Concluding Remarks

The success of M. tuberculosis and other mycobacterial pathogens is undoubtedly a consequence of a finely tuned dialogue that has evolved over time between the pathogen and host. The availability of genome sequences from several mycobac-terial species has considerably enlarged our knowledge of these pathogens, and now makes it possible to explore their pathogenic lifecycle and evolution. This information will play a key role in the development of new therapeutic and preventive strategies to address the immense global burden of mycobacterial disease.


We are grateful to P. Brodin, C. Demangel, T. Garnier, T. Stinear, G. Hewinson, and S. T. Cole for advice and encouragement. This work was supported by the Association Française Raoul Follereau, the European Union (QLK2-CT-2001-02018), the Ministère de la Recherche et Nouvelles Technologies (ACI Microbiologie), and the Institut Pasteur (PTR 35, PTR 110, and GPH 5).


Andries K., P. Verhasselt, J. Guillemont,

H. W. Gohlmann, J. M. Neefs, H. Winkler, J. Van Gestel, P. Timmerman, M. Zhu, E. Lee, P. Williams, D. de Chaf-foy, E. Huitric, S. Hoffner, E. Cambau, C. Truffot-Pernot, N. Lounis and V. Jar-lier. 2005. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 307:223-227.

Anes, E., M. P. Kuhnel, E. Bos, J. Moniz-Pereira, A. Habermann, and G. Griffiths. 2003. Selected lipids activate phagosome actin assembly and maturation resulting in killing of pathogenic mycobacteria. Nat Cell Biol 5:793-802.

Behr, M. A., M. A. Wilson, W. P. Gill, H. Sal-amon, G. K. Schoolnik, S. Rane, and P. M. Small. 1999. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science 284:15201523.

Berthet, F. X., M. Lagranderie, P. Gounon, C. Laurent-Winter, D. Ensergueix, P. Chavarot, F. Thouron, E. Maranghi, V. Pelicic, D. Portnoi, G. Marchal, and B. Gicquel. 1998a. Attenuation of virulence by disruption of the Mycobacterium tuberculosis erp gene. Science 282:759-762.

Berthet, F. X., P. B. Rasmussen, I. Rosenk-rands , P. Andersen and B. Gicquel. 1998b. A Mycobacterium tuberculosis operon encoding ESAT-6 and a novel low-molecular-mass culture filtrate protein (CFP-10). Microbiology 144:31953203.

Boshoff,H. I., M. B. Reed, C. E. Barry, 3rd, and V. Mizrahi. 2003. DnaE2 polymer-ase contributes to in vivo survival and the emergence of drug resistance in

Mycobacterium tuberculosis. Cell 113:183-193.

Braunstein, M., S. S. Bardarov, and W. R. Jacobs, Jr. 2002. Genetic methods for deciphering virulence determinants of Mycobacterium tuberculosis. Methods Enzymol 358:67-99.

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.

Brennan, M. J., and G. Delogu. 2002. The PE multigene family: a 'molecular mantra' for mycobacteria. Trends Microbiol 10:246-249.

A. Billault, T. Garnier, S. Niemann, S. T. Cole, and R. Brosch. 2002. Bacterial artificial chromosome-based comparative genomic analysis identifies Mycobacter-ium microti as a natural ESAT-6 deletion mutant. Infect Immun 70:55685578.

Brodin P., L. Majlessi, R. Brosch, D. Smith, G. Bancroft, S. Clark, A. Williams, C. Leclerc and S. T. Cole. 2004. Enhanced protection against tuberculosis by vaccination with recombinant Mycobacterium microti vaccine that induces T cell immunity against region of difference 1 antigens. J Infect Dis. 190:115-122.

Brosch, R., S. V. Gordon, M. Marmiesse, P. Brodin, C. Buchrieser, K. Eiglmeier, T. Garnier, C. Gutierrez, G. Hewinson, K. Kremer, L. M. Parsons, A. S. Pym, S. Samper, D. van Soolingen, and S. T. Cole. 2002. A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc Natl Acad Sci USA 99:3684-3689. Brosch, R., A. S. Pym, S. V. Gordon, and S. T. Cole. 2001. The evolution of mycobacterial pathogenicity: clues from comparative genomics. Trends Microbiol 9:452-458. Buchmeier, N., A. Blanc-Potard, S. Ehrt, D. Piddington, L. Riley, and E. A. Grois-man. 2000. A parallel intraphagosomal survival strategy shared by mycobacter-ium tuberculosis and Salmonella enterica. Mol Microbiol 35:1375-1382. Camacho, L. R., D. Ensergueix, E. Perez,

B. Gicquel, and C. Guilhot. 1999. Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis. Mol Microbiol 34:257-267.

C. Churcher, D. Harris, S. V. Gordon, K. Eiglmeier, S. Gas, C. E. Barry, 3rd, 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, B. G. Barrell, and et al. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537-544.

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. Constant P., E. Perez, W. Malaga, M. A. Laneelle, O. Saurel, M. Daffe and Guilhot C. Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methly esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene. 2002. J Biol Chem 277:38148-38158. Cox, J. S., B. Chen, M. McNeil, and W. R. Jacobs, Jr. 1999. Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice. Nature 402:79-83. Dahl, J. L., C. N. Kraus, H. I. Boshoff,

C. E. Barry, 3rd. 2003. The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice. Proc Natl Acad Sci U S A 100:1002610031.

Dye, C., S. Scheele, P. Dolin, V. Pathania and M. C. Raviglione. 1999. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA.282:677-686. Fleischmann, R. D., D. Alland, J. A. Eisen, L. Carpenter, O. White, J. Peterson, R. DeBoy, R. Dodson, M. Gwinn,

D. Haft, E. Hickey, J. F. Kolonay, W. C. Nelson, L. A. Umayam, M. Ermolaeva, S. L. Salzberg, A. Delcher, T. Utterback, J. Weidman, H. Khouri, J. Gill,

A. Mikula, W. Bishai, W. R. Jacobs Jr., J. C. Venter, and C. M. Fraser. 2002. Whole-genome comparison of Mycobac-terium tuberculosis clinical and laboratory strains. J Bacteriol 184:5479-5490. Garnier, T., K. Eiglmeier, J. C. Camus, N. Medina, H. Mansoor, M. Pryor, S. Duthoy, S. Grondin, C. Lacroix, C. Monsempe, S. Simon, B. Harris, R. Atkin, J. Doggett, R. Mayes, L. Keating, P. R. Wheeler, J. Parkhill, B. G. Bar-rell, S. T. Cole, S. V. Gordon, and R. G. Hewinson. 2003. The complete genome sequence of Mycobacterium bovis. Proc Natl Acad Sci U S A 100:7877-7882. George K. M., D. Chatterjee, G. Gunawar-dana, D. Welty, T. Lee , and P.L. Small. 1999. Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence. Science 283: 854-857.

Glickman, M. S., J. S. Cox, and W. R. Jacobs, Jr. 2000. A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis. Mol Cell 5:717727.

Gordon, S. V., R. Brosch, A. Billault, T. Garnier, K. Eiglmeier, and S. T. Cole. 1999. Identification of variable regions in the genomes of tubercle bacilli using bacterial artificial chromosome arrays. Mol Microbiol 32:643-655.

Goren, M. B., P. D'Arcy Hart, M. R. Young, and J. A. Armstrong. 1976. Prevention ofphagosome-lysosome fusion in cultured macrophages by sulfatides of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 73:2510-2514.

Gutacker M. M., J. C. Smoot, C. A. Migliac-cio, S. M. Ricklefs, S. Hua , D. V. Cousins, E. A. Graviss, E. Shashkina, B. N. Kreiswirth and J. M. Musser. 2002. Genome-wide analysis of synonymous single nucleotide polymorphisms in Myco-bacterium tuberculosis complex organisms: resolution of genetic relationships among closely related microbial strains. Genetics. 162:1533-1543.

Gutierrez, M. C., Brisse, S., Brosch, R., Fabre, M., Omais, B., Marmiesse, M., Supply, P., and Vincent V. (2005) Ancient Origin and Gene Mosaicism of the Progenitor of Mycobacterium tuberculosis, PLoS Pathog 1: e5.

Guinn, K. I., M. J. Hickey, S. K. Mathur, K. L. Zakel, J. E. Grotzke, D. M. Lewinsohn, S. Smith, and D. R. Sherman. 2004. Individual RD1-region genes are required for export of ESAT-6/CFP-10 and for virulence of Mycobacterium tuberculosis. Mol Microbiol 51:359-370.

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

Hart, P. D., and I. Sutherland. 1977. BCG and vole bacillus vaccines in the prevention oftuberculosis in adolescence and early adult life. Br Med J 2:293-295.

Hingley-Wilson, S. M., V. K. Sambanda-murthy, and W. R. Jacobs, Jr. 2003. Sur vival perspectives from the world's most successful pathogen, Mycobacterium tuberculosis. Nat Immunol 4:949-955. Hondalus, M. K., S. Bardarov, R. Russell, J. Chan, W. R. Jacobs, Jr., and B. R. Bloom. 2000. Attenuation of and protection induced by a leucine auxotroph of Mycobacterium tuberculosis. Infect Immun 68:2888-2898. 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-Guerin is a loss of secreted lytic function required for invasion of lung interstitial tissue. Proc Natl Acad Sci U S A 100:12420-12425. Imaeda, T. (1985) Deoxyribonucleic acid relatedness among selected strains of Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium bovis BCG, Mycobacterium microti and Mycobacterium africanum. Int J Syst Bacteriol 35:147-150. Jackson, M., S. W. Phalen, M. Lagranderie,

D. Ensergueix, P. Chavarot, G. Marchal, D. N. McMurray, B. Gicquel, and

C. Guilhot. 1999. Persistence and protective efficacy of a Mycobacterium tuberculosis auxotroph vaccine. Infect Immun 67:2867-2873. Johnson PD, StinearT, Small PL, Pluschke G, Merritt RW, Portaels F, Huygen K, Hayman JA, Asiedu K. 2005. Buruli Ulcer (M.ulcerans infection): new insights, new hope for disease control. PLoS Med. 2:e108. Kaufmann, S. H. 2001. How can immunology contribute to the control of tuberculosis? Nat Rev Immunol 1:20-30. Kaushal, D., B. G. Schroeder, S. Tyagi, T. Yoshimatsu, C. Scott, C. Ko, L. Carpenter, J. Mehrotra, Y. C. Manabe, R. D. Fleischmann, and W. R. Bishai. 2002. Reduced immunopathology and mortality despite tissue persistence in a Myco-bacterium tuberculosis mutant lacking alternative sigma factor, SigH. Proc Natl Acad Sci U S A 99:8330-8335. Keating L. A. , P. R. Wheeler, H. Mansoor, J. K. Inwald, J. Dale, R. G. Hewinson and S. V. Gordon. 2005. The pyruvate requirement of some members of the Mycobacterium tuberculosis complex is due to an inactive pyruvate kinase: implications for in vivo growth. Mol Microbiol 2005 56:163-174. 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-Guerin attenuation. J Infect Dis 187:117-123. Lopez, B., D. Aguilar, H. Orozco, M. Burger,

C. Espitia, V. Ritacco, L. Barrera, K. Kremer, R. Hernandez-Pando, K. Huygen, and D. van Soolingen. 2003. A marked difference in pathogenesis and immune response induced by different Mycobacterium tuberculosis genotypes. Clin Exp Immunol 133:30-37.

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.

Manca, C., L. Tsenova, A. Bergtold, S. Freeman, M. Tovey, J. M. Musser, C. E. Barry, 3rd, V. H. Freedman, and G. Kaplan. 2001. Virulence of a Myco-bacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-alpha/beta. Proc Natl Acad Sci U S A 98:5752-5757. Marmiesse, M., P. Brodin, C. Buchrieser, C. Gutierrez, N. Simoes, V. Vincent, P. Glaser, S. T. Cole and R. Brosch 2004. Macro-array and bioinformatic analyses reveal mycobacterial 'core' genes, variation in the ESAT-6 gene family and new phylogenetic markers for the Mycobac-terium tuberculosis complex. Microbiology 150:483-496. Marsollier L., R. Robert, J. Aubry, J. S. Andre, H. Kouakou, P. Legras, A. L. Manceau, C. Mahaza and B. Carbon-nelle. 2002. Aquatic insects as a vector for Mycobacterium ulcerans. Appl Environ Microbiol 68: 4623-4628. Marsollier L., T. Severin, J. Aubry, R. W. Mer-ritt, J. P. Saint-Andre, P. Legras, A. L. Manceau, A. Chauty, B. Carbonnelle and S. T. Cole. 2004. Aquatic snails, pas sive hosts of Mycobacterium ulcerans. Appl Environ Microbiol 70:6296-6298. McKinney, J. D., K. Honer zu Bentrup, E. J. Munoz-Elias, A. Miczak, B. Chen, W. T. Chan, D. Swenson, J. C. Sacchettini, W. R. Jacobs, Jr., and D. G. Russell.

2000. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406:735-738.

Monot, M., Honore, N., Garnier, T., Araoz, R., Coppee, J. Y., Lacroix, C., Sow, S., Spencer, J. S., Truman, R. W., Williams, D. L., Gelber, R., Virmond, M., Flageul, B., Cho, S. N., Ji, B., Paniz-Mondolfi, A., Conivt, J., Young, S., Fine, P. E., Rasolofo, V., Brennan, P. J., and Cole, S. T. 2005. On the origin of leprosy. Science. 308:1040-1042. Mostowy, S., D. Cousins, J. Brinkman,

A. Aranaz, and M. A. Behr. 2002. Geno-mic deletions suggest a phylogeny for the Mycobacterium tuberculosis complex. J Infect Dis 186:74-80.

F. M. Collins, and W. R. Jacobs, Jr. 2003. Vaccine efficacy of a lysine auxotroph of Mycobacterium tuberculosis. Infect Immun 71:4190-4192. Pelicic, V., M. Jackson, J. M. Reyrat, W. R. Jacobs, Jr., B. Gicquel, and C. Guilhot. 1997. Efficient allelic exchange and transposon mutagenesis in Mycobacterium tuberculosis. Proc Natl Acad Sci USA 94:10955-10960. Perez E., P. Constant, A. Lemassu, F. Laval, M. Daffe and C. Guilhot. 2004. Characterization ofthree glycosyltransferases involved in the biosynthesis ofthe phenolic glycolipid antigens from the Myco-bacterium tuberculosis complex. J Biol Chem. 279:42574-42583. Perez, E., S. Samper, Y. Bordas, C. Guilhot,

B. Gicquel, and C. Martin. 2001. An essential role for phoP in Mycobacter-ium tuberculosis virulence. Mol Micro-biol 41:179-187.

Pethe, K., S. Alonso, F. Biet, G. Delogu, M. J. Brennan, C. Locht, and F. D. Menozzi.

2001. The heparin-binding haemagglu-tinin ofM. tuberculosis is required for extrapulmonary dissemination. Nature 412:190-194.

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.

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 9:533-9.

Raynaud, C., C. Guilhot, J. Rauzier, Y. Bordat, V. Pelicic, R. Manganelli, I. Smith, B. Gicquel, and M. Jackson. 2002. Phos-pholipases C are involved in the virulence of Mycobacterium tuberculosis. Mol Microbiol 45:203-217.

Reed M. B., P. Domenech, C. Manca, H. Su, A. K. Barczak, B. N. Kreiswirth, G. Kaplan and C. E. Barry 3rd. A glyco-lipid ofhypervirulent tuberculosis strains that inhibits the innate immune response. 2004. Nature 431:84-87.

Russell, D. G. 2001. Mycobacterium tuberculosis: here today, and here tomorrow. Nat Rev Mol Cell Biol 2:569-77.

Salamon, H., M. Kato-Maeda, P. M. Small, J. Drenkow, T. R. Gingeras. 2000. Detection of deleted genomic DNA using a semiautomated computational analysis of GeneChip data. Genome Res 10:2044-2054.

Sambandamurthy, V. K., X. Wang, B. Chen, R. G. Russell, S. Derrick, F. M. Collins, S. L. Morris, and W. R. Jacobs, Jr. 2002. A pantothenate auxotroph of Mycobacterium tuberculosis is highly attenuated and protects mice against tuberculosis. Nat Med 8:1171-1174.

Sassetti C. M., D. H. Boyd and E. J. Rubin. 2001. Comprehensive identification of conditionally essential genes in mycobacteria. Proc Natl Acad Sci USA 98:12712-12717.

Sassetti C. M., D. H. Boyd and E. J. Rubin. 2003. Genes required for mycobacterial growth defined by high density muta-genesis. Mol Microbiol. 48:77-84.

Sassetti C. M and E. J. Rubin. 2003. Genetic requirements for mycobacterial survival during infection. Proc Natl Acad Sci USA. 100:12989-12994.

Smith, C. V., and J. C. Sacchettini. 2003. Mycobacterium tuberculosis: a model system for structural genomics. Curr Opin Struct Biol 13:658-664.

Smith, D. A., T. Parish, N. G. Stoker, and G. J. Bancroft. 2001. Characterization of auxotrophic mutants of Mycobacterium tuberculosis and their potential as vaccine candidates. Infect Immun 69:1142-1150.

P. Andersen, and A. B. Andersen. 1995. Purification and characterization of a low-molecular-mass T-cell antigen secreted by Mycobacterium tuberculosis. Infect Immun 63:1710-1717.

Sreevatsan S, X. Pan, K. E. Stockbauer, N. D. Connell, B. N. Kreiswirth, T. S. Whittam and J. M. Musser. 1997. Restricted structural gene polymorphism in the Myco-bacterium tuberculosis complex indicates evolutionarily recent global dissemination. Proc Natl Acad Sci USA 94:9869-9874.

Stanley, S. A., S. Raghavan, W. W. Hwang, and J. S. Cox. 2003. Acute infection and macrophage subversion by Mycobacter-ium tuberculosis require a specialized secretion system. Proc Natl Acad Sci USA 100:13001-13006.

Stead, W. W., K. D. Eisenach, M. D. Cave, M. L. Beggs, G. L. Templeton, C. O. Thoen, and J. H. Bates. 1995. When did Mycobacterium tuberculosis infection first occur in the New World? An important question with public health implications. Am J Respir Crit Care Med 151:1267-1268.

Stermann M., L. Sedlacek , S. Maass and F. C. Bange. 2004. A promoter mutation causes differential nitrate reductase activity of Mycobacterium tuberculosis and Mycobacterium bovis. J Bacteriol 186:2856-2861.

Stewart, G. R., V. A. Snewin, G. Walzl, T. Hussell, P. Tormay, P. O'Gaora, M. Goyal, J. Betts, I. N. Brown, and D. B. Young. 2001. Overexpression ofheat-shock proteins reduces survival of Mycobacterium tuberculosis in the chronic phase of infection. Nat Med 7:732-737.

Steyn, A. J., D. M. Collins, M. K. Hondalus, W. R. Jacobs, Jr., R. P. Kawakami, and

B. R. Bloom. 2002. Mycobacterium tuberculosis WhiB3 interacts with RpoV to affect host survival but is dispensable for in vivo growth. Proc Natl Acad Sci USA 99:3147-3152.

Stinear T. P., A. Mve-Obiang, P. L. C. Small, W. Frigui, M. J. Pryor, R. Brosch, G. A. Jenkin, P. D. Johnson, J. K. Davies, R. E. Lee, S. Adusumilli, T. Garnier, S. F. Haydock, P. F. Leadlay and S. T. Cole. 2004. Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans. Proc Natl Acad Sci U S A 101:1345-1349.

Stinear T. P., H. Hong, W. Frigui, M. J. Pryor, R. Brosch, T. Garnier, P. F. Leadlay and S. T. Cole. 2005. Common evolutionary origin for the unstable virulence plasmid pMUM found in geographically diverse strains of Mycobacterium ulcerans. J Bacteriol 187:1668-1676.

Sula, L., and I. Radkovsky. 1976. Protective effects of M. microti vaccine against tuberculosis. J Hyg Epidemiol Microbiol Immunol 20:1-6.

Trivedi O. A., P. Arora, V. Sridharan, R. Tickoo, D. Mohanty and R.S. Gokhale. 2004. Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria. Nature 428:441-445.

Trivedi O. A., P. Arora, A. Vats, M. Z. Ansari, R. Tickoo , V. Sridharan, D. Mohanty and R.S. Gokhale. 2005. Dissecting the mechanism and assembly of a complex virulence mycobacterial lipid. Mol Cell 17:631-643.

Tullius, M. V., G. Harth, and M. A. Horwitz. 2003. Glutamine synthetase GlnA1 is essential for growth of Mycobacterium tuberculosis in human THP-1 macrophages and guinea pigs. Infect Immun 71:3927-3936.

van Soolingen, D., T. Hoogenboezem, P. E. de Haas, P. W. Hermans, M. A. Koe-dam, K. S. Teppema, P. J. Brennan, G. S. Besra, F. Portaels, J. Top, L. M. Schouls and J. D. van Embden. 1997. A novel pathogenic taxon ofthe Mycobacterium tuberculosis complex, Canetti: characterization of an exceptional isolate from Africa. Int J Syst Bacteriol 47:12361245.

Vergne I, J. Chua, H. H. Lee, M. Lucas, J. Belisle and V. Deretic. 2005. Mechanism ofphagolysosome biogenesis block by viable Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 102:4033-4038.

Walburger A, A. Koul, G. Ferrari, L. Nguyen, C. Prescianotto-Baschong, K. Huygen, B. Klebl, C. Thompson, G. Bacher and J. Pieters. 2004. Protein kinase G from pathogenic mycobacteria promotes survival within macrophages. Science 304:1800-1804.

Wayne L. G. and L. G. Hayes. 1996. An in vitro model for sequential study of shift-down of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infect Immun 64:20622069.

Weber I., C. Fritz, S. Ruttkowski, A. Kreft and F. C. Bange. 2000. Anaerobic nitrate reductase (narGHJI) activity of Mycobacterium bovis BCG in vitro and its contribution to virulence in immu-nodeficient mice. Mol Microbiol. 35:1017-1025.

0 0

Post a comment