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Chapter 16 : The Proteome of

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Abstract:

The ultimate goal of studying the proteome of is to identify the many proteins that comprise the bacillus and to understand how they behave in concert with each other. This chapter provides an overview of the current understanding of the proteome, including unique aspects, and a description of the approaches being applied. The application of more comprehensive proteomics techniques to was pioneered by Sadamu Nagai. is able to persist in a latent state for long periods under conditions characterized by low oxygen levels, low pH, and nutrient deprivation. In bacteria, proteins are localized to their extracytoplasmic compartments through active protein export systems that selectively translocate the appropriate proteins out of the cytoplasm. As virulence factors and protective antigens are among the exported proteins of , the protein export systems of are important not only to the physiology of the bacillus but also to pathogenesis of disease. The Sec pathway is essential, highly conserved, and the primary pathway for protein transport across the cytoplasmic membrane of bacteria. Annotation of the genome and two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) analyses provides a rough template of proteome function and composition. Application of proteomic techniques to the global identification of posttranslational modifications in has yet to be undertaken and is warranted in the coming phase of proteome research.

Citation: Belisle J, Braunstein M, Rosenkrands I, Andersen P. 2005. The Proteome of , p 235-260. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch16
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Figure 1a

2-D PAGE of the culture filtrate (A), cytosol (B), and cell wall (C) proteins of H37Rv. Reprinted from reference 165 with permission.

Citation: Belisle J, Braunstein M, Rosenkrands I, Andersen P. 2005. The Proteome of , p 235-260. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch16
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Image of Figure 1b
Figure 1b

2-D PAGE of the culture filtrate (A), cytosol (B), and cell wall (C) proteins of H37Rv. Reprinted from reference 165 with permission.

Citation: Belisle J, Braunstein M, Rosenkrands I, Andersen P. 2005. The Proteome of , p 235-260. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch16
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Image of Figure 2
Figure 2

Schematic of the conserved ESAT-6 cluster region 1 of H37Rv. ORFs are depicted as black arrows showing the direction of transcription. The conserved genes in the cluster are boxed. The names of each ORF are listed above the diagram. Predicted transmembrane domains were identified with the Tmpred prediction software ( ).

Citation: Belisle J, Braunstein M, Rosenkrands I, Andersen P. 2005. The Proteome of , p 235-260. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch16
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Image of Figure 3
Figure 3

Triacylated Cys residue of the mature N terminus of the 19-kDa lipoprotein (LpqH [Rv3763]). R1, R2, and R3 indicate palmitic acid, palmitoleic acid, oleic acid, or tuberculostearic acid; with the acylation at each site presumably being heterogeneous.

Citation: Belisle J, Braunstein M, Rosenkrands I, Andersen P. 2005. The Proteome of , p 235-260. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch16
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Figure 4

Alignment of the glycosylation sites of Apa (Rv1860) and MBP83 (Rv2873). “Position” indicates the location of the peptide shown in the mature protein sequence.

Citation: Belisle J, Braunstein M, Rosenkrands I, Andersen P. 2005. The Proteome of , p 235-260. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch16
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References

/content/book/10.1128/9781555817657.chap16
1. Abou-Zeid, C.,, E. Filley,, J. Steele,, and G. A. Rook. 1987. A simple new method for using antigens separated by polyacrylamide gel electrophoresis to stimulate lymphocytes in vitro after converting bands cut from Western blots into antigen-bearing particles. J. Immunol. Methods 98: 5 10.
2. Abou-Zeid, C.,, I. Smith,, J. M. Grange,, T. L. Ratliff,, J. Steele,, and G. A. Rook. 1988. The secreted antigens of Mycobacterium tuberculosis and their relationship to those recognized by the available antibodies. J. Gen. Microbiol. 134: 531 538.
3. Affronti, L. F.,, and F. B. Seibert. 1965. Some early investigations of Mycobacterium tuberculosis. Am. Rev. Respir. Dis. 92: 1 8.
4. Andersen, A. B. 1994. Mycobacterium tuberculosis proteins. Structure, function, and immunological relevance. Dan. Med. Bull. 41: 205 215.
5. Andersen, Å. B.,, and E. B. Hansen. 1989. Structure and mapping of antigenic domains of protein antigen b, a 38,000-molecular-weight protein of Mycobacterium tuberculosis. Infec. Immun. 57: 2481 2488.
6. Andersen, Å. B.,, Z.-L. Yuan,, K. Hasl¢v,, B. Vergmann,, and J. Bennedsen. 1986. Interspecies reactivity of five monoclonal antibodies to Mycobacterium tuberculosis as examined by immunoblotting and enzyme-linked immunosorbent assay. J. Clin. Microbiol. 23: 446 451.
7. Andersen, P.,, Å. B. Andersen,, A. L. Sørensen,, and S. Nagai. 1995. Recall of long-lived immunity to Mycobacterium tuberculosis infection in mice. J. Immunol. 154: 3359 3372.
8. Andersen, P.,, D. Askgaard,, L. Ljungqvist,, J. Bennedsen,, and I. Heron. 1991. Proteins released from Mycobacterium tuberculosis during growth. Infect. Immun. 59: 1905 1910.
9. Andersen, P.,, and I. Heron. 1993. Simultaneous electroelution of whole SDS polyacrylamide gels for the direct cellular analysis of complex protein mixtures. J. Immunol. Methods 161: 29 39.
10. Av-Gay, Y.,, S. Jamil,, and S. J. Drews. 1999. Expression and characterization of the Mycobacterium tuberculosis serine/threonine protein kinase PknB. Infect. Immun. 67: 5676 5682.
11. Banerjee, A.,, E. Dubnau,, A. Quemard,, V. Balasubramanian,, K. S. Um,, T. Wilson,, D. Collins,, G. de Lisle,, and W. R. Jacobs, Jr. 1994. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 263: 227 230.
12. Banu, S.,, N. Honore,, B. Saint-Joanis,, D. Philpott,, M. C. Prevost,, and S. T. Cole. 2002. Are the PE-PGRS proteins of Mycobacterium tuberculosis variable surface antigens? Mol. Microbiol. 44: 9 19.
13. Bao, L.,, W. Chen,, H. Zhang,, and X. Wang. 2003. Virulence, immunogenicity, and protective efficacy of two recombinant Mycobacterium bovis bacillus Calmette-Guérin strains expressing the antigen ESAT-6 from Mycobacterium tuberculosis. Infect. Immun. 71: 1656 1661.
14. Beaucher, J.,, S. Rodrigue,, P. E. Jacques,, I. Smith,, R. Brzezinski,, and L. Gaudreau. 2002. Novel Mycobacterium tuberculosis anti-sigma factor antagonists control sigmaF activity by distinct mechanisms. Mol. Microbiol. 45: 1527 1540.
15. Behr, M. A.,, M. A. Wilson,, W. P. Gill,, H. Salamon,, G. K. Schoolnik,, S. Rane,, and P. M. Small. 1999. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science 284: 1520 1523.
16. Belisle, J. T.,, M. E. Brandt,, J. D. Radolf,, and M. V. Norgard. 1994. Fatty acids of Treponema pallidum and Borrelia burgdorferi lipoproteins. J. Bacteriol. 176: 2151 2157.
17. Belisle, J. T.,, V. D. Vissa,, T. Sievert,, K. Takayama,, P. J. Brennan,, and G. S. Besra. 1997. Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. Science 276: 1420 1422.
18. Bendt, A. K.,, A. Burkovski,, S. Schaffer,, M. Bott,, M. Farwick,, and T. Hermann. 2003. Towards a phosphoproteome map of Corynebacterium glutamicum. Proteomics 3: 1637 1646.
19. Bensing, B. A.,, and P. M. Sullam. 2002. An accessory sec locus of Streptococcus gordonii is required for export of the surface protein GspB and for normal levels of binding to human platelets. Mol. Microbiol. 44: 1081 1094.
20. Benz, I.,, and M. A. Schmidt. 2002. Never say never again: protein glycosylation in pathogenic bacteria. Mol. Microbiol. 45: 267 276.
21. Berthet, F. X.,, P. B. Rasmussen,, I. Rosenkrands,, P. Andersen,, and B. Gicquel. 1998. A Mycobacterium tuberculosis operon encoding ESAT-6 and a novel low-molecular-mass culture filtrate protein (CFP-10). Microbiology 144: 3195 3203.
22. Bessler, W. G.,, W. Baier,, U. vd Esche,, P. Hoffmann,, L. Heinevetter,, K. H. Wiesmuller,, and G. Jung. 1997. Bacterial lipopeptides constitute efficient novel immunogens and adjuvants in parenteral and oral immunization. Behring Inst. Mitt. 98: 390 399.
23. Betts, J. C.,, P. Dodson,, S. Quan,, A. P. Lewis,, P. J. Thomas,, K. Duncan,, and R. A. McAdam. 2000. Comparison of the proteome of Mycobacterium tuberculosis strain H37Rv with clinical isolate CDC 1551. Microbiology 146: 3205 3216.
24. Betts, J. C.,, P. T. Lukey,, L. C. Robb,, R. A. McAdam,, and K. Duncan. 2002. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol. Microbiol. 43: 717 731.
25. Boesen, H.,, B. N. Jensen,, T. Wilcke,, and P. Andersen. 1995. Human T-cell responses to secreted antigen fractions of Mycobacterium tuberculosis. Infect. Immun. 63: 1491 1497.
26. Boitel, B.,, M. Ortiz-Lombardia,, R. Duran,, F. Pompeo,, S. T. Cole,, C. Cervenansky,, and P. M. Alzari. 2003. PknB kinase activity is regulated by phosphorylation in two Thr residues and dephosphorylation by PstP, the cognate phospho-Ser/ Thr phosphatase, in Mycobacterium tuberculosis. Mol. Microbiol. 49: 1493 1508.
27. Boon, C.,, and T. Dick. 2002. Mycobacterium bovis BCG response regulator essential for hypoxic dormancy. J. Bacteriol. 184: 6760 6767.
28. Boon, C.,, R. Li,, R. Qi,, and T. Dick. 2001. Proteins of Mycobacterium bovis BCG induced in the Wayne dormancy model. J. Bacteriol. 183: 2672 2676.
29. Brandt, L.,, M. Elhay,, I. Rosenkrands,, E. B. Lindblad,, and P. Andersen. 2000. ESAT-6 subunit vaccination against Mycobacterium tuberculosis. Infect. Immun. 68: 791 795.
30. Braun, V.,, and H. C. Wu. 1994. Lipoproteins, structure, function, biosynthesis and model for protein export. New Compr. Biochem. 27: 319 341.
31. Braunstein, M.,, and J. T. Belisle,. 2000. Genetics of protein secretion, p. 203 220. In G. F. Hatfull, and W. R. Jacobs (ed.), Molecular Genetics of Mycobacteria. ASM Press, Washington, D.C.
32. Braunstein, M.,, A. M. Brown,, S. Kurtz,, and W. R. Jacobs, Jr. 2001. Two nonredundant SecA homologues function in mycobacteria. J. Bacteriol. 183: 6979 6990.
33. Braunstein, M.,, B. J. Espinosa,, J. Chan,, J. T. Belisle,, and W. R. Jacobs, Jr. 2003. SecA2 functions in the secretion of superoxide dismutase A and in the virulence of Mycobacterium tuberculosis. Mol. Microbiol. 48: 453 464.
34. Braunstein, M.,, T. I. Griffin,, J. I. Kriakov,, S. T. Friedman,, N. D. Grindley,, and W. R. Jacobs, Jr. 2000. Identification of genes encoding exported Mycobacterium tuberculosis proteins using a Tn 552' phoA in vitro transposition system. J. Bacteriol. 182: 2732 2740.
35. Brennan, M. J.,, G. Delogu,, Y. Chen,, S. Bardarov,, J. Kriakov,, M. Alavi,, and W. R. Jacobs, Jr. 2001. Evidence that mycobacterial PE_PGRS proteins are cell surface constituents that influence interactions with other cells. Infect. Immun. 69: 7326 7333.
36. Bryk, R.,, C. D. Lima,, H. Erdjument-Bromage,, P. Tempst,, and C. Nathan. 2002. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science 295: 1073 1077.
37. Camus, J. C.,, M. J. Pryor,, C. Medigue,, and S. T. Cole. 2002. Re-annotation of the genome sequence of Mycobacterium tuberculosis H37Rv. Microbiology 148: 2967 2973.
38. Chaba, R.,, M. Raje,, and P. K. Chakraborti. 2002. Evidence that a eukaryotic-type serine/threonine protein kinase from Mycobacterium tuberculosis regulates morphological changes associated with cell division. Eur. J. Biochem. 269: 1078 1085.
39. Chopra, P.,, A. Singh,, A. Koul,, S. Ramachandran,, K. Drlica,, A. K. Tyagi,, and Y. Singh. 2003. Cytotoxic activity of nucleoside diphosphate kinase secreted from Mycobacterium tuberculosis. Eur. J. Biochem. 270: 625 634.
40. Chopra, P.,, B. Singh,, R. Singh,, R. Vohra,, A. Koul,, L. S. Meena,, H. Koduri,, M. Ghildiyal,, P. Deol,, T. K. Das,, A. K. Tyagi,, and Y. Singh. 2003. Phosphoprotein phosphatase of Mycobacterium tuberculosis dephosphorylates serine-threonine kinases PknA and PknB. Biochem. Biophys. Res. Commun. 311: 112 120.
41. Chow, K.,, D. Ng,, R. Stokes,, and P. Johnson. 1994. Protein tyrosine phosphorylation in Mycobacterium tuberculosis. FEMS Microbiol. Lett. 124: 203 207.
42. Closs, O.,, M. Harboe,, N. H. Axelsen,, K. Bunch-Christensen,, and M. Magnusson. 1980. The antigens of Mycobacterium bovis, strain BCG, studied by crossed immunoelectrophoresis: a reference system. Scand. J. Immunol. 12: 249 263.
43. Cole, S. T.,, R. Brosch,, J. Parkhill,, T. Garnier,, C. Churcher,, D. Harris,, S. V. Gordon,, K. Eiglmeier,, S. Gas,, C. E. Barry III,, F. Tekaia,, K. Badcock,, D. Basham,, D. Brown,, T. Chillingworth,, R. Connor,, R. Davies,, K. Devlin,, T. Feltwell,, S. Gentles,, N. Hamlin,, S. Holroyd,, T. Hornsby,, K. Jagels,, A. Krogh,, J. McLean,, S. Moule,, L. Murphy,, K. Oliver,, J. Osborne,, M. A. Quail,, M.-A. Rajandream,, J. Rogers,, S. Rutter,, K. Seeger,, J. Skelton,, R. Squares,, S. Squares,, J. E. Sulston,, K. Taylor,, S. Whitehead,, and B. G. Barrell. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393: 537 544.
44. Cole, S. T.,, K. Eiglmeier,, J. Parkhill,, K. D. James,, N. R. Thomson,, P. R. Wheeler,, N. Honore,, T. Garnier,, C. Churcher,, D. Harris,, K. Mungall,, D. Basham,, D. Brown,, T. Chillingworth,, R. Connor,, R. M. Davies,, K. Devlin,, S. Duthoy,, T. Feltwell,, A. Fraser,, N. Hamlin,, S. Holroyd,, T. Hornsby,, K. Jagels,, C. Lacroix,, J. Maclean,, S. Moule,, L. Murphy,, K. Oliver,, M. A. Quail,, M.-A. Rajandream,, K. M. Rutherford,, S. Rutter,, K. Seeger,, S. Simon,, M. Simmonds,, J. Skelton,, R. Squares,, S. Squares,, K. Stevens,, K. Taylor,, S. Whitehead,, J. R. Woodward,, and B. G. Barrell. 2001. Massive gene decay in the leprosy bacillus. Nature 409: 1007 1011.
45. Cooper, A. M.,, D. K. Dalton,, T. A. Stewart,, J. P. Griffin,, D. G. Russell,, and I. M. Orme. 1993. Disseminated tuberculosis in interferon gamma gene-disrupted mice. J. Exp. Med. 178: 2243 2247.
46. Covert, B. A.,, J. S. Spencer,, I. M. Orme,, and J. T. Belisle. 2001. The application of proteomics in defining the T cell antigens of Mycobacterium tuberculosis. Proteomics 1: 574 586.
47. Damiani, G.,, A. Biano,, A. Beltrame,, D. Vismara,, M. F. Mezzopreti,, V. Colizzi,, D. B. Young,, and B. R. Bloom. 1988. Generation and characterization of monoclonal antibodies to 28-, 35-, and 65-kilodalton proteins of Mycobacterium tuberculosis. Infec. Immun. 56: 1281 1287.
48. Daniel, T. M. 1989. The chemical composition of immunoaffinity-purified Mycobacterium tuberculosis antigen 5. Am. Rev. Respir. Dis. 139: 1566 1567.
49. Daniel, T. M.,, N. J. Gonchoroff,, J. A. Katzmann,, and G. R. Olds. 1984. Specificity of Mycobacterium tuberculosis antigen 5 determined with mouse monoclonal antibodies. Infect. Immun. 45: 52 55.
50. Daugelat, S.,, J. Kowall,, J. Mattow,, D. Bumann,, R. Winter,, R. Hurwitz,, and S. H. Kaufmann. 2003. The RD1 proteins of Mycobacterium tuberculosis: expression in Mycobacterium smegmatis and biochemical characterization. Microbes Infect. 5: 1082 1095.
51. De Groot, A. S.,, A. Bosma,, N. Chinai,, J. Frost,, B. M. Jesdale,, M. A. Gonzalez,, W. Martin,, and C. Saint-Aubin. 2001. From genome to vaccine: in silico predictions, ex vivo verification. Vaccine 19: 4385 4395.
52. DeLisa, M. P.,, P. Samuelson,, T. Palmer,, and G. Georgiou. 2002. Genetic analysis of the twin arginine translocator secretion pathway in bacteria. J. Biol. Chem. 277: 29825 29831.
53. Deres, K.,, H. Schild,, K. H. Wiesmuller,, G. Jung,, and H. G. Rammensee. 1989. In vivo priming of virus-specific cytotoxic T lymphocytes with synthetic lipopeptide vaccine. Nature 342: 561 564.
54. Deretic, V.,, J. Song,, and E. Pagan-Ramos. 1997. Loss of oxyR in Mycobacterium tuberculosis. Trends Microbiol. 5: 367 372.
55. Dilks, K.,, R. W. Rose,, E. Hartmann,, and M. Pohlschroder. 2003. Prokaryotic utilization of the twin-arginine translocation pathway: a genomic survey. J. Bacteriol. 185: 1478 1483.
56. Dillon, D. C.,, M. R. Alderson,, C. H. Day,, T. Bement,, A. Campos-Neto,, Y. A. Skeiky,, T. Vedvick,, R. Badaro,, S. G. Reed,, and R. Houghton. 2000. Molecular and immunological characterization of Mycobacterium tuberculosis CFP-10, an immunodiagnostic antigen missing in Mycobacterium bovis BCG. J. Clin. Microbiol. 38: 3285 3290.
57. Ding, Z.,, and P. J. Christie. 2003. Agrobacterium tumefaciens twin-arginine-dependent translocation is important for virulence, flagellation, and chemotaxis but not type IV secretion . J. Bacteriol. 185: 760 771.
58. Dobos, K. M.,, K. H. Khoo,, K. M. Swiderek,, P. J. Brennan,, and J. T. Belisle. 1996. Definition of the full extent of glycosylation of the 45-kilodalton glycoprotein of Mycobacterium tuberculosis. J. Bacteriol. 178: 2498 2506.
59. Dobos, K. M.,, K. Swiderek,, K. H. Khoo,, P. J. Brennan,, and J. T. Belisle. 1995. Evidence for glycosylation sites on the 45-kilodalton glycoprotein of Mycobacterium tuberculosis. Infect. Immun. 63: 2846 2853.
60. Downing, K. J.,, R. A. McAdam,, and V. Mizrahi. 1999. Staphylococcus aureus nuclease is a useful secretion reporter for mycobacteria. Gene 239: 293 299.
61. Duong, F.,, and W. Wickner. 1997. Distinct catalytic roles of the SecYE, SecG and SecDFyajC subunits of preprotein translocase holoenzyme. EMBO J. 16: 2756 2768.
62. Economou, A. 1998. Bacterial preprotein translocase: mechanism and conformational dynamics of a processive enzyme. Mol. Microbiol. 27: 511 518.
63. Economou, A.,, and W. Wickner. 1994. SecA promotes preprotein translocation by undergoing ATP-driven cycles of membrane insertion and deinsertion. Cell 78: 835 843.
64. Espitia, C.,, R. Espinosa,, R. Saavedra,, R. Mancilla,, F. Romain,, A. Laqueyrerie,, and C. Moreno. 1995. Antigenic and structural similarities between Mycobacterium tuberculosis 50- to 55-kilodalton and Mycobacterium bovis BCG 45- to 47- kilodalton antigens. Infect. Immun. 63: 580 584.
65. Espitia, C.,, and R. Mancilla. 1989. Identification, isolation and partial characterization of Mycobacterium tuberculosis glycoprotein antigens. Clin. Exp. Immunol. 77: 378 383.
66. Fifis, T.,, C. Costopoulos,, A. J. Radford,, A. Bacic,, and P. R. Wood. 1991. Purification and characterization of major antigens from a Mycobacterium bovis culture filtrate. Infect. Immun. 59: 800 807.
67. Florczyk, M. A.,, L. A. McCue,, R. F. Stack,, C. R. Hauer,, and K. A. McDonough. 2001. Identification and characterization of mycobacterial proteins differentially expressed under standing and shaking culture conditions, including Rv2623 from a novel class of putative ATP-binding proteins. Infect. Immun. 69: 5777 5785.
68. Flory, M. R.,, T. J. Griffin,, D. Martin,, and R. Aebersold. 2002. Advances in quantitative proteomics using stable isotope tags. Trends Biotechnol. 20: S23 S29.V
69. Flynn, J. L.,, J. Chan,, K. J. Triebold,, D. K. Dalton,, T. A. Stewart,, and B. R. Bloom. 1993. An essential role for interferon- gamma in resistance to Mycobacterium tuberculosis infection. J. Exp. Med. 178: 2249 2254.
70. Garbe, T. R.,, N. S. Hibler,, and V. Deretic. 1996. Response of Mycobacterium tuberculosis to reactive oxygen and nitrogen intermediates. Mol. Med. 2: 134 142.
71. Garbe, T. R.,, N. S. Hibler,, and V. Deretic. 1999. Response to reactive nitrogen intermediates in Mycobacterium tuberculosis: induction of the 16-kilodalton alpha-crystallin homolog by exposure to nitric oxide donors. Infect. Immun. 67: 460 465.
72. Ge, Y.,, M. El-Naggar,, S. K. Sze,, H. B. Oh,, T. P. Begley,, F. W. McLafferty,, H. Boshoff,, and C. E. Barry III. 2003. Top down characterization of secreted proteins from Mycobacterium tuberculosis by electron capture dissociation mass spectrometry. J. Am. Soc. Mass. Spectrom. 14: 253 261.
73. Gehring, A. J.,, R. E. Rojas,, D. H. Canaday,, D. L. Lakey,, C. V. Harding,, and W. H. Boom. 2003. The Mycobacterium tuberculosis 19-kilodalton lipoprotein inhibits gamma interferon-regulated HLA-DR and Fc gamma R1 on human macrophages through Toll-like receptor 2. Infect. Immun. 71: 4487 4497.
74. Gey Van Pittius, N. C.,, J. Gamieldien,, W. Hide,, G. D. Brown,, R. J. Siezen,, and A. D. Beyers. 2001. The ESAT-6 gene cluster of Mycobacterium tuberculosis and other high G+C Gram-positive bacteria. Genome Biol. 2: RESEARCH0044. Epub 2001 Sep 19.
75. Gomez, M.,, S. Johnson,, and M. L. Gennaro. 2000. Identification of secreted proteins of Mycobacterium tuberculosis by a bioinformatic approach. Infec. Immun. 68: 2323 2327.
76. Gooley, A. A.,, and K. L. Williams. 1994. Towards characterizing O-glycans: the relative merits of in vivo and in vitro approaches in seeking peptide motifs specifying O-glycosylation sites. Glycobiology 4: 413 417.
77. Goren, M. B.,, and P. J. Brennan,. 1979. Mycobacterial lipids: chemistry and biological activities, p. 63 193. In G. P. Youmans (ed.), Tuberculosis. The W. B. Saunders Co., Philadelphia, Pa.
78. Gorg, A.,, C. Obermaier,, G. Boguth,, A. Harder,, B. Scheibe,, R. Wildgruber,, and W. Weiss. 2000. The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 21: 1037 1053.
79. Griffin, T. J.,, S. P. Gygi,, T. Ideker,, B. Rist,, J. Eng,, L. Hood,, and R. Aebersold. 2002. Complementary profiling of gene expression at the transcriptome and proteome levels in Saccharomyces cerevisiae. Mol. Cell. Proteomics 1: 323 333.
80. Gu, S.,, J. Chen,, K. M. Dobos,, E. M. Bradbury,, J. T. Belisle,, and X. Chen. 2003. Comprehensive proteomic profiling of the membrane constituents of a Mycobacterium tuberculosis strain. Mol. Cell. Proteomics 2: 1284 1296.
81. Guinn, K. M.,, M. J. Hickey,, S. K. Mathur,, K. L. Zakel,, J. E. Grotzke,, D. M. Lewinsohn,, S. Smith,, and D. R. Sherman. Individual RD1-region genes are required for export of ESAT-6/CFP-10 and for virulence of Mycobacterium tuberculosis. Mol. Microbiol. 51: 359 370.
82. Gulle, H.,, B. Schoel,, and S. H. Kaufmann. 1990. Direct blotting with viable cells of protein mixtures separated by twodimensional gel electrophoresis. J. Immunol. Methods 133: 253 261.
83. Hansen, J. E.,, O. Lund,, N. Tolstrup,, A. A. Gooley,, K. L. Williams,, and S. Brunak. 1998. NetOglyc: prediction of mucin type O-glycosylation sites based on sequence context and surface accessibility. Glycoconj. J. 15: 115 130.
84. Harboe, M.,, T. Oettinger,, H. G. Wiker,, I. Rosenkrands,, and P. Andersen. 1996. Evidence for occurrence of the ESAT-6 protein in Mycobacterium tuberculosis and virulent Mycobacterium bovis and for its absence in Mycobacterium bovis BCG. Infect. Immun. 64: 16 22.
85. Harth, G.,, D. L. Clemens,, and M. A. Horwitz. 1994. Glutamine synthetase of Mycobacterium tuberculosis: extracellular release and characterization of its enzymatic activity. Proc. Natl. Acad. Sci. USA 91: 9342 9346.
86. Harth, G.,, and M. A. Horwitz. 1999. Export of recombinant Mycobacterium tuberculosis superoxide dismutase is dependent upon both information in the protein and mycobacterial export machinery. A model for studying export of leaderless proteins by pathogenic mycobacteria. J. Biol. Chem. 274: 4281 4292.
87. Hauschildt, S.,, P. Hoffmann,, H. U. Beuscher,, G. Dufhues,, P. Heinrich,, K. H. Wiesmuller,, G. Jung,, and W. G. Bessler. 1990. Activation of bone marrow-derived mouse macrophages by bacterial lipopeptide: cytokine production, phagocytosis and Ia expression. Eur. J. Immunol. 20: 63 68.
88. Haydel, S. E.,, N. E. Dunlap,, and W. H. Benjamin, Jr. 1999. In vitro evidence of two-component system phosphorylation between the Mycobacterium tuberculosis TrcR/TrcS proteins. Microb. Pathog. 26: 195 206.
89. Hendrickson, R. C.,, J. F. Douglass,, L. D. Reynolds,, P. D. McNeill,, D. Carter,, S. G. Reed,, and R. L. Houghton. 2000. Mass spectrometric identification of mtb81, a novel serological marker for tuberculosis. J. Clin. Microbiol. 38: 2354 2361.
90. Henningsen, R.,, B. L. Gale,, K. M. Straub,, and D. C. DeNagel. 2002. Application of zwitterionic detergents to the solubilization of integral membrane proteins for two-dimensional gel electrophoresis and mass spectrometry. Proteomics 2: 1479 1488.
91. Herrmann, J. L.,, R. Delahay,, A. Gallagher,, B. Robertson,, and D. Young. 2000. Analysis of post-translational modification of mycobacterial proteins using a cassette expression system. FEBS Lett. 473: 358 362.
92. Herrmann, J. L.,, P. O’Gaora,, A. Gallagher,, J. E. Thole,, and D. B. Young. 1996. Bacterial glycoproteins: a link between glycosylation and proteolytic cleavage of a 19 kDa antigen from Mycobacterium tuberculosis. EMBO J. 15: 3547 3554.
93. Hiller, K.,, M. Schobert,, C. Hundertmark,, D. Jahn,, and R. Munch. 2003. JVirGel: calculation of virtual two-dimensional protein gels. Nucleic Acids Res. 31: 3862 3865.
94. Hofmann, K.,, and W. Stoffel. 1993. Tmbase—A database of membrane spanning protein segments. Biol. Chem. Hoppe- Seyler 374: 166 170.
95. Horn, C.,, A. Namane,, P. Pescher,, M. Riviere,, F. Romain,, G. Puzo,, O. Barzu,, and G. Marchal. 1999. Decreased capacity of recombinant 45/47-kDa molecules (Apa) of Mycobacterium tuberculosis to stimulate T lymphocyte responses related to changes in their mannosylation pattern. J. Biol. Chem. 274: 32023 32030.
96. Hsu, T.,, S. M. Hingley-Wilson,, B. Chen,, M. Chen,, A. Z. Dai,, P. M. Morin,, C. B. Marks,, J. Padiyar,, C. Goulding,, M. Gingery,, D. Eisenberg,, R. G. Russell,, S. C. Derrick,, F. M. Collins,, S. L. Morris,, C. H. King,, and W. R. Jacobs, Jr. 2003. The primary mechanism of attenuation of bacillus Calmette-Guérin is a loss of secreted lytic function required for invasion of lung interstitial tissue. Proc. Natl. Acad. Sci. USA 100: 12420 12425.
97. Hunter, S. W.,, B. Rivoire,, V. Mehra,, B. R. Bloom,, and P. J. Brennan. 1990. The major native proteins of the leprosy bacillus. J. Biol. Chem. 265: 14065 14068.
98. Ischiropoulos, H. 2003. Biological selectivity and functional aspects of protein tyrosine nitration. Biochem. Biophys. Res. Commun. 305: 776 783.
99. Jackowski, S.,, and C. O. Rock. 1986. Transfer of fatty acids from the 1 position of phosphatidylethanolamine to the major outer membrane lipoprotein of Escherichia coli. J. Biol. Chem. 261: 1328 1333.
100. Jacobs, W. R., Jr.,, G. V. Kalpana,, J. D. Cirillo,, L. Pascopella,, S. B. Snapper,, R. A. Udani,, W. Jones,, R. G. Barletta,, and B. R. Bloom. 1991. Genetic systems for mycobacteria. Methods Enzymol. 204: 537 555.
101. Jentoft, N. 1990. Why are proteins O-glycosylated? Trends Biochem. Sci. 15: 291 294.
102. Jungblut, P. R.,, E. C. Muller,, J. Mattow,, and S. H. Kaufmann. 2001. Proteomics reveals open reading frames in Mycobacterium tuberculosis H37Rv not predicted by genomics. Infect. Immun. 69: 5905 5907.
103. Jungblut, P. R.,, U. E. Schaible,, H. Mollenkopf,, U. Zimny-Arndt,, B. Raupach,, J. Mattow,, P. Halada,, S. Lamer,, K. Hagens,, and S. H. Kaufmann. 1999. Comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis BCG strains: towards functional genomics of microbial pathogens. Mol. Microbiol. 33: 1103 1117.
104. Kennelly, P. J.,, and M. Potts. 1996. Fancy meeting you here! A fresh look at “prokaryotic” protein phosphorylation. J. Bacteriol. 178: 4759 4764.
105. Khanolkar Young, S.,, A. H. Kolk, Å. B. Andersen, J. Bennedsen, P. J. Brennan, B. Rivoire, S. Kuijper, K. P. McAdam, C. Abe, H. V. Batra, S. D. saras, G. Damiani, M. Singh, and H. D. Engers. 1992. Results of the third immunology of leprosy/immunology of tuberculosis antimycobacterial monoclonal antibody workshop. Infect. Immun. 60: 3925 3927.
106. Klatser, P. R.,, M. Y. De Wit,, A. H. Kolk,, and R. A. Hartskeerl. 1991. Characterization of murine B-cell epitopes on the Mycobacterium leprae proline-rich antigen by use of synthetic peptides. Infect. Immun. 59: 433 436.
107. Koch, R. 1891. Weitere Mitteilung uber das Tuberkulin. Dtsche. Med. Wochnschr. 43: 1189 1192.
108. Koul, A.,, A. Choidas,, M. Treder,, A. K. Tyagi,, K. Drlica,, Y. Singh,, and A. Ullrich. 2000. Cloning and characterization of secretory tyrosine phosphatases of Mycobacterium tuberculosis. J. Bacteriol. 182: 5425 5432.
109. Koul, A.,, A. Choidas,, A. K. Tyagi,, K. Drlica,, Y. Singh,, and A. Ullrich. 2001. Serine/threonine protein kinases PknF and PknG of Mycobacterium tuberculosis: characterization and localization. Microbiology 147: 2307 2314.
110. Kurdistani, S. K.,, and M. Grunstein. 2003. Histone acetylation and deacetylation in yeast. Nat. Rev. Mol. Cell. Biol. 4: 276 284.
111. Laal, S.,, K. M. Samanich,, M. G. Sonnenberg,, J. T. Belisle,, J. O’Leary,, M. S. Simberkoff,, and S. Zolla-Pazner. 1997. Surrogate marker of preclinical tuberculosis in human immunodeficiency virus infection: antibodies to an 88-kDa secreted antigen of Mycobacterium tuberculosis. J. Infect. Dis. 176: 133 143.
112. Lachner, M.,, and T. Jenuwein. 2002. The many faces of histone lysine methylation. Curr. Opin. Cell Biol. 14: 286 298.
113. Lanne, B.,, F. Potthast,, A. Hoglund,, H. Brockenhuus von Lowenhielm,, A. C. Nystrom,, F. Nilsson,, and B. Dahllof. 2001. Thiourea enhances mapping of the proteome from murine white adipose tissue. Proteomics 1: 819 828.
114. Lee, B.-Y.,, and M. A. Horwitz. 1995. Identification of macrophage and stress-induced proteins of Mycobacterium tuberculosis. J. Clin. Investig. 96: 245 249.
115. Lenz, L. L.,, and D. A. Portnoy. 2002. Identification of a second Listeria secA gene associated with protein secretion and the rough phenotype. Mol. Microbiol. 45: 1043 1056.
116. Lewis, K. N.,, R. Liao,, K. M. Guinn,, M. J. Hickey,, S. Smith,, M. A. Behr,, and D. R. Sherman. 2003. Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guérin attenuation. J. Infect. Dis. 187: 117 123.
117. Lim, E. M.,, J. Rauzier,, J. Timm,, G. Torrea,, A. Murray,, B. Gicquel,, and D. Portnoi. 1995. Identification of Mycobacterium tuberculosis DNA sequences encoding exported proteins by using phoA gene fusions. J. Bacteriol. 177: 59 65.
118. Ljungqvist, L.,, A. Worsaae,, and I. Heron. 1988. Antibody responses against Mycobacterium tuberculosis in 11 strains of inbred mice: novel monoclonal antibody specificities generated by fusions, using spleens from BALB.B10 and CBA/J mice. Infect. Immun. 56: 1994 1998.
119. Lowe, J. B.,, and J. D. Marth. 2003. A genetic approach to mammalian glycan function. Annu. Rev. Biochem. 72: 643 691.
120. Lyashchenko, K.,, R. Colangeli,, M. Houde,, H. Al Jahdali,, D. Menzies,, and M. L. Gennaro. 1998. Heterogeneous antibody responses in tuberculosis. Infect. Immun. 66: 3936 3940.
121. Mahairas, G. G.,, P. J. Sabo,, M. J. Hickey,, D. C. Singh,, and C. K. Stover. 1996. Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis. J. Bacteriol. 178: 1274 1282.
122. Mattow, J.,, P. R. Jungblut,, E. C. Muller,, and S. H. Kaufmann. 2001. Identification of acidic, low molecular mass proteins of Mycobacterium tuberculosis strain H37Rv by matrixassisted laser desorption/ionization and electrospray ionization mass spectrometry. Proteomics 1: 494 507.
123. Mattow, J.,, P. R. Jungblut,, U. E. Schaible,, H. J. Mollenkopf,, S. Lamer,, U. Zimny-Arndt,, K. Hagens,, E. C. Muller,, and S. H. Kaufmann. 2001. Identification of proteins from Mycobacterium tuberculosis missing in attenuated Mycobacterium bovis BCG strains. Electrophoresis 22: 2936 2946.
124. Mattow, J.,, U. E. Schaible,, F. Schmidt,, K. Hagens,, F. Siejak,, G. Brestrich,, G. Haeselbarth,, E. C. Muller,, P. R. Jungblut,, and S. H. Kaufmann. 2003. Comparative proteome analysis of culture supernatant proteins from virulent Mycobacterium tuberculosis H37Rv and attenuated M. bovis BCG Copenhagen. Electrophoresis 24: 3405 3420.
125. Menozzi, F. D.,, R. Bischoff,, E. Fort,, M. J. Brennan,, and C. Locht. 1998. Molecular characterization of the mycobacterial heparin-binding hemagglutinin, a mycobacterial adhesin. Proc. Natl. Acad. Sci. USA 95: 12625 12630.
126. Menozzi, F. D.,, J. H. Rouse,, M. Alavi,, M. Laude-Sharp,, J. Muller,, R. Bischoff,, M. J. Brennan,, and C. Locht. 1996. Identification of a heparin-binding hemagglutinin present in mycobacteria. J. Exp. Med. 184: 993 1001.
127. Michell, S. L.,, A. O. Whelan,, P. R. Wheeler,, M. Panico,, R. L. Easton,, A. T. Etienne,, S. M. Haslam,, A. Dell,, H. R. Morris,, A. J. Reason,, J. L. Herrmann,, D. B. Young,, and R. G. Hewinson. 2003. The MPB83 antigen from Mycobacterium bovis contains O-linked mannose and (1→3)-mannobiose moieties. J. Biol. Chem. 278: 16423 16432.
128. Modlin, R. L. 2001. Activation of toll-like receptors by microbial lipoproteins: role in host defense. J. Allergy Clin. Immunol. 108: S104 S106.
129. Molle, V.,, C. Girard-Blanc,, L. Kremer,, P. Doublet,, A. J. Cozzone,, and J. F. Prost. 2003. Protein PknE, a novel transmembrane eukaryotic-like serine/threonine kinase from Mycobacterium tuberculosis. Biochem. Biophys. Res. Commun. 308: 820 825.
130. Mollenkopf, H. J.,, P. R. Jungblut,, B. Raupach,, J. Mattow,, S. Lamer,, U. Zimny-Arndt,, U. E. Schaible,, and S. H. Kaufmann. 1999. A dynamic two-dimensional polyacrylamide gel electrophoresis database: the mycobacterial proteome via Internet. Electrophoresis 20: 2172 2180.
131. Monahan, I. M.,, J. Betts,, D. K. Banerjee,, and P. D. Butcher. 2001. Differential expression of mycobacterial proteins following phagocytosis by macrophages. Microbiology 147: 459 471.
132. Nagai, S.,, J. Matsumoto,, and T. Nagasuga. 1981. Specific skin-reactive protein from culture filtrate of Mycobacterium bovis BCG. Infect. Immun. 31: 1152 1160.
133. Nagai, S.,, H. G. Wiker,, M. Harboe,, and M. Kinomoto. 1991. Isolation and partial characterization of major protein antigens in the culture fluid of Mycobacterium tuberculosis. Infec. Immun. 59: 372 382.
134. Navarre, W. W.,, and O. Schneewind. 1999. Surface proteins of gram-positive bacteria and mechanisms of their targeting to the cell wall envelope. Microbiol. Mol. Biol. Rev. 63: 174 229.
135. Nielsen, H.,, J. Engelbrecht,, S. Brunak,, and G. von Heijne. 1997. A neural network method for identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Int. J. Neural. Syst. 8: 581 599.
136. Noss, E. H.,, R. K. Pai,, T. J. Sellati,, J. D. Radolf,, J. Belisle,, D. T. Golenbock,, W. H. Boom,, and C. V. Harding. 2001. Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis. J. Immunol. 167: 910 918.
137. Ochsner, U. A.,, A. Snyder,, A. I. Vasil,, and M. L. Vasil. 2002. Effects of the twin-arginine translocase on secretion of virulence factors, stress response, and pathogenesis. Proc. Natl. Acad. Sci. USA 99: 8312 8317.
138. O’Donnell, M. A.,, A. Aldovini,, R. B. Duda,, H. Yang,, A. Szilvasi,, R. A. Young,, and W. C. DeWolf. 1994. Recombinant Mycobacterium bovis BCG secreting functional interleukin-2 enhances gamma interferon production by splenocytes. Infect. Immun. 62: 2508 2514.
139. Ohno, H.,, G. Zhu,, V. P. Mohan,, D. Chu,, S. Kohno,, W. R. Jacobs, Jr.,, and J. Chan. 2003. The effects of reactive nitrogen intermediates on gene expression in Mycobacterium tuberculosis. Cell. Microbiol. 5: 637 648.
140. Okkels, L. M.,, I. Brock,, F. Follmann,, E. M. Agger,, S. M. Arend,, T. H. M. Ottenhoff,, F. Oftung,, I. Rosenkrands,, and P. Andersen. 2003. PPE protein (Rv3873) from DNA segment RD1 of Mycobacterium tuberculosis: strong recognition of both specific T-cell epitopes and epitopes conserved within the PPE family. Infect. Immun. 71: 6116 6123.
141. Okkels, L. M.,, T. M. Doherty,, and P. Andersen. 2003. Selecting the components for a safe and efficient tuberculosis subunit vaccine—recent progress and post-genomic insights. Curr. Pharm. Biotechnol. 4: 69 83.
142. Owens, M. U.,, W. E. Swords,, M. G. Schmidt,, C. H. King,, and F. D. Quinn. 2002. Cloning, expression, and functional characterization of the Mycobacterium tuberculosis secA gene. FEMS Microbiol. Lett. 211: 133 141.
143. Pallen, M. J. 2002. The ESAT-6/WXG100 superfamily—and a new Gram-positive secretion system? Trends Microbiol. 10: 209 212.
144. Park, H. D.,, K. M. Guinn,, M. I. Harrell,, R. Liao,, M. I. Voskuil,, M. Tompa,, G. K. Schoolnik,, and D. R. Sherman. 2003. Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis. Mol. Microbiol. 48: 833 843.
145. Peirs, P.,, L. De Wit,, M. Braibant,, K. Huygen,, and J. Content. 1997. A serine/threonine protein kinase from Mycobacterium tuberculosis. Eur. J. Biochem. 244: 604 612.
146. Peirs, P.,, B. Parmentier,, L. De Wit,, and J. Content. 2000. The Mycobacterium bovis homologous protein of the Mycobacterium tuberculosis serine/threonine protein kinase Mbk (PknD) is truncated. FEMS Microbiol. Lett. 188: 135 139.
147. Peng, J.,, J. E. Elias,, C. C. Thoreen,, L. J. Licklider,, and S. P. Gygi. 2003. Evaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) for large-scale protein analysis: the yeast proteome. J. Proteome Res. 2: 43 50.
148. Pethe, K.,, P. Bifani,, H. Drobecq,, C. Sergheraert,, A. S. Debrie,, C. Locht,, and F. D. Menozzi. 2002. Mycobacterial heparin-binding hemagglutinin and laminin-binding protein share antigenic methyllysines that confer resistance to proteolysis. Proc. Natl. Acad. Sci. USA 99: 10759 10764.
149. Petrickova, K.,, and M. Petricek. 2003. Eukaryotic-type protein kinases in Streptomyces coelicolor: variations on a common theme. Microbiology 149: 1609 1621.
150. Plano, G. V.,, J. B. Day,, and F. Ferracci. 2001. Type III export: new uses for an old pathway. Mol. Microbiol. 40: 284 293.
151. Pollock, J. M.,, and P. Andersen. 1997. Predominant recognition of the ESAT-6 protein in the first phase of infection with Mycobacterium bovis in cattle. Infec. Immun. 65: 2587 2592.
152. Pradel, N.,, C. Ye,, V. Livrelli,, J. Xu,, B. Joly,, and L. F. Wu. 2003. Contribution of the twin arginine translocation system to the virulence of enterohemorrhagic Escherichia coli O157:H7. Infect. Immun. 71: 4908 4916.
153. Pruess, M.,, W. Fleischmann,, A. Kanapin,, Y. Karavidopoulou,, P. Kersey,, E. Kriventseva,, V. Mittard,, N. Mulder,, I. Phan,, F. Servant,, and R. Apweiler. 2003. The Proteome Analysis database: a tool for the in silico analysis of whole proteomes. Nucleic Acids Res. 31: 414 417.
154. Pugsley, A. P. 1993. The complete general secretory pathway in gram-negative bacteria. Microbiol. Rev. 57: 50 108.
155. Pym, A. S.,, P. Brodin,, R. Brosch,, M. Huerre,, and S. T. Cole. 2002. Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti. Mol. Microbiol. 46: 709 717.
156. Pym, A. S.,, P. Brodin,, L. Majlessi,, R. Brosch,, C. Demangel,, A. Williams,, K. E. Griffiths,, G. Marchal,, C. Leclerc,, and S. T. Cole. 2003. Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis. Nat. Med. 9: 533 539.
157. Ravn, P.,, A. Demissie,, T. Eguale,, H. Wondwosson,, D. Lein,, H. A. Amoudy,, A. S. Mustafa,, A. K. Jensen,, A. Holm,, I. Rosenkrands,, F. Oftung,, J. Olobo,, F. von Reyn,, and P. Andersen. 1999. Human T cell responses to the ESAT-6 antigen from Mycobacterium tuberculosis. J. Infect. Dis. 179: 637 645.
158. Raynaud, C.,, G. Etienne,, P. Peyron,, M. A. Laneelle,, and M. Daffe. 1998. Extracellular enzyme activities potentially involved in the pathogenicity of Mycobacterium tuberculosis. Microbiology 144: 577 587.
159. Raynaud, C.,, C. Guilhot,, J. Rauzier,, Y. Bordat,, V. Pelicic,, R. Manganelli,, I. Smith,, B. Gicquel,, and M. Jackson. 2002. Phospholipases C are involved in the virulence of Mycobacterium tuberculosis. Mol. Microbiol. 45: 203 217.
160. Renshaw, P. S.,, P. Panagiotidou,, A. Whelan,, S. V. Gordon,, R. G. Hewinson,, R. A. Williamson,, and M. D. Carr. 2002. Conclusive evidence that the major T-cell antigens of the Mycobacterium tuberculosis complex ESAT-6 and CFP-10 form a tight, 1:1 complex and characterization of the structural properties of ESAT-6, CFP-10, and the ESAT-6*CFP- 10 complex. Implications for pathogenesis and virulence. J. Biol. Chem. 277: 21598 21603.
161. Rodrigue, A.,, A. Chanal,, K. Beck,, M. Muller,, and L. F. Wu. 1999. Co-translocation of a periplasmic enzyme complex by a hitchhiker mechanism through the bacterial tat pathway. J. Biol. Chem. 274: 13223 13228.
162. Romain, F.,, C. Horn,, P. Pescher,, A. Namane,, M. Riviere,, G. Puzo,, O. Barzu,, and G. Marchal. 1999. Deglycosylation of the 45/47-kilodalton antigen complex of Mycobacterium tuberculosis decreases its capacity to elicit in vivo or in vitro cellular immune responses. Infect. Immun. 67: 5567 5572.
163. Rosenkrands, I.,, A. King,, K. Weldingh,, M. Moniatte,, E. Moertz,, and P. Andersen. 2000. Towards the proteome of Mycobacterium tuberculosis. Electrophoresis 21: 3740 3756.
164. Rosenkrands, I.,, R. A. Slayden,, J. Crawford,, C. Aagaard,, C. E. Barry III,, and P. Andersen. 2002. Hypoxic response of Mycobacterium tuberculosis studied by metabolic labelling and proteome analysis of cellular and extracellular proteins. J. Bacteriol. 184: 3485 3491.
165. Rosenkrands, I.,, K. Weldingh,, S. Jacobsen,, C. V. Hansen,, W. Florio,, I. Gianetri,, and P. Andersen. 2000. Mapping and identification of Mycobacterium tuberculosis proteins by two-dimensional gel electrophoresis, microsequencing and immunodetection. Electrophoresis 21: 935 948.
166. Roskoski, R., Jr. 2003. Protein prenylation: a pivotal posttranslational process. Biochem. Biophys. Res. Commun. 303: 1 7.
167. Saleh, M. T.,, M. Fillon,, P. J. Brennan,, and J. T. Belisle. 2001. Identification of putative exported/secreted proteins in prokaryotic proteomes. Gene 269: 195 204.
168. Samanich, K.,, J. T. Belisle,, and S. Laal. 2001. Homogeneity of antibody responses in tuberculosis patients. Infect. Immun. 69: 4600 4609.
169. Samanich, K. M.,, J. T. Belisle,, M. G. Sonnenberg,, M. A. Keen,, S. Zolla-Pazner,, and S. Laal. 1998. Delineation of human antibody responses to culture filtrate antigens of Mycobacterium tuberculosis. J. Infect. Dis. 178: 1534 1538.
170. Samanich, K. M.,, M. A. Keen,, V. D. Vissa,, J. D. Harder,, J. S. Spencer,, J. T. Belisle,, S. Zolla-Pazner,, and S. Laal. 2000. Serodiagnostic potential of culture filtrate antigens of Mycobacterium tuberculosis. Clin. Diagn. Lab. Immunol. 7: 662 668.
171. Samuelson, J. C.,, M. Chen,, F. Jiang,, I. Moller,, M. Wiedmann,, A. Kuhn,, G. J. Phillips,, and R. E. Dalbey. 2000. YidC mediates membrane protein insertion in bacteria. Nature 406: 637 641.
172. Santini, C. L.,, B. Ize,, A. Chanal,, M. Muller,, G. Giordano,, and L. F. Wu. 1998. A novel sec-independent periplasmic protein translocation pathway in Escherichia coli. EMBO J. 17: 101 112.
173. Sargent, F.,, E. G. Bogsch,, N. R. Stanley,, M. Wexler,, C. Robinson,, B. C. Berks,, and T. Palmer. 1998. Overlapping functions of components of a bacterial Sec-independent protein export pathway. EMBO J. 17: 3640 3650.
174. Sassetti, C. M.,, D. H. Boyd,, and E. J. Rubin. 2003. Genes required for mycobacterial growth defined by high density mutagenesis. Mol. Microbiol. 48: 77 84.
175. Sassetti, C. M.,, and E. J. Rubin. 2003. Genetic requirements for mycobacterial survival during infection. Proc. Natl. Acad. Sci. USA 100: 12989 12994.
176. Schiebel, E.,, A. J. Driessen,, F. U. Hartl,, and W. Wickner. 1991. Delta mu H + and ATP function at different steps of the catalytic cycle of preprotein translocase. Cell 64: 927 939.
177. Schmidt, M. A.,, L. W. Riley,, and I. Benz. 2003. Sweet new world: glycoproteins in bacterial pathogens. Trends Microbiol. 11: 554 561.
178. Schmidt, M. G.,, and K. B. Kiser. 1999. SecA: the ubiquitous component of preprotein translocase in prokaryotes. Microbes Infect. 1: 993 1004.
179. Schneider, G. 1999. How many potentially secreted proteins are contained in a bacterial genome? Gene 237: 113 121.
180. Seibert, F. B.,, and J. T. Glenn. 1941. Tuberculin purified protein derivative: preparation and analyses of a large quantity for standard. Am. Rev. Tuberc. 44: 9 25.
181. Sherman, D. R.,, P. J. Sabo,, M. J. Hickey,, T. M. Arain,, G. G. Mahairas,, Y. Yuan,, C. E. Barry III,, and C. K. Stover. 1995. Disparate responses to oxidative stress in saprophytic and pathogenic mycobacteria. Proc. Natl. Acad. Sci. USA 92: 6625 6629.
182. Sherman, D. R.,, M. Voskuil,, D. Schnappinger,, R. Liao,, M. I. Harrell,, and G. K. Schoolnik. 2001. Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding alpha-crystallin. Proc. Natl. Acad. Sci. USA 98: 7534 7539.
183. Singh, R.,, V. Rao,, H. Shakila,, R. Gupta,, A. Khera,, N. Dhar,, A. Singh,, A. Koul,, Y. Singh,, M. Naseema,, P. R. Narayanan,, C. N. Paramasivan,, V. D. Ramanathan,, and A. K. Tyagi. 2003. Disruption of mptpB impairs the ability of Mycobacterium tuberculosis to survive in guinea pigs. Mol. Microbiol. 50: 751 762.
184. Skjot, R. L.,, T. Oettinger,, I. Rosenkrands,, P. Ravn,, I. Brock,, S. Jacobsen,, and P. Andersen. 2000. Comparative evaluation of low-molecular-mass proteins from Mycobacterium tuberculosis identifies members of the ESAT-6 family as immunodominant T-cell antigens. Infect. Immun. 68: 214 220.
185. Smith, C. V.,, C. C. Huang,, A. Miczak,, D. G. Russell,, J. C. Sacchettini,, and K. Honer zu Bentrup. 2003. Biochemical and structural studies of malate synthase from Mycobacterium tuberculosis. J. Biol. Chem. 278: 1735 1743.
186. Sonnenberg, M. G.,, and J. T. Belisle. 1997. Definition of Mycobacterium tuberculosis culture filtrate proteins by twodimensional polyacrylamide gel electrophoresis, N-terminal amino acid sequencing, and electrospray mass spectrometry. Infect. Immun. 65: 4515 4524.
187. Sørensen, A. L.,, S. Nagai,, G. Houen,, P. Andersen, and Å. B. Andersen. 1995. Purification and characterization of a lowmolecular- mass T-cell antigen secreted by Mycobacterium tuberculosis. Infect. Immun. 63: 1710 1717.
188. Stanley, N. R.,, T. Palmer,, and B. C. Berks. 2000. The twin arginine consensus motif of Tat signal peptides is involved in Sec-independent protein targeting in Escherichia coli. J. Biol. Chem. 275: 11591 11596.
189. Stanley, S. A.,, S. Raghavan,, W. W. Hwang,, and J. S. Cox. 2003. Acute infection and macrophage subversion by Mycobacterium tuberculosis require a specialized secretion system. Proc. Natl. Acad. Sci. USA 100: 13001 13006.
190. Stock, A. M.,, V. L. Robinson,, and P. N. Goudreau. 2000. Two-component signal transduction. Annu. Rev. Biochem. 69: 183 215.
191. Stock, J. B.,, A. M. Stock,, and J. M. Mottonen. 1990. Signal transduction in bacteria. Nature 344: 395 400.
192. Sutcliffe, I. C.,, and R. R. Russell. 1995. Lipoproteins of gram-positive bacteria. J. Bacteriol. 177: 1123 1128.
193. Tekaia, F.,, S. V. Gordon,, T. Garnier,, R. Brosch,, B. G. Barrell,, and S. T. Cole. 1999. Analysis of the proteome of Mycobacterium tuberculosis in silico. Tubercle Lung Dis. 79: 329 342.
194. Terada, M.,, T. Kuroda,, S. I. Matsuyama,, and H. Tokuda. 2001. Lipoprotein sorting signals evaluated as the LolAdependent release of lipoproteins from the cytoplasmic membrane of Escherichia coli. J. Biol. Chem. 276: 47690 47694.
195. Thoma-Uszynski, S.,, S. M. Kiertscher,, M. T. Ochoa,, D. A. Bouis,, M. V. Norgard,, K. Miyake,, P. J. Godowski,, M. D. Roth,, and R. L. Modlin. 2000. Activation of toll-like receptor 2 on human dendritic cells triggers induction of IL-12, but not IL-10. J. Immunol. 165: 3804 3810.
196. Thoma-Uszynski, S.,, S. Stenger,, O. Takeuchi,, M. T. Ochoa,, M. Engele,, P. A. Sieling,, P. F. Barnes,, M. Rollinghoff,, P. L. Bolcskei,, M. Wagner,, S. Akira,, M. V. Norgard,, J. T. Belisle,, P. J. Godowski,, B. R. Bloom,, and R. L. Modlin. 2001. Induction of direct antimicrobial activity through mammalian toll-like receptors. Science 291: 1544 1547.
197. Tobian, A. A.,, N. S. Potter,, L. Ramachandra,, R. K. Pai,, M. Convery,, W. H. Boom,, and C. V. Harding. 2003. Alternate class I MHC antigen processing is inhibited by Toll-like receptor signaling pathogen-associated molecular patterns: Mycobacterium tuberculosis 19-kDa lipoprotein, CpG DNA, and lipopolysaccharide. J. Immunol. 171: 1413 1422.
198. Tullius, M. V.,, G. Harth,, and M. A. Horwitz. 2001. High extracellular levels of Mycobacterium tuberculosis glutamine synthetase and superoxide dismutase in actively growing cultures are due to high expression and extracellular stability rather than to a protein-specific export mechanism. Infect. Immun. 69: 6348 6363.
199. Urquhart, B. L.,, S. J. Cordwell,, and I. Humphery-Smith. 1998. Comparison of predicted and observed properties of proteins encoded in the genome of Mycobacterium tuberculosis H37Rv. Biochem. Biophys. Res. Commun. 253: 70 79.
200. Valent, Q. A.,, P. A. Scotti,, S. High,, J. W. de Gier,, G. von Heijne,, G. Lentzen,, W. Wintermeyer,, B. Oudega,, and J. Luirink. 1998. The Escherichia coli SRP and SecB targeting pathways converge at the translocon. EMBO J. 17: 2504 2512.
201. Verbon, A.,, S. Kuijper,, H. M. Jansen,, P. Speelman,, and A. H. Kolk. 1990. Antigens in culture supernatant of Mycobacterium tuberculosis: epitopes defined by monoclonal and human antibodies. J. Gen. Microbiol. 136: 955 964.
202. Verstijnen, C. P.,, R. Schoningh,, S. Kuijper,, J. Bruins,, R. J. von Ketel,, D. G. Groothuis,, and A. H. Kolk. 1989. Rapid identification of cultured Mycobacterium tuberculosis with a panel of monoclonal antibodies in western blot and immunofluorescence. Res. Microbiol. 140: 653 666.
203. Via, L. E.,, R. Curcic,, M. H. Mudd,, S. Dhandayuthapani,, R. J. Ulmer,, and V. Deretic. 1996. Elements of signal transduction in Mycobacterium tuberculosis: in vitro phosphorylation and in vivo expression of the response regulator MtrA. J. Bacteriol. 178: 3314 3321.
204. Voskuil, M. I.,, D. Schnappinger,, K. C. Visconti,, M. I. Harrell,, G. M. Dolganov,, D. R. Sherman,, and G. K. Schoolnik. 2003. Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J. Exp. Med. 198: 705 713.
205. Wards, B. J.,, G. W. de Lisle,, and D. M. Collins. 2000. An esat6 knockout mutant of Mycobacterium bovis produced by homologous recombination will contribute to the development of a live tuberculosis vaccine. Tubercle Lung Dis. 80: 185 189.
206. Weiner, J. H.,, P. T. Bilous,, G. M. Shaw,, S. P. Lubitz,, L. Frost,, G. H. Thomas,, J. A. Cole,, and R. J. Turner. 1998. A novel and ubiquitous system for membrane targeting and secretion of cofactor-containing proteins. Cell 93: 93 101.
207. Weldingh, K.,, I. Rosenkrands,, S. Jacobsen,, P. B. Rasmussen,, M. J. Elhay,, and P. Andersen. 1998. Two-dimensional electrophoresis for analysis of Mycobacterium tuberculosis culture filtrate and purification and characterization of six novel proteins. Infect. Immun. 66: 3492 3500.
208. Wiker, H. G.,, M. Harboe,, J. Bennedsen,, and O. Closs. 1988. The antigens of Mycobacterium tuberculosis, H37Rv, studied by crossed immunoelectrophoresis. Comparison with a reference system for Mycobacterium bovis BCG. Scand. J. Immunol. 27: 223 239.
209. Wiker, H. G.,, M. Harboe,, and T. E. Lea. 1986. Purification and characterization of two protein antigens from the heterogeneous BCG85 complex in Mycobacterium bovis BCG. Int. Arch. Allergy Appl. Immunol. 81: 298 306.
210. Wiker, H. G.,, M. Harboe,, and S. Nagai. 1991. A localization index for distinction between extracellular and intracellular antigens of Mycobacterium tuberculosis. J. Gen. Microbiol. 137: 875 884.
211. Wiker, H. G.,, M. A. Wilson,, and G. K. Schoolnik. 2000. Extracytoplasmic proteins of Mycobacterium tuberculosis—mature secreted proteins often start with aspartic acid and proline. Microbiology 146: 1525 1533.
212. Wilson, M.,, J. DeRisi,, H. H. Kristensen,, P. Imboden,, S. Rane,, P. O. Brown,, and G. K. Schoolnik. 1999. Exploring drug-induced alterations in gene expression in Mycobacterium tuberculosis by microarray hybridization. Proc. Natl. Acad. Sci. USA 96: 12833 12838.
213. Wong, D. K.,, B. Y. Lee,, M. A. Horwitz,, and B. W. Gibson. 1999. Identification of Fur, aconitase, and other proteins expressed by Mycobacterium tuberculosis under conditions of low and high concentrations of iron by combined twodimensional gel electrophoresis and mass spectrometry. Infect. Immun. 67: 327 336.
214. Yahr, T. L.,, and W. T. Wickner. 2001. Functional reconstitution of bacterial Tat translocation in vitro. EMBO J. 20: 2472 2479.
215. Yeats, C.,, R. D. Finn,, and A. Bateman. 2002. The PASTA domain: a beta-lactam-binding domain. Trends Biochem. Sci. 27: 438.
216. Yen, M. R.,, Y. H. Tseng,, E. H. Nguyen,, L. F. Wu,, and M. H. Saier, Jr. 2002. Sequence and phylogenetic analyses of the twin-arginine targeting (Tat) protein export system. Arch. Microbiol. 177: 441 450.
217. Yeremeev, V. V.,, I. V. Lyadova,, B. V. Nikonenko,, A. S. Apt,, C. Abou-Zeid,, J. Inwald,, and D. B. Young. 2000. The 19-kD antigen and protective immunity in a murine model of tuberculosis. Clin. Exp. Immunol. 120: 274 279.
218. Yim, M. B.,, H. S. Yim,, C. Lee,, S. O. Kang,, and P. B. Chock. 2001. Protein glycation: creation of catalytic sites for free radical generation. Ann. N.Y. Acad. Sci. 928: 48 53.
219. Young, D.,, and T. R. Garbe. 1991. Heat shock proteins and antigens of Mycobacterium tuberculosis. Infec. Immun. 59: 3086 3093.
220. Young, D. B.,, and T. R. Garbe. 1991. Lipoprotein antigens of Mycobacterium tuberculosis. Res. Microbiol. 142: 55 65.
221. Young, D. B.,, S. H. Kaufmann,, P. W. Hermans,, and J. E. Thole. 1992. Mycobacterial protein antigens: a compilation. Mol. Microbiol. 6: 133 145.
222. Young, D. B.,, and J. R. Lamb. 1986. T lymphocytes respond to solid-phase antigen: a novel approach to the molecular analysis of cellular immunity. Immunology 59: 167 171.
223. Young, T. A.,, B. Delagoutte,, J. A. Endrizzi,, A. M. Falick,, and T. Alber. 2003. Structure of Mycobacterium tuberculosis PknB supports a universal activation mechanism for Ser/Thr protein kinases. Nat. Struct. Biol. 10: 168 174.
224. Yuan, Y.,, D. D. Crane,, R. M. Simpson,, Y. Q. Zhu,, M. J. Hickey,, D. R. Sherman,, and C. E. Barry III. 1998. The 16-kDa alpha-crystallin (Acr) protein of Mycobacterium tuberculosis is required for growth in macrophages. Proc. Natl. Acad. Sci. USA 95: 9578 9583.
225. Zahrt, T. C.,, C. Wozniak,, D. Jones,, and A. Trevett. 2003. Functional analysis of the Mycobacterium tuberculosis MprAB two-component signal transduction system. Infect. Immun. 71: 6962 6970.
226. Zhang, Y.,, B. Heym,, B. Allen,, D. Young,, and S. Cole. 1992. The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature 358: 591 593.
227. Zhang, Y.,, R. Lathigra,, T. Garbe,, D. Catty,, and D. Young. 1991. Genetic analysis of superoxide dismutase, the 23 kilodalton antigen of Mycobacterium tuberculosis. Mol. Microbiol. 5: 381 391.
228. Zhu, H.,, M. Bilgin,, R. Bangham,, D. Hall,, A. Casamayor,, P. Bertone,, N. Lan,, R. Jansen,, S. Bidlingmaier,, T. Houfek,, T. Mitchell,, P. Miller,, R. A. Dean,, M. Gerstein,, and M. Snyder. 2001. Global analysis of protein activities using proteome chips. Science 293: 2101 2105.

Tables

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Table 1

Known phosphorylated proteins of

Citation: Belisle J, Braunstein M, Rosenkrands I, Andersen P. 2005. The Proteome of , p 235-260. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch16
Generic image for table
Table 2

T-cell antigens identified via proteomics

Citation: Belisle J, Braunstein M, Rosenkrands I, Andersen P. 2005. The Proteome of , p 235-260. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch16