccttgaa ttccgagcgt
gtcgggttgt ccccggcaac gccgatcggg 600ctgtggggct actccggcgg
cgggctggcc agcgcgtggg ccgccgaagc atgcggcgag 660tacgcaccgg
acctagacat cgtcggcgcc gtgctgggat cacccgtcgg tgaccttggt
720cacacgttcc gccggctcaa tggcactctt cttgccggtc tgcccgcgtt
ggtggtggcc 780gcgctgcaac acagctaccc cggcctggcc cgggtgatca
aggagcacgc caacgacgaa 840ggacgtcagc tgctggagca actgacggag
atgacaacgg tagacgcagt gatccggatg 900gccggcaggg acatgggtga
cttcctcgac gaaccccttg aggacattct gtcgacgccg 960gaaatttccc
atgtcttcgg cgacaccaag ctgggtagcg cggtgcccac cccgccggta
1020ttgatcgtgc aggccgtgca tgactacctc atcgacgtct ctgacatcga
cgcgctcgct 1080gacagctata cagccggcgg cgccaacgtc acctaccacc
gcgacctgtt cagcgaacat 1140gtgtccctgc acccgctgtc ggccccaatg
acgcttcgct ggctcaccga ccggttcgcc 1200ggcaagccac tgaccgacca
ccgcgtccgg accacgtggc cgaccatctt caacccgatg 1260acctacgccg
gcatggcgag actggccgtg atcgcggcca aggtgatcac cggcaggaag
1320ttgagccgcc gtccgctc 133854630DNAMycobacterium tuberculosis
54atgatcgcca caacccgcga tcgtgaagga gccaccatga tcacgtttag gctgcgcttg
60ccgtgccgga cgatactgcg ggtgttcagc cgcaatccgc tggtgcgtgg gacggatcga
120ctcgaggcgg tcgtcatgct gctggccgtc acggtctcgc tgctgactat
cccgttcgcc 180gccgcggccg gcaccgcagt ccaggattcc cgcagccacg
tctatgccca ccaggcccag 240acccgccatc ccgcaaccgc gaccgtgatc
gatcacgagg gggtgatcga cagcaacacg 300accgccacgt cagcgccgcc
gcgcacgaag atcaccgtgc ctgcccgatg ggtcgtgaac 360ggaatagaac
gcagcggtga ggtcaacgcg aagccgggaa ccaaatccgg tgaccgcgtc
420ggcatttggg tcgacagtgc cggtcagctg gtcgatgaac cagctccgcc
ggcccgtgcc 480attgcggatg cggccctggc cgccttggga ctctggttga
gcgtcgccgc ggttgcgggc 540gccctgctgg cgctcactcg ggcgattctg
atccgcgttc gcaacgccag ttggcaacac 600gacatcgaca gcctgttctg
cacgcagcgg 63055240DNAMycobacterium tuberculosis 55atgaccaacg
tcggtgacca gggggttgac gcggtcttcg gggtgatcta cccacctcag 60gtcgcgctgg
tcagtttcgg caagccggca caacgagttt gcgccgtcga cggcgcgatc
120cacgtcatga cgaccgtgct ggctacgctg cccgctgacc acggctgcag
cgatgaccat 180cgcggcgcgc tgttcttcct gtcgatcaac gagctgacgc
ggtgcgccgc agtaacagga 240561956DNAMycobacterium tuberculosis
56gtgacggtga caccacggac cggcagccgc atcgaggagc tgcttgcacg cagcggccgg
60ttcttcatcc cgggtgagat ctcggcggat ctgcgtaccg tgacccgccg cggcggccgc
120gacggcgacg tgttctatcg agaccggtgg agccacgaca aggtggtccg
ctccacacac 180ggggtgaatt gcaccgggtc gtgttcttgg aagatctacg
tcaaagacga catcatcacc 240tgggagacgc aggagaccga ctatccgtcg
gtgggcccgg accggcccga gtatgagccc 300cgcggctgcc cgcgcggcgc
ggcgttttcc tggtacacgt attcgccgac gcgggtgcgc 360catccgtacg
cccgcggcgt gcttgtcgag atgtatcggg aggcgaaggc acgtttgggt
420gatccggtgg cggcctgggc cgacatccag gccgacccgc ggcggcgccg
ccgctaccag 480cgcgcccgcg gcaagggcgg gctggtccgg gtcagctggg
ccgaggccac cgagatgatc 540gccgccgccc acgtgcacac catctccaca
tacggcccgg accgggttgc cggcttctcc 600cccatcccgg cgatgtccat
ggtgagccac gccgcggggt cgcggttcgt ggagctaatc 660ggcggggtga
tgacgtcgtt ctacgactgg tacgccgacc tgccggtggc ctccccgcag
720gtgttcggcg accagaccga cgtgccggag tccggagatt ggtgggacgt
ggtgtggcaa 780tgcgcctcgg tgctgctgac ctacccgaac tcacggcaac
tcggcaccgc agaggaattg 840ctggcccaca tcgacggtcc ggccgcggat
ctgttggggc gcacggtctc tgagctgcgc 900cgtgccgatc cgctgaccgc
ggcgacccgc tacgtcgaca ccttcgacct gcgaggccgc 960gccaccctgt
acctgaccta ctggaccgcc ggcgacaccc gcaaccgcgg ccgggagatg
1020ctggccttcg cccagaccta ccgcagcacc gacgtcgcac caccgcgcgg
cgagaccccg 1080gacttcctgc cggtggtgct cgaattcgcc gcgaccgtcg
accccgaggc ggggcgacgg 1140ttgctgagcg ggtaccgggt gcccatcgcc
gcgctgtgca atgccctgac cgaggccgca 1200ttgccatacg cacacacggt
ggccgcggta tgccggacgg gtgacatgat gggcgaactc 1260ttctggaccg
tcgtgccgta tgtgacgatg acgatcgtcg cggtcggctc ctggtggcgc
1320taccgctatg acaaattcgg ctggaccacc cgctcgtccc agctgtacga
gtcgcggctg 1380ctgcggatcg ccagcccgat gtttcatttc ggcatcctgg
tggtcatcgt cggccacggt 1440atcgggctcg tgatcccgca gtcgtggact
caggccgccg gtttgagcga gggcgcatat 1500cacgtgcagg ccgtcgtgct
ggggtcgatc gccggcatca ccaccttggc cggcgttacc 1560ctgctgatct
accggcggcg cacccgcggg ccggtgttca tggctaccac cgtcaacgac
1620aaggtgatgt acctcgtgct ggtggcggcg atcgtcgcgg gactgggtgc
gacggcgttg 1680ggctccggcg ttgtcggcga ggcgtacaac taccgcgaga
cggtgtcggt gtggttccgc 1740tcggtgtggg tactgcaacc gcgcggggac
ctgatggccg aggctccgct gtattaccag 1800atccatgtgc tgatcgggtt
ggcgttgttc gcgttgtggc cgttcacccg gctggtacac 1860gcgttcagcg
ccccgatcgg ctatctgttc cgcccgtaca tcatctaccg cagccgcgag
1920gagctggtgc taacgcggcc gcggcggcgc gggtgg
1956571185DNAMycobacterium tuberculosis 57atgagagggc aagcggccaa
tctcgtgctg gccacctgga tctcggtggt caacttctgg 60gcgtggaacc tgatcggccc
gctgtcgacc agctacgcgc gtgacatgtc actgtccagc 120gccgaggcgt
cgctgctcgt cgccaccccg atcctggtgg gtgcccttgg ccgcatcgtc
180accgggccgc tcaccgaccg cttcggcggg cgcgccatgc tcatcgcggt
gacgctggcg 240tcgatcctcc cggtgctcgc ggtcggggtc gcggcaacca
tgggctccta cgcgttgctg 300gtgtttttcg ggctcttcct gggcgttgcc
ggcacgatct tcgccgtcgg catcccgttc 360gccaacaact ggtaccagcc
ggcgcggcgc ggtttctcca ccggcgtgtt cggtatgggc 420atggtcggca
ccgcgctctc ggcgttcttc accccgcggt ttgtacggtg gttcggcctg
480ttcaccaccc acgccatcgt cgcggccgcg ctcgcgtcga ccgccgtggt
ggccatggtc 540gtgcttcgtg atgcacccta ctttcggccc aacgccgacc
cggtgctgcc caggctcaag 600gccgcggcac ggttgccggt gacctgggag
atgtcgtttc tgtacgcgat cgtgttcggc 660gggttcgtgg cgttcagcaa
ctacctgccc acctacatca ccacgatcta cgggttctcc 720acggtcgacg
cgggcgctcg caccgccggg ttcgccctgg cggcggtgct ggcccggccg
780gtgggcgggt ggctctccga ccggatcgca ccgaggcacg tggtgctggc
ctcgctcgcc 840gggaccgcgc tgctggcgtt cgccgcggcg ttgcagccgc
cgccggaggt gtggtcggcg 900gccaccttca tcaccctggc ggtctgcctc
ggcgtgggca ccggcggcgt gttcgcgtgg 960gtggcccgcc gcgccccggc
cgcatcggtc ggctcggtca ccggaatcgt cgccgcggca 1020ggcggattgg
gcggttactt cccgccgctg gtgatgggcg cgacctacga cccggtcgac
1080aacgactaca cggtcgggtt gctgctgctg gtggcgaccg cgctggtcgc
gtgtacctac 1140accgcgctgc acgcgcggga gccggtgagt gaggaggcgt ccagg
118558282DNAMycobacterium tuberculosis 58atgtgcggcg accagtcgga
tcacgtgctg cagcactgga ccgtcgacat atcgatcgac 60gaacacgaag gattgactcg
ggcgaaggca cggctgcgtt ggcgggaaaa ggaattggtg 120ggtgttggcc
tggcaaggct caatccggcc gaccgcaacg tccccgagat cggcgatgaa
180ctctcggtcg cccgagcctt gtccgacttg gggaagcgaa tgttgaaggt
gtcgacccac 240gacatcgaag ctgttaccca tcagccggcg cgattgttgt at
282591680DNAMycobacterium tuberculosis 59atgattccca cgatgacatc
ggccggctgg gcaccagggg tggtgcagtt ccgcgaatac 60caacggcgtt ggctgcgcgg
cgatgtcctc gccggcctga ccgtggccgc ctatctgatc 120ccgcaagcga
tggcgtatgc gaccgtggcg ggcctaccgc cggcagccgg gctgtgggcg
180tcgatcgcgc cgcttgccat ttacgcactg ctcggatcgt cccggcagct
ttcaatcggc 240ccggaatccg ccaccgcctt gatgacggcg gccgtgctcg
ctccgatggc cgccggggat 300cttcgacgct atgccgttct ggcggcaacc
ctcggattgc tagtcggcct tatctgccta 360ctcgctggca cggcgcgact
aggtttcctc gccagcctgc gatcgcggcc ggtgctcgtc 420ggatacatgg
ccggcatcgc gcttgtcatg atctccagcc aactcggcac tatcaccggc
480acctcggtcg aaggcaacga attcttcagc gaagtacact ctttcgcgac
tagcgtcacg 540cgagttcact ggccgacttt tgtgttagcc atgtctgtcc
tagcgctgct aactatgctc 600acgcggtggg cgccgcgcgc ccccggaccg
atcatcgcgg ttcttgcggc cacgatgcta 660gtggccgtta tgtccttgga
tgccaaaggt attgcgattg tgggtcggat accttccggt 720ctgccgacgc
cgggtgtgcc gcccgtttcg gtggaagact tgcgggcact gatcattccg
780gctgccggga tcgcgattgt taccttcacc gacggtgtgt tgaccgcacg
cgccttcgcc 840gctcgtcgag gtcaggaagt caatgccaac gccgagctgc
gcgcggtcgg ggcctgcaac 900atcgccgccg ggctgacaca cggttttccg
gtgagttcca gcagcagccg taccgccctc 960gccgacgtcg tcggtggccg
cacccagctg tactcgctga tcgcgttggg gcttgttgtc 1020atcgtgatgg
ttttcgcgag tgggctgctg gccatgtttc cgatcgccgc tctgggcgct
1080ttggtggtat atgccgcgct acgcttgatc gacttgtcag aattccggcg
actggcgcgg 1140tttcggcgca gcgaactcat gctggcacta gccaccacag
cagccgtgtt aggcctagga 1200gtgttctatg gagtcctcgc cgcggttgcc
ctgtccatcc tcgaactgct tcgtcgggtc 1260gcacatccgc atgacagcgt
tctcgggttc gtgccgggca ttgccggcat gcacgacatc 1320gatgactatc
cgcaggccaa gcgcgtgccc gggctggtgg tgtatcgcta tgacgcgccg
1380ttgtgcttcg ccaatgccga agacttccgc aggcgagcac tgaccgtggt
cgatcaggat 1440ccggggcaag tcgagtggtt cgtactcaac gccgaatcca
atgtggaggt cgacctgact 1500gcgctggatg cgctcgacca actccgcacc
gagctgctgc gtcggggaat agtgttcgcc 1560atggcccggg tcaaacaaga
cttgcgtgaa tcactcaggg ccgccagtct tctcgataag 1620attggcgaag
accatatctt tatgacattg cctaccgcag tgcaggcgtt ccgtcggcgc
168060429DNAMycobacterium tuberculosis 60atgatcacaa acctccgacg
ccgaaccgcg atggcagccg ccggcctagg ggctgctctc 60gggctgggca tcctgctggt
tccgacggtg gacgcccatc tcgccaacgg ttcgatgtcg 120gaagtcatga
tgtcggaaat tgccgggttg cctatccctc cgattatcca ttacggggcg
180attgcctatg cccccagcgg cgcgtcgggc aaagcgtggc accagcgcac
accggcgcga 240gcagagcaag tcgcactaga aaagtgcggt gacaagactt
gcaaagtggt tagtcgcttc 300accaggtgcg gcgcggtcgc ctacaacggc
tcgaaatacc aaggcggaac cggactcacg 360cgccgcgcgg cagaagacga
cgccgtgaac cgactcgaag gcgggcggat cgtcaactgg 420gcgtgcaac
429612715DNAMycobacterium tuberculosis 61ttgtcggcgt cagtgtctgc
cacgacggct catcatggct tgccagcaca tgaagtggtg 60ctgctgctgg agagcgatcc
atatcacggg ctgtccgacg gcgaggccgc ccaacgacta 120gaacgcttcg
ggcccaacac cttggcggtg gtaacgcgcg ctagcttgct ggcccgcatc
180ctgcggcagt ttcatcaccc gctgatctac gttctgctcg ttgccgggac
gatcaccgcc 240ggtcttaagg aattcgttga cgccgcagtg atcttcggtg
tggtggtgat caatgcgatc 300gtgggtttca ttcaagaatc caaggcagag
gccgcactgc agggcctgcg ctccatggtg 360cacacccacg ccaaggtggt
gcgcgagggt cacgagcaca caatgccatc cgaagagctg 420gttcccggtg
accttgtgct gttagcggcc ggtgacaagg ttcccgccga tttgcggctg
480gtgcgacaga ccggattgag cgtgaacgag tcagcactta ccggcgagtc
gacgccggtt 540cacaaggacg aggtggcgtt gccggagggc acaccggtcg
ctgatcgtcg caatatcgcg 600tattccggca cattggtaac cgcgggccat
ggcgccggga tcgtcgtcgc gaccggcgcc 660gaaaccgaac tcggtgagat
tcatcggctc gttggggccg ccgaggttgt cgccacaccg 720ctgaccgcga
agctggcgtg gttcagcaag tttctgacca tcgccatcct gggtctggca
780gcgctcacgt tcggcgtggg tttgctgcgc cggcaagatg ccgtcgaaac
gttcaccgct 840gcgatcgcgc tggcggtcgg ggcaattccc gaaggtctgc
ccaccgccgt gaccatcacc 900ttggccatcg gcatggcccg gatggccaag
cgccgcgcgg tcattcgacg tctacccgcg 960gtggaaacgc tgggcagcac
cacggtcatc tgcgccgaca agaccggaac gctgaccgag 1020aatcagatga
cggtccagtc gatctggaca ccccacggtg agatccgggc gaccggaacg
1080ggctatgcac ccgacgtcct cctgtgcgac accgacgacg cgccggttcc
ggtgaatgcc 1140aatgcggccc ttcgctggtc gctgctggcc ggtgcctgca
gcaacgacgc cgcactggtt 1200cgcgacggca cacgctggca gatcgtcggc
gatcccaccg agggcgcgat gctcgtcgtg 1260gccgccaagg ccggcttcaa
cccggagcgg ctggcgacaa ctctgccgca agtggcagcc 1320ataccgttca
gttccgagcg gcaatacatg gccaccctgc atcgcgacgg gacggatcat
1380gtggtgctgg ccaagggtgc tgtggagcgc atgctcgacc tgtgcggcac
cgagatgggc 1440gccgacggcg cattgcggcc gctggaccgc gccaccgtgt
tgcgtgccac cgaaatgttg 1500acttcccggg ggttgcgggt gctggcaacc
gggatgggtg ccggcgccgg cactcccgac 1560gacttcgacg aaaacgtgat
accaggttcg ctggcgctga ccggcctgca agcgatgagc 1620gatccaccac
gagcggccgc ggcatcggcg gtggcggcct gccacagtgc cggcattgcg
1680gtaaaaatga ttaccggtga ccacgcgggc accgccacgg cgatcgcaac
cgaggtgggg 1740ttgctcgaca acactgaacc ggcggcaggc tcggtcctga
cgggtgccga gctggccgcg 1800ctgagcgcag accagtaccc ggaggccgtg
gatacagcca gcgtgtttgc cagggtctct 1860cccgagcaga agctgcggtt
ggtgcaagca ttgcaggcca gggggcacgt cgtcgcgatg 1920accggcgacg
gcgtcaacga cgccccggcc ttgcgtcagg ccaacattgg cgtcgcgatg
1980ggccgcggtg gcaccgaggt cgccaaggat gccgccgaca tggtgttgac
cgacgacgac 2040ttcgccacca tcgaagccgc ggtcgaggaa ggccgcggcg
tattcgacaa tctgaccaag 2100ttcatcacct ggacgctgcc caccaacctc
ggtgagggcc tagtgatctt ggccgccatc 2160gctgttggcg tcgccttgcc
gattctgccc acccaaattc tgtggatcaa catgaccaca 2220gcgatcgcgc
tcggactcat gctcgcgttc gagcccaagg aggccggaat catgacccgg
2280ccaccgcgcg accccgacca accgctgctg accggctggc ttgtcaggcg
gactcttctg 2340gtttccacct tgctcgtcgc cagcgcgtgg tggctgtttg
catgggagct cgacaatggc 2400gcgggcctgc atgaggcgcg cacggcggcg
ctgaacctgt tcgtcgtcgt cgaggcgttc 2460tatctgttca gctgccggtc
gctgacccga tcggcctggc ggctcggcat gttcgccaac 2520cgctggatca
tcctcggcgt cagtgcgcag gccatcgcgc aattcgcgat cacatatcta
2580cccgcgatga atatggtgtt cgacaccgcg ccaatcgata tcggggtgtg
ggtgcgcata 2640ttcgctgtcg cgaccgcaat cacgattgtg gtggccaccg
acacgctgct gccgagaata 2700cgggcgcaac cgcca
271562774DNAMycobacterium tuberculosis 62atgagtttcc acgatcttca
tcaccaaggt gttccgttcg tgttgcccaa cgcctgggat 60gtgccgtcgg ccctggccta
cctcgcggag ggcttcacgg ctatcggcac aaccagtttc 120ggggtctcgt
ccagcggcgg gcacccggac gggcaccgcg ccactcgcgg cgccaacatc
180gcactggcgg ccgccctggc accgctgcaa tgctacgtca gcgtcgacat
cgaggacgga 240tacagcgacg aacccgacgc cattgctgac tacgtcgcac
aactgtcgac agccggaatc 300aatatcgagg acagtagcgc cgaaaagctc
atcgaccccg ccctggcagc cgctaaaatc 360gttgcgatca aacaacgtaa
ccccgaggtg ttcgtcaacg cccgcgtcga cacctattgg 420ttgcgccagc
acgccgatac caccagcacg atccagcgcg cacttcgcta cgtcgatgcc
480ggcgccgacg gcgtctttgt cccactggcc aacgatcccg acgaacttgc
tgagctcact 540cgcaacattc cgtgcccggt taacacgttg cccgtgcccg
gcttgacgat cgccgacctt 600ggtgagctcg gggtggcccg ggtgtcaacc
ggttcagtgc cctacagcgc ggggttgtat 660gcagcggccc acgcggctcg
ggccgtgagc gacggagagc agctgccacg gtccgtaccg 720tacgccgaac
tgcaggcacg cttggttgac tacgagaacc gcacgagtac aacg
77463855DNAMycobacterium tuberculosis 63gtggtcaagc gctctcgggc
aacccgactt tcgccgagca tctggtccgg atgggaatca 60cctcagtgtc ggtccattcg
ggcgcgattg ctgctacccc ggggtcggtc gcggccgccg 120aacgccgatt
gttgctggaa tcagctcgcg gtgacgcctg acacccggat gccggcatcg
180tcggccgccg ggcgcgacgc ggcggcctac gacgcctggt atgactcacc
caccgggcgg 240ccgatcctgg cgaccgaggt cgccgcgttg cggccgctca
tcgaggtctt tgcccagcca 300cgcttggaaa tcggtgtcgg tacaggacgt
ttcgccgacc tgctcggcgt gcggttcgga 360ctcgatccat cccgtgatgc
gctgatgttc gcacgccggc gcggcgtcct ggtcgccaat 420gccgtcggcg
aggcggtccc tttcgtcagc cggcacttcg gggcggtcct catggcattc
480acgctctgtt tcgtcaccga cccggccgcc atattccggg aaacgcggcg
tctgctcgcc 540gacggcggcg gccttgttat cgggttcttg cctcgcggga
caccgtgggc cgacctgtac 600gctctgcgcg cggcccgcgg acagccaggc
taccgcgacg cccgcttcta caccgcggcc 660gaactcgaac aactgctcgc
agactcggga ttccgggtca tcgcccgccg ctgcacgctg 720caccaaccgc
cgggactcgc ccggtacgac atcgaagccg cccatgacgg tatccaagcc
780ggcgccggct tcgttgctat ctcggcggtc gaccaagcgc acgagcctaa
ggatgatcac 840ccactcgagt cggaa 85564885DNAMycobacterium
tuberculosis 64atgtctaaac cccgcaagca gcacggagtt gtcgtcgggg
tagatggttc gctcgaatcg 60gatgccgccg cctgttgggg tgccaccgat gcggcgatga
ggaacattcc gctgaccgtg 120gtccacgtgg tgaacgccga tgtagcgacg
tggccgccga tgccgtatcc ggagacctgg 180ggggtttggc aggaggacga
gggtcgccag atcgtcgcca acgccgtcaa gctcgccaaa 240gaggcggttg
gagcggatcg aaagctcagc gtaaagagcg agctcgtatt ttccacgccg
300gtacctacca tggttgaaat ctccaacgag gcagagatgg tggtgttggg
cagctcgggc 360cggggagcgc tggcccgagg cttgctcggt tcggtcagct
cgagcctggt gcgacgcgcc 420gggtgcccgg tcgcggtcat ccacagcgat
gatgcggtga tccctgatcc gcagcacgct 480cccgtgctgg tgggaatcga
cggttcgccg gtttcggagc ttgcgacggc ggtggcattt 540gacgaggcgt
cgcgccgcgg cgtcgaactg atcgccgtgc acgcgtggag tgacgtcgaa
600gtggtggaac ttccgggttt ggacttctcg gctgtacagc aggaagcgga
gcttagtctc 660gccgaacgct tggcaggttg gcaagaacgc tatcccgatg
tgccggtgag ccgggttgtc 720gtttgcgatc gcccggcgcg gaagctggtg
caaaagtcgg cgtccgccca gcttgtcgtc
780gttggcagtc atggccgagg tggcttgacc ggcatgcttc tggggtcggt
cagtaacgcg 840gtcttacacg ccgcgcgggt gccagtgatc gtggcacggc agtcg
88565342DNAMycobacterium tuberculosis 65gtgacctatg tgatcggtag
tgagtgcgtg gatgtgatgg acaagtcctg tgtgcaggag 60tgtccggtcg actgtatcta
tgagggcgcc cgaatgctct acatcaaccc cgacgagtgc 120gtggattgtg
gtgcgtgcaa accggcctgc cgcgtcgagg cgatctactg ggaaggcgat
180ctacccgacg atcaacacca gcatctgggg gacaacgccg cctttttcca
ccaagtcctg 240ccgggccgag tggctccgct gggttcgccg ggtggtgccg
cagcggtggg cccgatcgga 300gtcgacacgc ctctggtcgc ggctatcccg
gtggagtgcc ct 34266837DNAMycobacterium tuberculosis 66atgaaccaat
cacacaaacc cccatcgatc gtcgtcggta ttgatggctc gaagccggcc 60gtgcaagccg
cactgtgggc ggtcgacgag gcagccagcc gtgacatccc gctgcgtctg
120ctgtacgcga tcgaacccga cgatcccggg tacgccgcac acggcgcggc
ggctcgcaaa 180ctcgccgccg ccgagaacgc ggtgcgctac gcgttcacag
cggtcgaggc ggcggaccgg 240ccggtcaagg tcgaggtgga gatcacccag
gagcggccgg tcacctcgtt gatccgcgct 300tcggcggctg ctgccctggt
gtgcgttggc gctatcggcg tgcaccactt ccgaccggag 360cgggtgggat
ctaccgcagc ggccctggcg ttatcggcgc agtgcccagt ggcgatcgtg
420cgaccccacc gggtccccat cggacgcgac gccgcatgga tcgtcgtcga
ggcggacggg 480tcgtccgata tcggtgtttt gctgggggcg gtgatggccg
aagcacggct gcgcgactcg 540ccggttcggg tggtcacctg ccggcaatcc
ggagtgggcg ataccgggga cgacgtccgt 600gccagcctgg accgctggct
tgcccgttgg caaccacggt atcccgatgt gcgggtgcaa 660tcggcggcag
tgcacggcga gctgctggat tatctggctg ggctgggtcg atcggtacac
720atggtggtgc tcagcgcgag cgaccaggag catgtggagc aacttgtggg
agcgccgggc 780aacgccgtgt tgcaggaggc cggctgcacc ctgctggtcg
tcggtcagca gtatctg 837671017DNAMycobacterium tuberculosis
67atgacggagc cagcggcgtg ggacgaaggc aagccgcgaa tcatcacttt gaccatgaac
60cccgccttgg acatcacgac gagcgtcgac gtggtgcgcc cgaccgagaa aatgcgttgt
120ggcgcacctc gctacgatcc cggcggcggc ggtatcaatg tcgcccgcat
tgtgcatgtc 180ctcggcggtt gctcgacagc actgttcccg gccggcgggt
cgaccgggag cctgctgatg 240gcgctgctcg gtgatgcggg agtgccattt
cgcgtcattc cgatcgcggc ctcgacgcgg 300gagagcttca cggtcaacga
gtccaggacc gccaagcagt atcgtttcgt gcttccgggg 360ccgtcgctga
ccgtcgcgga gcaggagcaa tgcctcgacg aactgcgcgg tgcggcggct
420tcggccgcct ttgtggtggc cagtggcagc ctgccgccag gtgtggctgc
cgactactat 480cagcgggttg ccgacatctg ccgccgatcg agcactccgc
tgatcctgga tacatctggt 540ggcgggttgc agcacatttc gtccggggtg
tttcttctca aggcgagcgt gcgggaactg 600cgcgagtgcg tcggatccga
actgctgacc gagcccgaac aactggccgc cgcacacgaa 660ctcattgacc
gtgggcgcgc cgaggtcgtg gtggtctcgc ttggatctca gggcgcgcta
720ttggccacac gacatgcgag ccatcgattt tcgtcgattc cgatgaccgc
ggttagcggt 780gtcggcgccg gcgacgcgat ggtggccgcg attaccgtgg
gcctcagccg tggctggtcg 840ctcatcaagt ccgttcgctt gggaaacgcg
gcaggtgcag ccatgctgct gacgccaggc 900accgcggcct gcaatcgcga
cgatgtggag aggttcttcg agctggcggc cgaacccacc 960gaagtcgggc
aggatcaata cgtttggcac ccgatcgtta acccggaagc ctcgcca
1017682043DNAMycobacterium tuberculosis 68gtgctgatga ccgcagcggc
tgatgtcacc cggcgctcgc cgcggcgcgt gttccgtgac 60cgccgcgagg ccggccgggt
gctggcggaa ttactcgccg cctatcggga ccagccggac 120gtgattgtgc
tcggcttggc ccggggtggc ctcccggtcg catgggaggt tgccgcggca
180ctgcatgccc cgctagacgc cttcgtcgtg cgcaaacttg gtgccccggg
gcatgacgag 240ttcgccgttg gtgcactggc cagcggcggc cgcgtcgtgg
tcaatgacga cgtcgtgcgg 300ggcctgcgga tcacaccgca gcaactgcgc
gacatcgccg aacgtgaggg tcgggaactg 360cttcggcgcg agtccgccta
ccgcggcgag cgcccgccca ccgatatcac cggcaagacg 420gtcattgtcg
tcgatgacgg tttggccacc ggcgcaagca tgttcgcggc ggtacaggca
480ttgcgcgatg cgcaaccagc gcagatcgtg attgccgtgc cggcggcgcc
ggagtccacg 540tgccgggagt tcgccggcct cgtcgacgac gttgtgtgcg
cgaccatgcc gaccccgttc 600ctggccgtcg gtgagtcgtt ttgggacttc
cggcaggtca ccgacgagga ggtccgccgg 660ctcctggcca ccccgaccgc
tgggccgtcg ctgcgccggc ccgcggcgtc aacggcggcc 720gatgttctgc
gcagagtcgc gatcgacgcc cccgggggtg ttccgacgca cgaggtgttg
780gcggagctgg tcggcgatgc acgaatcgtg ttgatcggcg aaagctcgca
cggcacacac 840gagttctacc aggcccgggc cgccatgaca cagtggctga
tcgaggagaa gggctttggt 900gcggtagccg ccgaggcgga ctggcccgac
gcctaccggg tcaatcggta cgttcgcggc 960ctcggcgagg acaccaacgc
tgacgaggcg cttagcggat tcgagcggtt tcccgcctgg 1020atgtggcgca
acaccgtggt ccgagatttt gtggaatggc tgcgcacacg caaccagcgc
1080tacgagtcgg gcgcgctgcg gcaagccggc ttctacggtc tggatcttta
cagcctgcat 1140cggtcgatcc aagaggtgat cagctatctc gacaaggtcg
acccgcgtgc ggcggcacgg 1200gcgcgggccc ggtatgcgtg cttcgaccat
gcctgcgccg atgacggtca ggcgtacgga 1260ttcgcggccg cattcggcgc
cggtccgtcg tgcgaacgtg aagccgtcga gcaactggtc 1320gacgttcagc
gcaatgccct ggcgtatgcg cgccaagacg ggctgcttgc cgaggacgaa
1380ctgttctacg cccagcaaaa cgcgcagacg gtgcgcgacg cagaggtgta
ttaccgggcc 1440atgttcagtg gacgcgttac ctcgtggaac ctgcgcgacc
agcacatggc gcagaccctt 1500ggcagtttgc tgacgcattt ggaccgacac
ctcgatgcgc cgccggcgcg aatagtggtg 1560tgggctcata actcccacgt
gggtgacgca cgcgctaccg aggtgtgggc cgacgggcag 1620ctcaccctcg
gccagatagt ccgtgagcga tacggtgacg agtcgcgcag catcggattc
1680agcacgtaca cgggcaccgt caccgcggcc agcgaatggg gtggtatcgc
ccaacgcaaa 1740gcggttcggc cggcactgca cggcagtgtc gaggagctct
tccaccagac tgcagacagt 1800ttcctggtgt cagcgcggct aagccgcgac
gccgaagccc cgctggacgt tgtccggttg 1860ggacgtgcca tcggcgtcgt
ttatctaccg gcaacggaac ggcaaagtca ctacttgcac 1920gtgcggcccg
ccgaccagtt cgacgccatg atccacatcg atcagacccg tgccctggaa
1980cctctcgagg tgacgagccg gtggatcgcc ggcgagaacc cggaaaccta
cccgaccggt 2040ctg 204369432DNAMycobacterium tuberculosis
69atggccacca cccttcccgt tcagcgccac ccgcggtccc tcttccccga gttttctgag
60ctgttcgcgg ccttcccgtc attcgccgga ctccggccca ccttcgacac ccggttgatg
120cggctggaag acgagatgaa agaggggcgc tacgaggtac gcgcggagct
tcccggggtc 180gaccccgaca aggacgtcga cattatggtc cgcgatggtc
agctgaccat caaggccgag 240cgcaccgagc agaaggactt cgacggtcgc
tcggaattcg cgtacggttc cttcgttcgc 300acggtgtcgc tgccggtagg
tgctgacgag gacgacatta aggccaccta cgacaagggc 360attcttactg
tgtcggtggc ggtttcggaa gggaagccaa ccgaaaagca cattcagatc
420cggtccacca ac 43270993DNAMycobacterium tuberculosis 70atgccggaca
ccatggtgac caccgatgtc atcaagagcg cggtgcagtt ggcctgccgc 60gcaccgtcgc
tccacaacag ccagccctgg cgctggatag ccgaggacca cacggttgcg
120ctgttcctcg acaaggatcg ggtgctttac gcgaccgacc actccggccg
ggaagcgctg 180ctggggtgcg gcgccgtact cgaccacttt cgggtggcga
tggcggccgc gggtaccacc 240gccaatgtgg aacggtttcc caaccccaac
gatcctttgc atctggcgtc aattgacttc 300agcccggccg atttcgtcac
cgagggccac cgtctaaggg cggatgcgat cctactgcgc 360cgtaccgacc
ggctgccttt cgccgagccg ccggattggg acttggtgga gtcgcagttg
420cgcacgaccg tcaccgccga cacggtgcgc atcgacgtca tcgccgacga
tatgcgtccc 480gaactggcgg cggcgtccaa actcaccgaa tcgctgcggc
tctacgattc gtcgtatcat 540gccgaactct tttggtggac aggggctttt
gagacttctg agggcatacc gcacagttca 600ttggtatcgg cggccgaaag
tgaccgggtc accttcggac gcgacttccc ggtcgtcgcc 660aacaccgata
ggcgcccgga gtttggccac gaccgctcta aggtcctggt gctctccacc
720tacgacaacg aacgcgccag cctactgcgc tgcggcgaga tgctttccgc
cgtattgctt 780gacgccacca tggctgggct tgccacctgc acgctgaccc
acatcaccga actgcacgcc 840agccgagacc tggtcgcagc gctgattggg
cagcccgcaa ctccgcaagc cttggttcgc 900gtcggtctgg ccccggagat
ggaagagccg ccaccggcaa cgcctcggcg accaatcgat 960gaagtgtttc
acgttcgggc taaggatcac cgg 99371585DNAMycobacterium tuberculosis
71atgccactgc taaccattgg cgatcaattc cccgcctacc agctcaccgc tctcatcggc
60ggtgacctgt ccaaggtcga cgccaagcag cccggcgact acttcaccac tatcaccagt
120gacgaacacc caggcaagtg gcgggtggtg ttcttttggc cgaaagactt
cacgttcgtg 180tgccctaccg agatcgcggc gttcagcaag ctcaatgacg
agttcgagga ccgcgacgcc 240cagatcctgg gggtttcgat tgacagcgaa
ttcgcgcatt tccagtggcg tgcacagcac 300aacgacctca aaacgttacc
cttcccgatg ctctccgaca tcaagcgcga actcagccaa 360gccgcaggtg
tcctcaacgc cgacggtgtg gccgaccgcg tgacctttat cgtcgacccc
420aacaacgaga tccagttcgt ctcggccacc gccggttcgg tgggacgcaa
cgtcgatgag 480gtactgcgag tgctcgacgc cctccagtcc gacgagctgt
gcgcatgcaa ctggcgcaag 540ggcgacccga cgctagacgc tggcgaactc
ctcaaggctt cggcc 58572816DNAMycobacterium tuberculosis 72atgtctggga
gaggagagcc gacgatgaaa acaatcattg ttggtatcga tggttcgcac 60gcggcgatta
cggccgcatt gtggggggtt gacgaggcca tcagccgagc ggtgccgctg
120cgactggtct cagtgatcaa gccgacacat ccgtccccgg acgactacga
ccgcgacctt 180gcgcatgctg aaagatcgct tcgggaagcg cagtccgctg
ttgaggccgc gggcaagctc 240gtcaagatcg aaaccgacat cccccgcggg
ccagccggcc cggtgcttgt ggaggcatcg 300cgcgacgccg agatgatctg
cgtcggctcc gtgggaatcg ggcgctacgc cagctcgatc 360ttgggttcga
cggcaaccga gctggccgaa aaggcgcatt gcccggtcgc cgtcatgcgc
420tcaaaagtgg accagccagc gtctgacatc aactggatcg tggtgcgcat
gaccgacgca 480ccggataacg aggccgtgct ggaatacgct gcccgggaag
cgaagttgcg gcaagcgccc 540atactggcac tcggcgggcg accggaggag
ctccgggaga ttccggacgg cgaattcgaa 600cgtcgcgtgc aggattggca
ccaccgtcat cccgatgtgc gcgtctaccc gatcaccact 660cacacgggta
ttgcccggtt cctggccgac cacgacgagc gcgtacagct ggcagtgatc
720ggcggtggtg aggccggtca gctagcgcgg ctggtcgggc catccggaca
tccggtgttc 780cgtcacgccg agtgttcggt gcttgtcgtt cgccgc
816731179DNAMycobacterium tuberculosis 73atgcgtgatg cgatcccgct
tgggcggatc gccgggtttg tggtgaacgt ccactggagc 60gtgttggtga tcctgtggtt
gttcacctgg agtctggcga ccatgttgcc gggtaccgtc 120ggaggctacc
cggccgtggt ctattggctt ctcggcgcag gtggcgcggt catgttgctg
180gcgtcgctgt tggctcatga gctcgcgcac gccgtcgtcg ctcgtcgcgc
cggggtatcc 240gttgagagcg tgacgttgtg gctgttcggc ggggtgaccg
cgcttggcgg cgaggcaaag 300acgcccaaag ccgctttccg gatcgcgttc
gcgggtccgg ctaccagcct ggcgctgtcg 360gcgacattcg gtgcgttggc
catcacgctc gccggcgtgc ggaccccggc catcgtgatc 420agcgttgctt
ggtggttggc tactgtcaac ctgctgctgg ggctgttcaa tctgctgcct
480ggcgcgccgt tggacggtgg gcggttggtc cgggcctatc tgtggcgccg
ccacggcgat 540agtgtgcgcg ccgggatcgg tgcggcgcgg gccggacggg
tggttgcgct ggtcttgatc 600gcgttgggat tggccgagtt tgtggctggt
ggcctcgtcg gtggggtctg gttagccttc 660attggctggt ttatcttcgc
tgccgctcgc gaggaggaga cccggatttc gacccagcag 720ctgtttgccg
gggtgcgtgt ggccgatgcg atgaccgccc aaccgcatac ggctcccgga
780tggatcaatg tcgaggattt catccagcgt tacgtgcttg gtgaacggca
ctcggcatat 840ccggttgccg atcgggacgg atcgatcacg ggcctggtgg
cattgcggca gctgcgcgat 900gttgcgccta gccggcgcag cactaccagc
gtaggtgaca ttgcgctgcc gctgcacagc 960gtgccgaccg cccgaccaca
agagccgctg accgcgctcc tagagcggat ggcaccgctc 1020ggcccgcgca
gccgtgcgct ggtcaccgaa gggagcgcgg tggtcggcat cgtcactccc
1080agcgatgtcg cgcggctgat tgacgtctac cggttggccc agccggaacc
gacctttacc 1140acgagtcccc aagatgcgga caggttttcc gatgcgggg
1179741239DNAMycobacterium tuberculosis 74atggcaagtt ctgcgagcga
cggcacccac gaacgctcgg cttttcgcct gagtccaccg 60gtcttgagcg gcgccatggg
accgttcatg cacaccggtc tgtacgtcgc tcaatcgtgg 120cgcgactatc
tgggtcaaca gcccgataaa ctgccgatcg cacggcccac tattgcctta
180gcggcgcaag cctttcgaga cgaaatcgtc ctgctgggcc tcaaggcacg
acgtccggtc 240agcaatcatc gagtgttcga gcgcatcagc caagaagtgg
ccgctggact ggagttctat 300gggaatcgca gatggctgga gaagcctagc
ggattttttg cccagccccc accgctcacc 360gaggtcgcgg tccgaaaggt
caaggaccgc agacgctcct tttatcgcat cttcttcgac 420agtgggttta
cgccgcatcc gggtgaaccg ggcagccaac ggtggctctc atacactgcg
480aacaatcgcg agtacgccct gttactgcgg cacccagagc cgcgtccctg
gctggtttgt 540gtacacggca ccgagatggg cagggccccg ttggatctcg
cggtgttccg cgcctggaag 600ctgcatgacg aactcggcct gaacattgtc
atgccggttc ttccgatgca tggtccccgc 660gggcaaggtc tgccgaaggg
cgccgttttt cccggagaag atgttctcga cgatgtgcat 720gggacggctc
aagcggtgtg ggatatccgg cggctgttgt cctggatacg atcgcaggag
780gaggagtcgc tgatcgggtt gaacggtctc tcgctgggcg gctacatcgc
gtcattggtc 840gccagcctcg aagaaggtct cgcctgcgcg attctcggtg
tcccagtggc tgatctgatc 900gagttgttgg gccgccactg cggtcttcgg
cacaaagacc cccgccgcca caccgtcaag 960atggccgaac cgatcggccg
aatgatctcg ccgctctcac ttacgccact ggtgcccatg 1020ccgggccgct
ttatctacgc gggcattgcc gaccgactcg tgcatccacg cgaacaggtg
1080actcgcctct gggagcactg gggcaaaccc gaaatcgtgt ggtatccagg
cggtcacact 1140ggcttcttcc agtcgcggcc ggtacgacgg tttgtccagg
ctgcgctgga gcagtcgggc 1200ctgttggacg cgccacggac acagcgcgac
cgttccgcc 123975360DNAMycobacterium tuberculosis 75atgtccacgc
aacgaccgag gcactccggt attcgggctg ttggccccta cgcatgggcc 60ggccgatgtg
gtcggatagg caggtggggg gtgcaccagg aggcgatgat gaatctagcg
120atatggcacc cgcgcaaggt gcaatccgcc accatctatc aggtgaccga
tcgctcgcac 180gacgggcgca cagcacgggt gcctggtgac gagatcacta
gcaccgtgtc cggttggttg 240tcggagttgg gcacccaaag cccgttggcc
gatgagcttg cgcgtgcggt gcggatcggc 300gactggcccg ctgcgtacgc
aatcggtgag cacctgtccg ttgagattgc cgttgcggtc
360761122DNAMycobacterium tuberculosis 76atgcgatcag aacgtctccg
gtggctggta gccgcagaag gtccgttcgc ctcggtgtat 60ttcgacgact cgcacgacac
tcttgatgcc gtcgagcgcc gggaagcgac gtggcgcgat 120gtccggaagc
atctcgaaag ccgcgacgcg aagcaggagc tcatcgacag cctcgaagag
180gcggtgcggg attctcgacc ggccgtcggc cagcgtggcc gcgcgctgat
cgcgaccggc 240gagcaagtac tggtcaacga gcatctgatc ggcccaccac
cggctacggt gattcggctg 300tcggattatc cgtacgtcgt gccattgata
gaccttgaga tgcggcgacc gacgtatgta 360tttgccgcgg ttgatcacac
cggcgccgac gtcaagctgt atcagggggc caccatcagt 420tccacgaaaa
tcgatggggt cggctacccg gtgcacaagc cggtcaccgc cggctggaac
480ggctacggcg acttccagca caccaccgaa gaagccatcc gaatgaactg
ccgcgcggtc 540gccgaccatc tcacccgact ggtagacgct gccgaccccg
aggtggtgtt cgtgtccggc 600gaggtgcggt cacgcacaga cctgctttcc
acattgccgc agcgggtggc ggtccgggtg 660tcgcagctgc atgccggacc
gcgcaaaagc gccttagacg aggaagagat ctgggacctg 720acatccgcgg
agttcacccg gcggcggtac gccgaaatca ccaatgtcgc acaacaattt
780gaggcggaga tcggacgcgg atcggggctg gcggcccaag ggttggcgga
ggtgtgtgcg 840gctctgcgtg acggcgacgt cgacacgctg atcgtcggag
agctaggcga ggccaccgtg 900gtcaccggta aagcgcgtac tacggtcgcg
cgggatgccg acatgttgtc cgaactcggc 960gaaccggtag atcgcgtggc
aagggccgat gaggcgttgc cattcgccgc gatcgcggta 1020ggtgccgcat
tggtccgtga cgacaaccgg atcgcgccac tagatggggt gggcgcattg
1080ctgcgttatg ccgccaccaa ccgactcggc agccatagat cc
112277537DNAMycobacterium tuberculosis 77atgctgcacc gcgacgatca
catcaatccg ccgcggcccc gcgggttgga tgttccttgc 60gcccgcctac gagcgacaaa
tcccctgcgc gccttggcgc gttgcgttca ggcgggcaag 120ccgggcacca
gttcagggca tcggtccgtg ccgcatacgg cggacttgcg aatcgaagcc
180tgggcaccga cccgtgacgg ctgtatccgg caggcggtgc tgggtaccgt
cgagagcttc 240ctcgacctgg aatccgcgca cgcggtccat acccggctgc
gccggctgac cgcggatcgc 300gacgacgatc tactggtcgc ggtgctcgag
gaggtcattt atttgctgga caccgtcggt 360gaaacgcctg tcgatctcag
gctgcgcgac gttgacgggg gtgtcgacgt cacattcgca 420acgaccgatg
cgagtacgct agttcaggtg ggtgccgtgc cgaaggcggt gtcactcaac
480gaacttcggt tctcgcaggg tcgccacggc tggcgatgtg cggtaacgct cgatgtg
537781125DNAMycobacterium tuberculosis 78gtgacgcaaa ccggcaagcg
tcagagacgc aaattcggtc gcatccgaca gttcaactcc 60ggccgctggc aagccagcta
caccggcccc gacggccgcg tgtacatcgc ccccaaaacc 120ttcaacgcca
agatcgacgc cgaagcatgg ctcaccgacc gccgccgcga aatcgaccga
180caactatggt ccccggcatc gggtcaggaa gaccgccccg gagccccatt
cggtgagtac 240gccgaaggat ggctgaagca gcgtggaatc aaggaccgca
cccgcgccca ctatcgcaaa 300ctgctggaca accacatcct ggccaccttc
gctgacaccg acctacgcga catcaccccg 360gccgccgtgc gccgctggta
cgccaccacc gccgtgggca caccgaccat gcgggcacac 420tcctacagct
tgctgcgcgc aatcatgcag accgccttgg ccgacgacct gatcgactcc
480aacccctgcc gcatctcagg cgcgtccacc gcccgccgcg tccacaagat
caggcccgcc 540accctcgacg agctggaaac catcaccaaa gccatgcccg
acccctacca ggcgttcgtg 600ctgatggcgg catggctggc catgcgctac
ggcgagctga ccgaattacg ccgcaaagac 660atcgacctgc acggcgaggt
tgcgcgggtg cggcgggctg tcgttcgggt gggcgaaggc 720ttcaaggtga
cgacaccgaa aagcgatgcg ggagtgcgcg acataagtat cccgccacat
780ctgatacccg ccatcgaaga ccaccttcac aaacacgtca accccggccg
ggagtccctg 840ctgttcccat cggtcaacga ccccaaccgt cacctagcac
cctcggcgct gtaccgcatg 900ttctacaagg cccgaaaagc cgccggccga
ccagacttac gggtgcacga ccttcgacac 960tccggcgccg tgttggctgc
atccaccggc gccacactgg ccgaactgat gcagcggcta 1020ggacacagca
cagccggcgc cgcactccgc taccagcacg ccgccaaggg ccgggaccgc
1080gaaatcgccg cactgttaag caaactggcc gagaaccagg agatg
1125791113DNAMycobacterium tuberculosis 79atgcgcgtcg gtattccgac
cgagaccaaa aacaacgaat tccgggtggc catcaccccg 60gccggcgtcg cggaactaac
ccgtcgtggc catgaggtgc tcatccaggc aggtgccgga 120gagggctcgg
ctatcaccga cgcggatttc aaggcggcag gcgcgcaact ggtcggcacc
180gccgaccagg tgtgggccga cgctgattta ttgctcaagg tcaaagaacc
gatagcggcg 240gaatacggcc gcctgcgaca cgggcagatc ttgttcacgt
tcttgcattt ggccgcgtca 300cgtgcttgca ccgatgcgtt gttggattcc
ggcaccacgt caattgccta cgagaccgtc 360cagaccgccg acggcgcact
acccctgctt gccccgatga gcgaagtcgc cggtcgactc 420gccgcccagg
ttggcgctta ccacctgatg cgaacccaag ggggccgcgg tgtgctgatg
480ggcggggtgc ccggcgtcga accggccgac gtcgtggtga tcggcgccgg
caccgccggc 540tacaacgcag cccgcatcgc caacggcatg ggcgcgaccg
ttacggttct agacatcaac 600atcgacaaac ttcggcaact cgacgccgag
ttctgcggcc ggatccacac tcgctactca 660tcggcctacg agctcgaggg
tgccgtcaaa cgtgccgacc tggtgattgg ggccgtcctg 720gtgccaggcg
ccaaggcacc caaattagtc tcgaattcac ttgtcgcgca tatgaaacca
780ggtgcggtac tggtggatat agccatcgac cagggcggct gtttcgaagg
ctcacgaccg 840accacctacg accacccgac gttcgccgtg cacgacacgc
tgttttactg cgtggcgaac 900atgcccgcct cggtgccgaa gacgtcgacc
tacgcgctga ccaacgcgac gatgccgtat 960gtgctcgagc ttgccgacca
tggctggcgg gcggcgtgcc ggtcgaatcc ggcactagcc 1020aaaggtcttt
cgacgcacga aggggcgtta ctgtccgaac gggtggccac cgacctgggg
1080gtgccgttca ccgagcccgc cagcgtgctg gcc 111380312DNAMycobacterium
tuberculosis 80atggtcatcc ggtttgatca aatagggtca ttggtcctct
caatgaaatc ccttgcgtca 60ctgtcgtttc agcggtgtct gcgcgagaat tctagtttgg
tcgcggcgct ggaccggctc 120gatgctgcgg tcgatgagct gagcgctttg
tcgtttgatg cgttgaccac tccggagcgg 180gatcgcgccc gtcgcgaccg
ggaccatcat ccttggtccc gctcccgctc gcagttgtcg 240ccacgaatgg
cgcacggtgc agtgcaccaa tgccagtggc cgaaggcggt ttgggctgtc
300attgacaatc ca
312811032DNAMycobacterium tuberculosis 81gtgctcaaga acgcagtctt
gctggcatgc cgggcgccgt cggtgcacaa cagccagccc 60tggcgttggg tggccgaaag
cggctccgag cacactactg tgcacctgtt cgtcaaccgc 120caccgaacgg
tgccggccac cgaccattcc ggccggcaag cgatcatcag ttgcggtgcc
180gtactcgatc accttcgcat cgccatgacg gccgcgcact ggcaggcgaa
tatcactcgc 240tttccccagc cgaaccaacc tgaccagttg gccaccgtcg
aattcagtcc catcgatcac 300gtcacggcgg gacagcgaaa ccgcgcccag
gcgattctgc agcgccgaac cgatcggctt 360ccgtttgaca gcccgatgta
ctggcacctg tttgagcccg cgctgcgcga cgccgtcgac 420aaagacgttg
cgatgcttga tgtggtatcc gacgaccagc gaacacgact ggtggtagcg
480tcacaactca gcgaagtcct gcggcgggac gatccgtact atcacgccga
actcgaatgg 540tggacttcac cgttcgtgct ggcccatggt gtgccgccgg
atacgctggc atcagacgcc 600gaacgcttgc gggttgacct gggccgtgac
ttcccggtcc ggagctacca gaatcgccgt 660gccgagctag ctgatgaccg
atcgaaagtc cttgtgctgt cgacccctag cgacacgcga 720gccgacgcac
tgaggtgtgg cgaagtgctg tcgaccatcc tactcgagtg caccatggcc
780ggcatggcta cctgcacgtt gacccatctg atcgaatcca gtgacagtcg
tgacatcgtg 840cggggcctga cgaggcagcg aggcgagccg caagccttga
tccgggtagg gatagccccg 900ccgttggcag cagttcccgc ccccacacca
cggcggccgc tggacagcgt cttgcagatt 960cgccagacgc ccgagaaagg
gcgtaatgcc tcagatagaa atgcccgtga aacgggttgg 1020ttcagcccgc ct
1032821011DNAMycobacterium tuberculosis 82gtgtggtccg cctcgggtgg
gcagtgcggg aagtatcttg ccgcctcgat ggtgctgcag 60cttgatgggt tggaacgtca
cggtgtgttg gagtttgggc gtgaccgcta tggccccgag 120gtgcgtgagg
agctgttggc gatgagtgcg gccagcatcg atcgttatct gaagaccgcg
180aaggccaaag accagatatc gggtgtgtcg acgacgaaac cctcaccact
gctgcgtaat 240tcgatcaagg ttcgcagggc cggcgatgag gtcgaggcgg
agccggggtt cttcgagggc 300gacaccgtcg cccattgcgg tccgacgctc
aaaggcgagt tcgcccacac cctgaacttg 360accgacgtgc acatcggatg
ggtgttcacc cgcaccgtcc gcaacaacgc ccgtacccac 420atcctcgccg
ggctcaaagc ttctgtcacc gagatcccgc atgggataac gggtttagat
480ttcgacaacg gcaccgtgtt tctcaacaag ccggtcatca gctgggccgg
cgacaacggt 540atctacttca cccgctttcg cccgtacaag aaaaaccact
aggccaccat cgagtccaag 600aacaaccacc tggtccgcaa gtacgcgttc
tactaccgct atgacaccgc cgaggaacgc 660gccgtgctca accggatgtg
gaagctggtc aacgaccgcc tcaactacct caccccgacc 720atcaaaccga
tcgggtatgc cagcagcgcc gacggccgcc gccgacgcct ctacgatgcc
780ccacagacgc cgctggaccg gccactggcc gcaagggtgc tctccgcggc
ccagcaggcc 840gacctgatca cctaccgaga cagcctcaac cccgcccaga
tcggccgcaa aatcgccgac 900ctgcagaacc gactcctcat cttggccaag
gagaaaaccg agcagctcta cctcgctaac 960atccccaccg ccctacccga
catccacaaa ggcatcctga tcaaggcggg c 101183330DNAMycobacterium
tuberculosis 83gtggtgcaag gccgcaccgt gctgtttcgt accgcggagg
gcgccaaatt attttcagcc 60gtcgcgaagt gcgcggtggc tttcgaggcg gacgaccaca
acgttgccga gggctggagc 120gtgatcgtca aggttcgcgc ccaggtgctg
acgaccgacg cgggggtccg cgaagccgaa 180cgcgcccagt tactaccgtg
gaccgcgacg ctgaaacgtc actgtgtgcg ggtgatcccg 240tgggagatca
ccggccgcca cttcaggttc ggtccggaac cggaccgcag ccagaccttt
300gcctgcgagg cctcgtcaca caaccagcga 330841389DNAMycobacterium
tuberculosis 84atgaatcacc taacgacact tgacgccggg tttctcaagg
cagaagacgt ggatcggcac 60gtgagtctgg caatcggcgc tctggcggtc atcgaggggc
cggctcccga tcaggaagcc 120ttcttatcgt cgctcgctca acgcctacgt
ccctgtaccc ggttcgggca gcggttacgc 180ctgcgcccgt tcgacctcgg
tgcacccaaa tgggtggacg atcccgactt cgatcttggc 240cgtcatgtgt
ggcgcatcgc cttgccgcgg cctggcaacg aagaccagtt attcgagctg
300atcgccgatc tgatggcgcg tcgtttggac cggggtcgac cgctgtggga
ggtctgggtc 360atcgaaggcc tggcggacag caagtgggcg atcctgacca
aactgcacca ctgcatggcc 420gacggaatcg cggcgactca cctgctagct
gggctctccg atgaaagtat gagcgacagc 480ttcgcgagca acatccacac
gaccatgcag tcgcaatccg catctgtgcg gcggggtgga 540ttccgtgtca
atccaagcga ggcgttgacc gcgtcgaccg ccgtgatggc aggcatcgtt
600cgcgcggcca agggtgccag tgagatcgcg gccggcgtgc taagtcccgc
cgcgtcgtcg 660ttgaacgggc cgatcagtga tttgcgtcgc tacagcgcag
caaaggtccc tctcgccgac 720gtcgaacagg tgtgccggaa attcgacgtc
accatcaatg atgttgcgct tgccgcgatt 780acggaaagct accgcaacgt
cctcatccag cggggtgagc ggcctaggtt tgattcgctg 840cgtacgctag
tgccggtctc gacgcgttcc aacagcgctt tgagcaagac cgataaccgt
900gtttcgttaa tgctgcccaa cctgccggtg gatcaagaga acccgctgca
gcggctgcgg 960atcgtgcact cgcggctgac tcgggccaag gcggggggac
agagacaatt cggaaatact 1020ttgatggcga ttgccaaccg ccttccgttc
cccatgaccg catgggcggt cgggctgttg 1080atgcggctgc cgcagcgtgg
tgttgtcacc gtggcgacaa atgtgccggg tccacgacgg 1140ccgctgcaga
ttatgggcag acgggtgctt gacctatacc cggtttcgcc gatcgcgatg
1200caactgcgca ccagtgtcgc gatgctcagc tacgccgacg acctgtactt
cgggatcctg 1260gccgactacg acgtggtagc agatgccggc cagctggcgc
gaggaattga agacgccgtc 1320gcacggctgg tggcgatcag taagcggcgc
aaggtgactc gcaggcgcgg agcgctatcg 1380ctggttgtg
138985996DNAMycobacterium tuberculosis 85atgaacaccc atttcccgga
cgccgaaacc gtgcgaacgg ttctcaccct ggccgtccgg 60gccccctcca tccacaacac
gcagccgtgg cggtggcggg tatgcccgac gagtctggag 120ctgttctcta
gacccgatat gcagctgcgt agcaccgatc cggacgggcg tgagttgatc
180ctcagctgtg gtgtggcatt gcaccactgc gtcgtcgctt tggcgtcgct
gggctggcag 240gccaaggtaa accgtttccc cgatcccaag gaccgctgcc
atctggccac catcggggta 300caaccgcttg ttcccgatca ggccgatgtc
gccttggcgg cggccatacc gcggcgacgc 360accgatcggc gcgcctacag
ttgctggccg gtgccaggag gtgacatcgc gttgatggcc 420gcaagagcag
cccgtggcgg ggtcatgctg cggcaggtca gtgccctaga ccgaatgaaa
480gccattgtgg cgcaggctgt cttggaccac gtgaccgacg aggaatatct
gcgcgagctc 540accatttgga gtgggcgcta cggttcagtg gccggggttc
ccgcccgcaa cgagccgcca 600tcagacccca gtgccccgat ccccggtcgc
ctgttcgccg ggcccggtct gtctcagccg 660tccgacgtct tacccgctga
cgacggcgcc gcgatcctgg cactaggcac cgagacagac 720gaccggttgg
cccggctgcg cgccggcgag gccgccagca tcgtcttgtt gaccgcgacg
780gcaatggggc tggcgtgctg cccgatcacc gaaccgctgg agatcgccaa
gacccgcgac 840gcggtccgtg ccgaggtgtt cggcgccggc ggctaccccc
agatgctgct gcgagtgggt 900tgggcaccga tcaatgccga cccgttgcca
ccgacgccac ggcgcgaact gtcccaggtc 960gttgagtggc cggaagagct
actgcgacaa cggtgc 996861734DNAMycobacterium tuberculosis
86atgacaacag ggggcctcgt cgacgaaaac gacggcgccg caatgcgtcc actgcgtcac
60acgctctccc aactacgcct gcacgagctg ctggtcgagg tgcaggaccg ggtcgagcag
120atcgtcgagg gccgggaccg cctcgatggt ctggtggagg ccatgctcgt
ggtcacagcg 180ggcctggacc tggaggcaac cctacgcgct atcgtgcatt
cagcgaccag ccttgtcgat 240gcgcgctatg gcgctatgga ggtgcacgac
cggcagcatc gggtattgca ctttgtctat 300gaaggcatcg acgaggagac
cgttcggcgg atcggccacc taccgaaagg cctaggcgtc 360atcgggctgc
tcatcgaaga tcccaaaccg ttacggctgg acgatgtttc tgcgcacccg
420gcctcgattg gttttccgcc gtatcatccg ccgatgcgta ccttcctcgg
ggtaccggtt 480cgggtgcgcg atgaatcgtt cggcactctg tacctgactg
acaagaccaa cgggcaaccg 540ttcagcgacg acgacgaggt tctggtccag
gcgctggcgg ccgccgcggg tatcgcagtc 600gcgaatgccc ggctctacca
gcaggctaag gcgcgtcagt cgtggatcga ggccacccgt 660gacatcgcca
ccgagttgtt gtccggcacc gaacccgcga cggtgttccg gcttgtcgcc
720gcggaggcgc tcaagctgac ggcggctgac gctgccctgg tagccgttcc
cgtcgacgag 780gacatgcctg ccgctgacgt gggggagctg ctggtgattg
aaacagtcgg cagcgctgtg 840gcttccattg ttgggcgaac gattccggtg
gcgggcgcgg tgctgcggga ggtcttcgtc 900aacggcattc cgcgacgggt
cgaccgggtc gatttggaag gcctggacga actggccgac 960gcaggtccgg
cgctgctgtt gccgctgcgg gccagaggta ccgtagcggg tgtcgttgtt
1020gtgctgagtc aaggcggtcc aggggctttc accgacgaac aactcgagat
gatggccgcg 1080ttcgccgacc aggccgcgct ggcttggcaa ttggccactt
cgcaacgtcg gatgcgcgaa 1140ctcgacgtac tgaccgaccg ggatcgtatc
gcccgtgacc tccatgacca tgtcatccag 1200cggctcttcg cgattggcct
ggctttgcag ggtgctgtcc cgcacgaacg taatcctgaa 1260gtgcagcaac
gactctcgga cgtggtagac gatctgcaag acgttataca ggaaatccgg
1320accaccattt atgacctgca cggagcatcg cagggtatca ctcggctccg
gcagcgaatc 1380gatgcggccg tagcccaatt tgccgactcg gggttgcgca
ccagcgttca attcgtgggt 1440ccattgtcgg tggtcgacag cgcgctcgcc
gatcaggccg aggcggtggt tcgggaagcg 1500gtcagcaacg cggttcgcca
tgcgaaggcc agcacgttga ccgtccgggt caaagtcgac 1560gacgacttgt
gcatcgaggt gaccgacaac ggccgcgggc tgcccgacga gttcaccgga
1620agcggcttaa cgaacctgcg gcagcgggca gagcaggccg gcggcgaatt
caccctcgcg 1680agcgtaccgg gcgcgagcgg aacagtgctg cgatggtcag
caccgttgtc gcag 173487804DNAMycobacterium tuberculosis 87atgagcgatc
ctcggccagc tcgggcagtg gtcgttggta tcgacgggtc aagggcggca 60acgcatgcgg
cgttgtgggc ggtcgatgag gcggtgaacc gagacattcc gctgcgactg
120gtgtacgtca tcgatccgtc ccaactgtcc gccgccggcg agggcggtgg
gcaatcagcg 180gcccgagcgg cgctgcacga cgcctctcgg aaggtcgagg
ccaccgggca accggtcaag 240atcgaaacgg aggttctgtg cggcaggccg
ctcaccaagc tgatgcagga gtccaggtcc 300gcggcgatgc tgtgcgtcgg
ttcggtgggg cttgatcatg tccgcggtcg ccggggttcg 360gtcgcggcga
ccctggctgg gtcggcctta tgccccgtgg cggtgattca cccgtcgccg
420gccgagccag cgacaacctc ccaggtcagc gcggttgtcg cggaggtgga
caatggtgtg 480gtgctgcggc acgcattcga ggaggccagg ctgcgcggag
ttccgctgcg ggccgtggct 540gtccacgctg ctgaaacacc cgatgacgtc
gaacagggca gccggttggc gcatgtacac 600ctgagccgtc ggctcgccca
ctggacccgg ctctaccccg aggtgcgggt ggatcgggcc 660atcgccggcg
gcagtgcgtg ccgtcatctg gccgccaacg caaagccggg tcagctgttc
720gtcgcggact cacactccgc gcacgaattg tgcggtgcat accagcccgg
atgcgccgta 780cttacggtac gcagtgccaa cttg 80488543DNAMycobacterium
tuberculosis 88atgacagaat acgaagggcc taagacaaaa ttccacgcgt
taatgcagga acagattcat 60aacgaattca cagcggcaca acaatatgtc gcgatcgcgg
tttatttcga cagcgaagac 120ctgccgcagt tggcgaagca tttttacagc
caagcggtcg aggaacgaaa ccatgcaatg 180atgctcgtgc aacacctgct
cgaccgcgac cttcgtgtcg aaattcccgg cgtagacacg 240gtgcgaaacc
agttcgacag accccgcgag gcactggcgc tggcgctcga tcaggaacgc
300acagtcaccg accaggtcgg tcggctgaca gcggtggccc gcgacgaggg
cgatttcctc 360ggcgagcagt tcatgcagtg gttcttgcag gaacagatcg
aagaggtggc cttgatggca 420accctggtgc gggttgccga tcgggccggg
gccaacctgt tcgagctaga gaacttcgtc 480gcacgtgaag tggatgtggc
gccggccgca tcaggcgccc cgcacgctgc cgggggccgc 540ctc
54389822DNAMycobacterium tuberculosis 89atgacatggg ccgacgaggt
gctcgccgga catccctttg tggttgctca ccgtggtgcg 60tcggcggctc ggccggagca
tacccttgcc gcctacgacc tggcgctcaa agagggcgcc 120gacggcgtgg
aatgtgatgt gcggttgacc cgggacgggc atctggtctg tgtgcatgac
180cgccgcctgg accgaacctc gacgggagcc ggcttggtca gcacgatgac
gctggcccag 240ctacgcgagc tggagtacgg cgcgtggcac gacagctggc
gccccgacgg ttcgcacggc 300gacaccagtc tgctgaccct ggacgcgctt
gtttcgctgg ttttggactg gcaccggccg 360gtgaagatct tcgtcgagac
caagcatccc gtccgatacg gctcgctggt ggaaaacaag 420ctgctggcgc
tgctacaccg gttcggtatt gccgcacccg cctccgcaga tcgatcccgt
480gcggtggtga tgtcgttttc ggccgccgcg gtctggcgga tccggcgggc
tgcaccgctg 540ctgccgacgg tgttgctcgg caagaccccc cgatacctga
ccagcagtgc ggccacggcg 600gtcggggcaa ccgccgtggg accctcactg
cctgcgttaa aggaatatcc gcaactcgtt 660gaccgctcgg cagctcaggg
ccgggcggtg tactgctgga acgtcgatga gtacgaggac 720atcgactttt
gccgggaggt cggggtggcc tggattggta ctcaccaccc cggccgcacc
780aaggcctggc tggaagacgg gcgggcgaac gggaccactc gc
82290744DNAMycobacterium tuberculosis 90gtgtccgacg gcgaacaagc
caaatcacgt cgacgccggg ggcggcgccg cgggcggcgc 60gctgcggcta cagccgagaa
tcacatggac gcccaaccgg ccggcgacgc caccccgacc 120ccggcaacgg
cgaagcggtc ccggtcccgc tcacctcgtc gcgggtcgac tcggatgcgc
180accgtgcacg aaacatcggc tggagggttg gtcattgacg gtatcgacgg
tccacgagac 240gcgcaggtcg cggctctgat cggccgcgtc gaccggcgcg
gccggctgct gtggtcgcta 300cccaaggggc acatcgagtt gggcgagacc
gccgagcaga ccgccatccg cgaggtcgcc 360gaggagaccg gcatccgcgg
cagtgtgctc gccgcgctgg ggcgcatcga ctactggttc 420gtcaccgacg
gccggcgggt gcacaagacc gtccaccatt atttgatgcg gtttttaggc
480ggagagctgt ccgacgaaga cctcgaggta gccgaggtag cctgggtgcc
gatccgggaa 540ctgccgtctc gactggccta cgccgacgaa cgtcgactag
ccgaggtggc cgacgaactg 600atcgacaagc tgcagagcga cggccccgcc
gcgcttccgc cgctaccacc cagctcgcct 660cgtcgacggc cgcaaacgca
ttcacgcgct cgtcatgccg atgactcagc accgggtcag 720cacaacggtc
ccgggccggg gccg 7449188PRTMycobacterium tuberculosis 91Met Lys Ala
Lys Val Gly Asp Trp Leu Val Ile Lys Gly Ala Thr Ile1 5 10 15Asp Gln
Pro Asp His Arg Gly Leu Ile Ile Glu Val Arg Ser Ser Asp 20 25 30Gly
Ser Pro Pro Tyr Val Val Arg Trp Leu Glu Thr Asp His Val Ala 35 40
45Thr Val Ile Pro Gly Pro Asp Ala Val Val Val Thr Ala Glu Glu Gln
50 55 60Asn Ala Ala Asp Glu Arg Ala Gln His Arg Phe Gly Ala Val Gln
Ser65 70 75 80Ala Ile Leu His Ala Arg Gly Thr
859224DNAArtificialprimer sequence 92caccgtggaa ccgaaacgca gtcg
249319DNAArtificialprimer sequence 93ttatgccaga ccgtcggca
199419DNAArtificialprimer sequence 94caccatgagc ccgggctcg
199520DNAArtificialprimer sequence 95ttacggcgta cgcgagtcag
209624DNAArtificialprimer sequence 96caccgtggag tccgaaccgc tgta
249717DNAArtificialprimer sequence 97ttacgtggcc gagccgc
179822DNAArtificialprimer sequence 98caccatgcct atcgcaacgc cc
229923DNAArtificialprimer sequence 99ttagtgggtt agggactttc cgg
2310049DNAArtificialprimer sequence 100ggggacaagt ttgtacaaaa
aagcaggctt aaaggcaaag gtcggggac 4910150DNAArtificialprimer sequence
101ggggaccact ttgtacaaga aagctgggtc ctacgttccc ctggcatgga
5010222DNAArtificialprimer sequence 102caccatgggt gagcacgcca tc
2210326DNAArtificialprimer sequence 103ttataggtca tcggattgag gtgatc
2610424DNAArtificialprimer sequence 104caccgtggct ggcaatcctg atgt
2410524DNAArtificialprimer sequence 105ttactccttg ctcgttaggt tggc
2410622DNAArtificialprimer sequence 106caccgtgaca gaccacgtgc gc
2210718DNAArtificialprimer sequence 107ttacggtgac gagccggc
1810825DNAArtificialprimer sequence 108caccatggta gagcccggca atttg
2510918DNAArtificialprimer sequence 109ttagagcgga cggcggct
1811022DNAArtificialprimer sequence 110caccatgatc gccacaaccc gc
2211120DNAArtificialprimer sequence 111ttaccgctgc gtgcagaaca
2011224DNAArtificialprimer sequence 112caccatgacc aacgtcggtg acca
2411321DNAArtificialprimer sequence 113ttatcctgtt actgcggcgc a
2111424DNAArtificialprimer sequence 114caccgtgacg gtgacaccac ggac
2411516DNAArtificialprimer sequence 115ttaccacccg cgccgc
1611621DNAArtificialprimer sequence 116caccatgaga gggcaagcgg c
2111722DNAArtificialprimer sequence 117ttacctggac gcctcctcac tc
2211821DNAArtificialprimer sequence 118caccatgtgc ggcgaccagt c
2111921DNAArtificialprimer sequence 119ttaatacaac aatcgcgccg g
2112025DNAArtificialprimer sequence 120caccatgatt cccacgatga catcg
2512117DNAArtificialprimer sequence 121ttagcgccga cggaacg
1712249DNAArtificialprimer sequence 122ggggacaagt ttgtacaaaa
aagcaggctt aatcacaaac ctccgacgc 4912351DNAArtificialprimer sequence
123ggggaccact ttgtacaaga aagctgggtc ctagttgcac gcccagttga c
5112424DNAArtificialprimer sequence 124caccttgtcg gcgtcagtgt ctgc
2412517DNAArtificialprimer sequence 125ttatggcggt tgcgccc
1712629DNAArtificialprimer sequence 126caccatgagt ttccacgatc
ttcatcacc 2912724DNAArtificialprimer sequence 127ttacgttgta
ctcgtgcggt tctc 2412822DNAArtificialprimer sequence 128caccgtggtc
aagcgctctc gg 2212922DNAArtificialprimer sequence 129ttattccgac
tcgagtgggt ga 2213024DNAArtificialprimer sequence 130caccatgtct
aaaccccgca agca 2413119DNAArtificialprimer sequence 131ttacgactgc
cgtgccacg 1913230DNAArtificialprimer sequence 132caccgtgacc
tatgtgatcg gtagtgagtg 3013320DNAArtificialprimer sequence
133ttaagggcac tccaccggga 2013426DNAArtificialprimer sequence
134caccatgaac caatcacaca aacccc 2613525DNAArtificialprimer sequence
135ttacagatac tgctgaccga cgacc 2513620DNAArtificialprimer sequence
136caccatgacg gagccagcgg 2013718DNAArtificialprimer sequence
137ttatggcgag gcttccgg 1813849DNAArtificialprimer sequence
138ggggacaagt ttgtacaaaa aagcaggctt actgatgacc gcagcggct
4913953DNAArtificialprimer sequence 139ggggaccact ttgtacaaga
aagctgggtc ctacagaccg gtcgggtagg ttt 5314048DNAArtificialprimer
sequence 140ggggacaagt ttgtacaaaa aagcaggctt
agccaccacc cttcccgt 4814154DNAArtificialprimer sequence
141ggggaccact ttgtacaaga aagctgggtc ctagttggtg gaccggatct gaat
5414222DNAArtificialprimer sequence 142caccatgccg gacaccatgg tg
2214324DNAArtificialprimer sequence 143ttagtgatcc ttagcccgaa cgtg
2414452DNAArtificialprimer sequence 144ggggacaagt ttgtacaaaa
aagcaggctt aatgccactg ctaaccattg gc 5214552DNAArtificialprimer
sequence 145ggggaccact ttgtacaaga aagctgggtc ctaggccgaa gccttgagga
gt 5214625DNAArtificialprimer sequence 146caccatgtct gggagaggag
agccg 2514721DNAArtificialprimer sequence 147ttagcgaacg acaagcaccg
a 2114848DNAArtificialprimer sequence 148ggggacaagt ttgtacaaaa
aagcaggctt acgtgatgcg atcccgct 4814950DNAArtificialprimer sequence
149ggggaccact ttgtacaaga aagctgggtc ctaccccgca tcggaaaacc
5015051DNAArtificialprimer sequence 150ggggacaagt ttgtacaaaa
aagcaggctt aatggcaagt tctgcgagcg a 5115151DNAArtificialprimer
sequence 151ggggaccact ttgtacaaga aagctgggtc ctaggaacgg tcgcgctgtg
t 5115222DNAArtificialprimer sequence 152caccatgtcc acgcaacgac cg
2215321DNAArtificialprimer sequence 153ttaaccgcaa cggcaatctc a
2115424DNAArtificialprimer sequence 154caccatgcga tcagaacgtc tccg
2415523DNAArtificialprimer sequence 155ttaggatcta tggctgccga gtc
2315621DNAArtificialprimer sequence 156caccatgctg caccgcgacg a
2115723DNAArtificialprimer sequence 157ttacacatcg agcgttaccg cac
2315848DNAArtificialprimer sequence 158ggggacaagt ttgtacaaaa
aagcaggctt agtgacgcaa accggcaa 4815952DNAArtificialprimer sequence
159ggggaccact ttgtacaaga aagctgggtc ctacatctcc tggttctcgg cc
5216049DNAArtificialprimer sequence 160ggggacaagt ttgtacaaaa
aagcaggctt acgcgtcggt attccgacc 4916148DNAArtificialprimer sequence
161ggggaccact ttgtacaaga aagctgggtc ctacacgctg gcgggctc
4816228DNAArtificialprimer sequence 162caccatggtc atccggtttg
atcaaata 2816324DNAArtificialprimer sequence 163ttatggattg
tcaatgacag ccca 2416426DNAArtificialprimer sequence 164caccgtgctc
aagaacgcag tcttgc 2616521DNAArtificialprimer sequence 165ttaaggcggg
ctgaaccaac c 2116620DNAArtificialprimer sequence 166caccgtgtgg
tccgcctcgg 2016720DNAArtificialprimer sequence 167ttagcccgcc
ttgatcagga 2016820DNAArtificialprimer sequence 168caccgtggtg
caaggccgca 2016922DNAArtificialprimer sequence 169ttatcgctgg
ttgtgtgacg ag 2217029DNAArtificialprimer sequence 170caccatgaat
cacctaacga cacttgacg 2917123DNAArtificialprimer sequence
171ttacacaacc agcgatagcg ctc 2317223DNAArtificialprimer sequence
172caccatgaac acccatttcc cgg 2317323DNAArtificialprimer sequence
173ttagcaccgt tgtcgcagta gct 2317423DNAArtificialprimer sequence
174caccatgaca acagggggcc tcg 2317522DNAArtificialprimer sequence
175ttactgcgac aacggtgctg ac 2217622DNAArtificialprimer sequence
176caccatgagc gatcctcggc ca 2217723DNAArtificialprimer sequence
177ttacaagttg gcactgcgta ccg 2317832DNAArtificialprimer sequence
178ccggctgaga tctatgacag aatacgaagg gc 3217924DNAArtificialprimer
sequence 179ccccgccagg gaactagagg cggc 2418022DNAArtificialprimer
sequence 180caccatgaca tgggccgacg ag 2218120DNAArtificialprimer
sequence 181ttagcgagtg gtcccgttcg 2018222DNAArtificialprimer
sequence 182caccgtgtcc gacggcgaac aa 2218315DNAArtificialprimer
sequence 183ttacggcccc ggccc 151848DNAArtificialreference sequence
184agtcagtc 81858DNAArtificialreference sequence 185aatcaatc
81866DNAArtificialreference sequence 186agtgtc
61878DNAArtificialreference sequence 187agtcagtc 8
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