Chapter 16 : The Proteome of

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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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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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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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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 98:510.
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. 134:531538.
3. Affronti, L. F.,, and F. B. Seibert. 1965. Some early investigations of Mycobacterium tuberculosis. Am. Rev. Respir. Dis. 92:18.
4. Andersen, A. B. 1994. Mycobacterium tuberculosis proteins. Structure, function, and immunological relevance. Dan. Med. Bull. 41:205215.
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. 57:24812488.
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. 23:446451.
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. 154:33593372.
8. Andersen, P.,, D. Askgaard,, L. Ljungqvist,, J. Bennedsen,, and I. Heron. 1991. Proteins released from Mycobacterium tuberculosis during growth. Infect. Immun. 59:19051910.
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 161:2939.
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. 67:56765682.
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 263:227230.
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. 44:919.
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. 71:16561661.
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. 45:15271540.
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 284:15201523.
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. 176:21512157.
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 276:14201422.
18. Bendt, A. K.,, A. Burkovski,, S. Schaffer,, M. Bott,, M. Farwick,, and T. Hermann. 2003. Towards a phosphoproteome map of Corynebacterium glutamicum. Proteomics 3:16371646.
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. 44:10811094.
20. Benz, I.,, and M. A. Schmidt. 2002. Never say never again: protein glycosylation in pathogenic bacteria. Mol. Microbiol. 45:267276.
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 144:31953203.
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. 98:390399.
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 146:32053216.
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. 43:717731.
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. 63:14911497.
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. 49:14931508.
27. Boon, C.,, and T. Dick. 2002. Mycobacterium bovis BCG response regulator essential for hypoxic dormancy. J. Bacteriol. 184:67606767.
28. Boon, C.,, R. Li,, R. Qi,, and T. Dick. 2001. Proteins of Mycobacterium bovis BCG induced in the Wayne dormancy model. J. Bacteriol. 183:26722676.
29. Brandt, L.,, M. Elhay,, I. Rosenkrands,, E. B. Lindblad,, and P. Andersen. 2000. ESAT-6 subunit vaccination against Mycobacterium tuberculosis. Infect. Immun. 68:791795.
30. Braun, V.,, and H. C. Wu. 1994. Lipoproteins, structure, function, biosynthesis and model for protein export. New Compr. Biochem. 27:319341.
31. Braunstein, M.,, and J. T. Belisle,. 2000. Genetics of protein secretion, p. 203220. 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. 183:69796990.
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. 48:453464.
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 Tn552' phoA in vitro transposition system. J. Bacteriol. 182:27322740.
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. 69:73267333.
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 295:10731077.
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 148:29672973.
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. 269:10781085.
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. 270:625634.
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. 311:112120.
41. Chow, K.,, D. Ng,, R. Stokes,, and P. Johnson. 1994. Protein tyrosine phosphorylation in Mycobacterium tuberculosis. FEMS Microbiol. Lett. 124:203207.
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. 12:249263.
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 393:537544.
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 409:10071011.
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. 178:22432247.
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 1:574586.
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. 56:12811287.
48. Daniel, T. M. 1989. The chemical composition of immunoaffinity-purified Mycobacterium tuberculosis antigen 5. Am. Rev. Respir. Dis. 139:15661567.
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. 45:5255.
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. 5:10821095.
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 19:43854395.
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. 277:2982529831.
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 342:561564.
54. Deretic, V.,, J. Song,, and E. Pagan-Ramos. 1997. Loss of oxyR in Mycobacterium tuberculosis. Trends Microbiol. 5:367372.
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. 185:14781483.
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. 38:32853290.
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. 185:760771.
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. 178:24982506.
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. 63:28462853.
60. Downing, K. J.,, R. A. McAdam,, and V. Mizrahi. 1999. Staphylococcus aureus nuclease is a useful secretion reporter for mycobacteria. Gene 239:293299.
61. Duong, F.,, and W. Wickner. 1997. Distinct catalytic roles of the SecYE, SecG and SecDFyajC subunits of preprotein translocase holoenzyme. EMBO J. 16:27562768.
62. Economou, A. 1998. Bacterial preprotein translocase: mechanism and conformational dynamics of a processive enzyme. Mol. Microbiol. 27:511518.
63. Economou, A.,, and W. Wickner. 1994. SecA promotes preprotein translocation by undergoing ATP-driven cycles of membrane insertion and deinsertion. Cell 78:835843.
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. 63:580584.
65. Espitia, C.,, and R. Mancilla. 1989. Identification, isolation and partial characterization of Mycobacterium tuberculosis glycoprotein antigens. Clin. Exp. Immunol. 77:378383.
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. 59:800807.
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. 69:57775785.
68. Flory, M. R.,, T. J. Griffin,, D. Martin,, and R. Aebersold. 2002. Advances in quantitative proteomics using stable isotope tags. Trends Biotechnol. 20:S23S29.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. 178:22492254.
70. Garbe, T. R.,, N. S. Hibler,, and V. Deretic. 1996. Response of Mycobacterium tuberculosis to reactive oxygen and nitrogen intermediates. Mol. Med. 2:134142.
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. 67:460465.
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. 14:253261.
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. 71:44874497.
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. 68:23232327.
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 4:413417.
77. Goren, M. B.,, and P. J. Brennan,. 1979. Mycobacterial lipids: chemistry and biological activities, p. 63193. 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 21:10371053.
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 1:323333.
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 2:12841296.
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. 51:359370.
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 133:253261.
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. 15:115130.
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. 64:1622.
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 91:93429346.
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. 274:42814292.
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. 20:6368.
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. 26:195206.
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. 38:23542361.
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 2:14791488.
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. 473:358362.
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. 15:35473554.
93. Hiller, K.,, M. Schobert,, C. Hundertmark,, D. Jahn,, and R. Munch. 2003. JVirGel: calculation of virtual two-dimensional protein gels. Nucleic Acids Res. 31:38623865.
94. Hofmann, K.,, and W. Stoffel. 1993. Tmbase—A database of membrane spanning protein segments. Biol. Chem. Hoppe- Seyler 374:166170.
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. 274:3202332030.
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 100:1242012425.
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. 265:1406514068.
98. Ischiropoulos, H. 2003. Biological selectivity and functional aspects of protein tyrosine nitration. Biochem. Biophys. Res. Commun. 305:776783.
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. 261:13281333.
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. 204:537555.
101. Jentoft, N. 1990. Why are proteins O-glycosylated? Trends Biochem. Sci. 15:291294.
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. 69:59055907.
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. 33:11031117.
104. Kennelly, P. J.,, and M. Potts. 1996. Fancy meeting you here! A fresh look at “prokaryotic” protein phosphorylation. J. Bacteriol. 178:47594764.
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. 60:39253927.
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. 59:433436.
107. Koch, R. 1891. Weitere Mitteilung uber das Tuberkulin. Dtsche. Med. Wochnschr. 43:11891192.
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. 182:54255432.
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 147:23072314.
110. Kurdistani, S. K.,, and M. Grunstein. 2003. Histone acetylation and deacetylation in yeast. Nat. Rev. Mol. Cell. Biol. 4:276284.
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. 176:133143.
112. Lachner, M.,, and T. Jenuwein. 2002. The many faces of histone lysine methylation. Curr. Opin. Cell Biol. 14:286298.
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 1:819828.
114. Lee, B.-Y.,, and M. A. Horwitz. 1995. Identification of macrophage and stress-induced proteins of Mycobacterium tuberculosis. J. Clin. Investig. 96:245249.
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. 45:10431056.
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. 187:117123.
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. 177:5965.
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. 56:19941998.
119. Lowe, J. B.,, and J. D. Marth. 2003. A genetic approach to mammalian glycan function. Annu. Rev. Biochem. 72:643691.
120. Lyashchenko, K.,, R. Colangeli,, M. Houde,, H. Al Jahdali,, D. Menzies,, and M. L. Gennaro. 1998. Heterogeneous antibody responses in tuberculosis. Infect. Immun. 66:39363940.
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. 178:12741282.
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 1:494507.
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 22:29362946.
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 24:34053420.
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 95:1262512630.
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. 184:9931001.
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. 278:1642316432.
128. Modlin, R. L. 2001. Activation of toll-like receptors by microbial lipoproteins: role in host defense. J. Allergy Clin. Immunol. 108:S104S106.
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. 308:820825.
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 20:21722180.
131. Monahan, I. M.,, J. Betts,, D. K. Banerjee,, and P. D. Butcher. 2001. Differential expression of mycobacterial proteins following phagocytosis by macrophages. Microbiology 147:459471.
132. Nagai, S.,, J. Matsumoto,, and T. Nagasuga. 1981. Specific skin-reactive protein from culture filtrate of Mycobacterium bovis BCG. Infect. Immun. 31:11521160.
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. 59:372382.
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. 63:174229.
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. 8:581599.
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. 167:910918.
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 99:83128317.
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. 62:25082514.
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. 5:637648.
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. 71:61166123.
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. 4:6983.
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. 211:133141.
143. Pallen, M. J. 2002. The ESAT-6/WXG100 superfamily—and a new Gram-positive secretion system? Trends Microbiol. 10:209212.
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. 48:833843.
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. 244:604612.
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. 188:135139.
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. 2:4350.
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 99:1075910764.
149. Petrickova, K.,, and M. Petricek. 2003. Eukaryotic-type protein kinases in Streptomyces coelicolor: variations on a common theme. Microbiology 149:16091621.
150. Plano, G. V.,, J. B. Day,, and F. Ferracci. 2001. Type III export: new uses for an old pathway. Mol. Microbiol. 40:284293.
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. 65:25872592.
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. 71:49084916.
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. 31:414417.
154. Pugsley, A. P. 1993. The complete general secretory pathway in gram-negative bacteria. Microbiol. Rev. 57:50108.
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. 46:709717.
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: 533539.
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. 179:637645.
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 144:577587.
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. 45:203217.
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. 277:2159821603.
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. 274:1322313228.
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. 67:55675572.
163. Rosenkrands, I.,, A. King,, K. Weldingh,, M. Moniatte,, E. Moertz,, and P. Andersen. 2000. Towards the proteome of Mycobacterium tuberculosis. Electrophoresis 21:37403756.
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. 184:34853491.
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 21:935948.
166. Roskoski, R., Jr. 2003. Protein prenylation: a pivotal posttranslational process. Biochem. Biophys. Res. Commun. 303:17.
167. Saleh, M. T.,, M. Fillon,, P. J. Brennan,, and J. T. Belisle. 2001. Identification of putative exported/secreted proteins in prokaryotic proteomes. Gene 269:195204.
168. Samanich, K.,, J. T. Belisle,, and S. Laal. 2001. Homogeneity of antibody responses in tuberculosis patients. Infect. Immun. 69:46004609.
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. 178:15341538.
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. 7:662668.
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 406:637641.
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. 17:101112.
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. 17:36403650.
174. Sassetti, C. M.,, D. H. Boyd,, and E. J. Rubin. 2003. Genes required for mycobacterial growth defined by high density mutagenesis. Mol. Microbiol. 48:7784.
175. Sassetti, C. M.,, and E. J. Rubin. 2003. Genetic requirements for mycobacterial survival during infection. Proc. Natl. Acad. Sci. USA 100:1298912994.
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 64:927939.
177. Schmidt, M. A.,, L. W. Riley,, and I. Benz. 2003. Sweet new world: glycoproteins in bacterial pathogens. Trends Microbiol. 11:554561.
178. Schmidt, M. G.,, and K. B. Kiser. 1999. SecA: the ubiquitous component of preprotein translocase in prokaryotes. Microbes Infect. 1:9931004.
179. Schneider, G. 1999. How many potentially secreted proteins are contained in a bacterial genome? Gene 237:113121.
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. 44:925.
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: 66256629.
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 98:75347539.
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. 50:751762.
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. 68:214220.
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. 278:17351743.
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. 65:45154524.
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. 63:17101717.
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. 275:1159111596.
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 100:1300113006.
190. Stock, A. M.,, V. L. Robinson,, and P. N. Goudreau. 2000. Two-component signal transduction. Annu. Rev. Biochem. 69:183215.
191. Stock, J. B.,, A. M. Stock,, and J. M. Mottonen. 1990. Signal transduction in bacteria. Nature 344:395400.
192. Sutcliffe, I. C.,, and R. R. Russell. 1995. Lipoproteins of gram-positive bacteria. J. Bacteriol. 177:11231128.
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. 79:329342.
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. 276:4769047694.
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. 165:38043810.
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 291:15441547.
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. 171:14131422.
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. 69:63486363.
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. 253:7079.
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. 17:25042512.
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. 136:955964.
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. 140:653666.
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. 178:33143321.
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. 198:705713.
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. 80:185189.
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 93:93101.
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. 66:34923500.
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. 27:223239.
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. 81:298306.
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. 137:875884.
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 146:15251533.
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 96:1283312838.
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. 67:327336.
214. Yahr, T. L.,, and W. T. Wickner. 2001. Functional reconstitution of bacterial Tat translocation in vitro. EMBO J. 20:24722479.
215. Yeats, C.,, R. D. Finn,, and A. Bateman. 2002. The PASTA domain: a beta-lactam-binding domain. Trends Biochem. Sci. 27:438.