Chapter 44 : Mycobacterium tuberculosis Virulence and Evolution

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Mycobacterium tuberculosis Virulence and Evolution, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815639/9781555814144_Chap44-1.gif /docserver/preview/fulltext/10.1128/9781555815639/9781555814144_Chap44-2.gif


Tuberculosis (TB) was declared a global emergency by the World Health Organization in 1993, and the international scientific community is now making tremendous efforts to develop new antimycobacterial drugs and a new anti-TB vaccine, more effective than the Mycobacterium bovis BCG vaccine currently used in most parts of the world. Some actinobacteria form branching filaments resembling the mycelia of fungi and were originally classified as ''Actinomycetes.'' The future development of a new anti-TB vaccine, and of new antimycobacterial drugs, would probably benefit from a more detailed understanding of Mycobacterium tuberculosis virulence and evolution, including an explanation of how a bacterium that was probably initially saprophytic evolved to become a major, potentially lethal, microbial pathogen. Two single nucleotide polymorphisms (SNPs), in gyrA codon 95 and in katG codon 463, have been used to reconstruct the evolutionary history of the M. tuberculosis complex. The evolution of the M. tuberculosis complex thus appears to have been mostly clonal, with DNA duplications, inversions, and deletions. Restriction fragment length polymorphism studies take advantage of the presence in M. tuberculosis of insertion elements located at various positions in the genome in different strains. DNA fingerprinting techniques have been extensively used for clustering mycobacterial genotypes, studying M. tuberculosis transmission, characterizing outbreaks, and improving clinical management. Global searches for mycobacterial virulence genes have been carried out by screening libraries of M. tuberculosis mutants in mice and in macrophages, at both the cellular and the subcellular levels.

Citation: Neyrolles O, Gicquel B. 2008. Mycobacterium tuberculosis Virulence and Evolution, p 535-541. In Baquero F, Nombela C, Cassell G, Gutiérrez-Fuentes J (ed), Evolutionary Biology of Bacterial and Fungal Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815639.ch44
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1.
Figure 1.

Evolution of the M. tuberculosis complex. RD, region of difference; TbD, M. tuberculosis–specific deletion; katG, single nucleotide polymorphism (SNP) katG463 CTG (Leu)→CGG(Arg); gyrA, SNP gyrA95 ACC(Thr)→AGC(Ser). (Adapted from Marmiesse et al., 2004.)

Citation: Neyrolles O, Gicquel B. 2008. Mycobacterium tuberculosis Virulence and Evolution, p 535-541. In Baquero F, Nombela C, Cassell G, Gutiérrez-Fuentes J (ed), Evolutionary Biology of Bacterial and Fungal Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815639.ch44
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Anh, D. D.,, M. W. Borgdorff,, L. N. Van, et al. 2000. Mycobacterium tuberculosis Beijing genotype emerging in Vietnam. Emerg. Infect. Dis. 6: 302305.
2. Baker, L.,, T. Brown,, M. C. Maiden, and, F. Drobniewski. 2004. Silent nucleotide polymorphisms and a phylogeny for Mycobacterium tuberculosis. Emerg. Infect. Dis. 10: 15681577.
3. Behr, M. A.,, M. A. Wilson,, W. P. Gill, et al. 1999. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science 284: 15201523.
4. Berthet, F. X.,, M. Lagranderie,, P. Gounon, et al. 1998. Attenuation of virulence by disruption of the Mycobacterium tuberculosis erp gene. Science 282: 759762.
5. Bifani, P. J.,, B. Mathema,, N. E. Kurepina, and, B. N. Kreiswirth. 2002. Global dissemination of the Mycobacterium tuberculosis W-Beijing family strains. Trends Microbiol 10: 4552.
6. Bifani, P. J.,, B. B. Plikaytis,, V. Kapur, et al. 1996. Origin and interstate spread of a New York City multidrug-resistant Mycobacterium tuberculosis clone family. JAMA 275: 452457.
7. Blanc-Potard, A. B., and, B. Lafay. 2003. MgtC as a horizontally-acquired virulence factor of intracellular bacterial pathogens: evidence from molecular phylogeny and comparative genomics. J. Mol. Evol. 57: 479486.
8. Brosch, R.,, S. V. Gordon,, M. Marmiesse, et al. 2002. A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc. Natl. Acad. Sci. USA 99: 36843689.
9. Brosch, R.,, W. J. Philipp,, E. Stavropoulos,, M. J. Colston,, S. T. Cole, and, S. V. Gordon. 1999. Genomic analysis reveals variation between Mycobacterium tuberculosis H37Rv and the attenuated M. tuberculosis H37Ra strain. Infect. Immun. 67: 57685774.
10. Brudey, K.,, J. R. Driscoll,, L. Rigouts, et al. 2006. Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology. BMC Microbiol. 6: 23.
11. Camacho, L. R.,, P. Constant,, C. Raynaud, et al. 2001. Analysis of the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis. Evidence that this lipid is involved in the cell wall permeability barrier. J. Biol. Chem. 276: 1984519854.
12. 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: 257267.
13. Caminero, J. A.,, M. J. Pena,, M. I. Campos-Herrero, et al. 2001. Epidemiological evidence of the spread of a Mycobacterium tuberculosis strain of the Beijing genotype on Gran Canaria Island. Am. J. Respir. Crit. Care Med. 164: 11651170.
14. Chan, M. Y.,, M. Borgdorff,, C. W. Yip, et al. 2001. Seventy percent of the Mycobacterium tuberculosis isolates in Hong Kong represent the Beijing genotype. Epidemiol. Infect. 127: 169171.
15. Cole, S. T.,, R. Brosch,, J. Parkhill, et al. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393: 537544.
16. Drobniewski, F.,, Y. Balabanova,, V. Nikolayevsky, et al. 2005. Drug-resistant tuberculosis, clinical virulence, and the dominance of the Beijing strain family in Russia. JAMA 293: 27262731.
17. Drobniewski, F.,, Y. Balabanova,, M. Ruddy, et al. 2002. Rifampinand multidrug-resistant tuberculosis in Russian civilians and prison inmates: dominance of the Beijing strain family. Emerg. Infect. Dis. 8: 13201326.
18. Ebert, D. L., and, K. N. Olivier. 2002. Nontuberculous mycobacteria in the setting of cystic fibrosis. Clin. Chest. Med. 23: 655663.
19. Falush, D.,, T. Wirth,, B. Linz, et al. 2003. Traces of human migrations in Helicobacter pylori populations. Science 299: 15821585.
20. Filliol, I.,, J. R. Driscoll,, D. van Soolingen, et al. 2003. Snapshot of moving and expanding clones of Mycobacterium tuberculosis and their global distribution assessed by spoligotyping in an international study. J. Clin. Microbiol. 41: 19631970.
21. Filliol, I.,, A. S. Motiwala,, M. Cavatore, et al. 2006. Global phylogeny of Mycobacterium tuberculosis based on single nucleotide polymorphism (SNP) analysis: insights into tuberculosis evolution, phylogenetic accuracy of other DNA fingerprinting systems, and recommendations for a minimal standard SNP set. J. Bacteriol. 188: 759772.
22. Fine, P. E. 1989. The BCG story: lessons from the past and implications for the future. Rev. Infect. Dis. 11 (Suppl 2): S353S359.
23. Frieden, T. R.,, T. R. Sterling,, S. S. Munsiff,, C. J. Watt, and, C. Dye. 2003. Tuberculosis. Lancet 362: 887899.
24. Frothingham, R., and, W. A. Meeker-O’Connell. 1998. Genetic diversity in the Mycobacterium tuberculosis complex based on variable numbers of tandem DNA repeats. Microbiology 144: 11891196.
25. Gagneux, S.,, K. Deriemer,, T. Van, et al. 2006. Variable host-pathogen compatibility in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 103: 28692873.
26. Glynn, J. R.,, J. Whiteley,, P. J. Bifani,, K. Kremer, and, D. van Soolingen. 2002. Worldwide occurrence of Beijing/W strains of Mycobacterium tuberculosis: a systematic review. Emerg. Infect. Dis. 8: 843849.
27. Goguet de la Salmoniere, Y. O.,, C. C. Kim,, A. G. Tsolaki,, A. S. Pym,, M. S. Siegrist, and, P. M. Small. 2004. High-throughput method for detecting genomic-deletion polymorphisms. J. Clin. Microbiol. 42: 29132918.
28. 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: 643655.
29. Groenen, P. M.,, A. E. Bunschoten,, D. van Soolingen, and, J. D. van Embden. 1993. Nature of DNA polymorphism in the direct repeat cluster of Mycobacterium tuberculosis: application for strain differentiation by a novel typing method. Mol. Microbiol. 10: 10571065.
30. Gutacker, M. M.,, B. Mathema,, H. Soini, et al. 2006. Single-nucleotide polymorphism-based population genetic analysis of Mycobacterium tuberculosis strains from 4 geographic sites. J. Infect. Dis. 193: 121128.
31. Hensel, M.,, J. E. Shea,, C. Gleeson,, M. D. Jones,, E. Dalton, and, D. W. Holden. 1995. Simultaneous identification of bacterial virulence genes by negative selection. Science 269: 400403.
32. Jain, R.,, M. C. Rivera,, J. E. Moore, and, J. A. Lake. 2003. Horizontal gene transfer accelerates genome innovation and evolution. Mol. Biol. Evol. 20: 15981602.
33. Kapur, V.,, T. S. Whittam, and, J. M. Musser. 1994. Is Mycobacterium tuberculosis 15,000 years old? J. Infect. Dis. 170: 13481349.
34. Kaufmann, S. H. 2001. How can immunology contribute to the control of tuberculosis? Nat. Rev. Immunol. 1: 2030.
35. Kinsella, R. J.,, D. A. Fitzpatrick,, C. J. Creevey, and, J. O. McInerney. 2003. Fatty acid biosynthesis in Mycobacterium tuberculosis: lateral gene transfer, adaptive evolution, and gene duplication. Proc. Natl. Acad. Sci. USA 100: 1032010325.
36. Kruuner, A.,, S. E. Hoffner,, H. Sillastu, et al. 2001. Spread of drug-resistant pulmonary tuberculosis in Estonia. J. Clin. Microbiol. 39: 33393345.
37. Lopez, B.,, D. Aguilar,, H. Orozco, et al. 2003. A marked difference in pathogenesis and immune response induced by different Mycobacterium tuberculosis genotypes. Clin. Exp. Immunol. 133: 3037.
38. Manca, C.,, L. Tsenova,, C. E. Barry, 3rd, et al. 1999. Mycobacterium tuberculosis CDC1551 induces a more vigorous host response in vivo and in vitro, but is not more virulent than other clinical isolates. J. Immunol. 162: 67406746.
39. Manca, C.,, L. Tsenova,, A. Bergtold, et al. 2001. Virulence of a Mycobacterium 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. USA 98: 57525757.
40. Marmiesse, M.,, P. Brodin,, C. Buchrieser,, C. Gutierrez,, N. Simoes,, V. Vincent,, P. Glasen,, S. T. Cole, and, R. Brosch. 2004. Macroarray and bioinformatic analyses reveal mycobacterial ‘core’ genes, variation in the ESAT-6 gene family and new phylogenetic markers for the Mycobacterium tuberculosis complex. Microbiology 150: 483496.
41. Martin, C.,, J. Timm,, J. Rauzier,, R. Gomez-Lus,, J. Davies, and, B. Gicquel. 1990. Transposition of an antibiotic resistance element in mycobacteria. Nature 345: 739743.
42. Mendelson, M.,, S. Walters,, I. Smith, and, G. Kaplan. 2005. Strain-specific mycobacterial lipids and the stimulation of protective immunity to tuberculosis. Tuberculosis 85: 407413.
43. Mokrousov, I.,, H. M. Ly,, T. Otten, et al. 2005. Origin and primary dispersal of the Mycobacterium tuberculosis Beijing genotype: clues from human phylogeography. Genome Res. 15: 13571364.
44. Musser, J. M. 2001. Single nucleotide polymorphisms in Mycobacterium tuberculosis structural genes. Emerg. Infect. Dis. 7: 486488.
45. Niemann, S.,, S. Rusch-Gerdes,, M. L. Joloba, et al. 2002. Mycobacterium africanum subtype II is associated with two distinct genotypes and is a major cause of human tuberculosis in Kampala, Uganda. J. Clin. Microbiol. 40: 33983405.
46. Niobe-Eyangoh, S. N.,, C. Kuaban,, P. Sorlin, et al. 2003. Genetic biodiversity of Mycobacterium tuberculosis complex strains from patients with pulmonary tuberculosis in Cameroon. J. Clin. Microbiol. 41: 25472553.
47. Ochman, H.,, J. G. Lawrence, and, E. A. Groisman. 2000. Lateral gene transfer and the nature of bacterial innovation. Nature 405: 299304.
48. Otal, I.,, C. Martin,, V. Vincent-Levy-Frebault,, D. Thierry, and, B. Gicquel. 1991. Restriction fragment length polymorphism analysis using IS 6110 as an epidemiological marker in tuberculosis. J. Clin. Microbiol. 29: 12521254.
49. Parrish, N. M.,, J. D. Dick, and, W. R. Bishai. 1998. Mechanisms of latency in Mycobacterium tuberculosis. Trends Microbiol. 6: 107112.
50. 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: 1095510960.
51. Pelicic, V.,, J. M. Reyrat, and, B. Gicquel. 1996. Generation of unmarked directed mutations in mycobacteria, using sucrose counter-selectable suicide vectors. Mol. Microbiol. 20: 919925.
52. Pethe, K.,, D. L. Swenson,, S. Alonso,, J. Anderson,, C. Wang, and, D. G. Russell. 2004. Isolation of Mycobacterium tuberculosis mutants defective in the arrest of phagosome maturation. Proc. Natl. Acad. Sci. USA 101: 1364213647.
53. Pfyffer, G. E.,, A. Strassle,, T. van Gorkum, et al. 2001. Multidrug-resistant tuberculosis in prison inmates, Azerbaijan. Emerg. Infect. Dis. 7: 855861.
54. Philippe, H., and, C. J. Douady. 2003. Horizontal gene transfer and phylogenetics. Curr. Opin. Microbiol. 6: 498505.
55. Rad, M. E.,, P. Bifani,, C. Martin, et al. 2003. Mutations in putative mutator genes of Mycobacterium tuberculosis strains of the W-Beijing family. Emerg. Infect. Dis. 9: 838845.
56. Rosas-Magallanes, V.,, P. Deschavanne,, L. Quintana-Murci,, R. Brosch,, B. Gicquel, and, O. Neyrolles. 2006. Horizontal transfer of a virulence operon to the ancestor of Mycobacterium tuberculosis. Mol. Biol. Evol. 23: 11291135.
57. Rosas-Magallanes, V.,, G. Stadthagen,, J. Rauzier,, L. B. Barriero,, L. Tailleux,, F. Boudou,, R. Griffin,, J. Nigou,, M. Jackson,, B. Gicquel, and, O. Neyrolles. 2007 Signature-tagged transposon mutagenesis identifies novel Mycobacterium tuberculosis genes involved in the parasitism of human macrophages. Infect. Immun. 75: 504507.
58. Rousseau, C.,, N. Winter,, E. Pivert, et al. 2004. Production of phthiocerol dimycocerosates protects Mycobacterium tuberculosis from the cidal activity of reactive nitrogen intermediates produced by macrophages and modulates the early immune response to infection. Cell. Microbiol. 6: 277287.
59. 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.
60. Sassetti, C. M., and, E. J. Rubin. 2003. Genetic requirements for mycobacterial survival during infection. Proc. Natl. Acad. Sci. USA 100: 1298912994.
61. Sreevatsan, S.,, X. Pan,, K. E. Stockbauer, et al. 1997. Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination. Proc. Natl. Acad. Sci. USA 94: 98699874.
62. Stead, W. W.,, K. D. Eisenach,, M. D. Cave, et al. 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: 12671268.
63. Stewart, G. R.,, J. Patel,, B. D. Robertson,, A. Rae, and, D. B. Young. 2005. Mycobacterial mutants with defective control of phagosomal acidification. PLoS Pathog. 1: 269278.
64. Supply, P.,, E. Mazars,, S. Lesjean,, V. Vincent,, B. Gicquel, and, C. Locht. 2000. Variable human minisatellite-like regions in the Mycobacterium tuberculosis genome. Mol. Microbiol. 36: 762771.
65. Thierry, D.,, A. Brisson-Noel,, V. Vincent-Levy-Frebault,, S. Nguyen,, J. L. Guesdon, and, B. Gicquel. 1990a. Characterization of a Mycobacterium tuberculosis insertion sequence, IS 6110, and its application in diagnosis. J. Clin. Microbiol. 28: 26682673.
66. Thierry, D.,, M. D. Cave,, K. D. Eisenach, et al. 1990b. IS 6110, an IS-like element of Mycobacterium tuberculosis complex. Nucleic Acids Res. 18: 188.
67. Tsenova, L.,, E. Ellison,, R. Harbacheuski, et al. 2005. Virulence of selected Mycobacterium tuberculosis clinical isolates in the rabbit model of meningitis is dependent on phenolic glycolipid produced by the bacilli. J. Infect. Dis. 192: 98106.
68. van Crevel, R.,, R. H. Nelwan,, W. de Lenne, et al. 2001. Mycobacterium tuberculosis Beijing genotype strains associated with febrile response to treatment. Emerg. Infect. Dis. 7: 880883.
69. van Embden, J. D.,, M. D. Cave,, J. T. Crawford, et al. 1993. Strain identification of Mycobacterium tuberculosis by DNA finger-printing: recommendations for a standardized methodology. J. Clin. Microbiol. 31: 406409.
70. van Soolingen, D.,, L. Qian,, P. E. de Haas, et al. 1995. Predominance of a single genotype of Mycobacterium tuberculosis in countries of East Asia. J. Clin. Microbiol. 33: 32343238.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error