Chapter 16 : Mycobacterial Evolution: Insights from Genomics and Population Genetics

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

Preview this chapter:
Zoom in

Mycobacterial Evolution: Insights from Genomics and Population Genetics, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815622/9781555813000_Chap16-1.gif /docserver/preview/fulltext/10.1128/9781555815622/9781555813000_Chap16-2.gif


is an obligate human pathogen that is transmitted by aerosol from patients with pulmonary tuberculosis. Until recently, the evolution of tuberculosis remained largely in the realms of speculation. However, the genomics revolution has had the same dramatic effect on the study of as it has had on the study of other bacterial pathogens. This chapter has been structured around the different genetic approaches that are providing insights into the evolution of and have specifically emphasized important new findings emerging from recent studies of population genetics. A more complete understanding of the evolution of pathogenic mycobacteria will ultimately require definition of the genomic changes that accompanied the transition to a pathogenic lifestyle. One of the most significant genetic observations with relevance to understanding the evolution of has been the lack of single nucleotide polymorphisms (SNPs) detected among clinical isolates of . Recently, phylogenies based on large sequence polymorphisms (LSPs) or SNPs have confirmed that is deeply branched from the other complex members. Until recently, however, there was little formal effort to understand from an evolutionary perspective. Recent advances in genomics now make it possible to explore the evolution of .

Citation: Pym A, Small P. 2006. Mycobacterial Evolution: Insights from Genomics and Population Genetics, p 301-325. In Seifert H, DiRita V (ed), Evolution of Microbial Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815622.ch16
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Phylogeny of slow-growing based on 16S rRNA sequences (adapted from reference ). Phylogenetic distances are not precise. Species that are underlined correspond to the obligate human pathogens. The complex corresponds to , and , which have identical 16S rRNA sequences.

Citation: Pym A, Small P. 2006. Mycobacterial Evolution: Insights from Genomics and Population Genetics, p 301-325. In Seifert H, DiRita V (ed), Evolution of Microbial Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815622.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Large sequence polymorphisms in the epoxide hydrolase locus of three complex strains. The large rectangular boxes correspond to the DNA fragment absent from each strain, with the precise H37Rv genome coordinates marking the extent of each deletion. Deletions 236 and 236A were detected in strains isolated from San Francisco, and RD8 was originally detected in BCG strains ( ). The distinct end points for each polymorphism indicate that these genomic deletions have occurred independently. The annotation is according to the H37Rv sequence ( ): Rv 3618, function unknown; , epoxide hydrolase; and , members of the early secretory antigen family; PPE65 and PE32, members of two large gene families of unknown function; , lipoprotein; and , involved in purine salvage.

Citation: Pym A, Small P. 2006. Mycobacterial Evolution: Insights from Genomics and Population Genetics, p 301-325. In Seifert H, DiRita V (ed), Evolution of Microbial Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815622.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Phylogeographical structure of reactivating strains in San Francisco. The phylogeny was constructed by maximum parsimony using large sequence polymorphisms detected by microarray analysis. The place of birth of the source case for each strain is shown on the right. White, crossed, black, and lined shadings have been superimposed, corresponding to East Asia, the Philippines, the Americas, or other places of birth, to reveal distinct geographical clades.

Citation: Pym A, Small P. 2006. Mycobacterial Evolution: Insights from Genomics and Population Genetics, p 301-325. In Seifert H, DiRita V (ed), Evolution of Microbial Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815622.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Achtman, M.,, K. Zurth,, G. Morelli,, G. Torrea,, A. Guiyoule, and, E. Carniel. 1999. Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis. Proc. Natl. Acad. Sci. USA 96: 1404314048.
2. Alm, R. A.,, L. S. Ling,, D. T. Moir,, B. L. King,, E. D. Brown,, P. C. Doig,, D. R. Smith,, B. Noonan,, B. C. Guild,, B. L. deJonge,, G. Carmel,, P. J. Tummino,, A. Caruso,, M. Uria-Nickelsen,, D. M. Mills,, C. Ives,, R. Gibson,, D. Merberg,, S. D. Mills,, Q. Jiang,, D. E. Taylor,, G. F. Vovis, and, T. J. Trust. 1999. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397: 176180.
3. Andersson,, S. G.,, A. Zomorodipour,, J. O. Andersson,, T. Sicheritz-Ponten,, U. C. Alsmark,, R. M. Podowski,, A. K. Naslund,, A. S. Eriksson,, H. H. Winkler, and, C. G. Kurland. 1998. The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 396: 133140.
4. 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.
5. Barker, L. P.,, K. M. George,, S. Falkow, and, P. L. Small. 1997. Differential trafficking of live and dead Mycobacterium marinum organisms in macrophages. Infect. Immun. 65: 14971504.
6. Barry, C. E., III. 2001. Interpreting cell wall ‘virulence factors’ of Mycobacterium tuberculosis. Trends Microbiol. 9: 237241.
7. 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.
8. Bentley,, S. D.,, K. F. Chater,, A. M. Cerdeno Tarraga,, G. L. Challis,, N. R. Thomson,, K. D. James,, D. E. Harris,, M. A. Quail,, H. Kieser,, D. Harper,, A. Bateman,, S. Brown,, G. Chandra,, C. W. Chen,, M. Collins,, A. Cronin,, A. Fraser,, A. Goble,, J. Hidalgo,, T. Hornsby,, S. Howarth,, C. H. Huang,, T. Kieser,, L. Larke,, L. Murphy,, K. Oliver,, S. O’Neil,, E. Rabbinowitsch,, M. A. Rajandream,, K. Rutherford,, S. Rutter,, K. Seeger,, D. Saunders,, S. Sharp,, R. Squares,, S. Squares,, K. Taylor,, T. Warren,, A. Wietzorrek,, J. Woodward,, B. G. Barrell,, J. Parkhill, and, D. A. Hopwood. 2002. Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 417: 141147.
9. 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. 1998. Attenuation of virulence by disruption of the Mycobacterium tuberculosis erp gene. Science 282: 759762.
10. 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 Myco-bacterium tuberculosis strain H37Rv with clinical isolate CDC 1551. Microbiology 146 (Pt. 12): 32053216.
11. Bibb,, L. A., and, G. F. Hatfull. 2002. Integration and excision of the Mycobacterium tuberculosis prophage-like element, phiRv1. Mol. Microbiol. 45: 15151526.
12. 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.
13. Billington,, O. J.,, T. D. McHugh, and, S. H. Gillespie. 1999. Physiological cost of rifampin resistance induced in vitro in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 43: 18661869.
14. Borgdorff,, M. W.,, M. A. Behr,, N. J. Nagelkerke,, P. C. Hopewell, and, P. M. Small. 2000. Transmission of tuberculosis in San Francisco and its association with immigration and ethnicity. Int. J. Tuberc. Lung Dis. 4: 287294.
15. Boshoff,, H. I.,, M. B. Reed, C. E. Barry III, and, V. Mizrahi. 2003. DnaE2 polymerase contributes to in vivo survival and the emergence of drug resistance in Mycobacterium tuberculosis. Cell 113: 183193.
16. Braden,, C. R.,, G. P. Morlock,, C. L. Woodley,, K. R. Johnson,, A. C. Colombel,, M. D. Cave,, Z. Yang,, S. E. Valway,, I. M. Onorato, and, J. T. Crawford. 2001. Simultaneous infection with multiple strains of Mycobacterium tuberculosis. Clin. Infect. Dis. 33: e42e47.
17. Braunstein,, M.,, B. J. Espinosa,, J. Chan,, J. T. Belisle, and, R. W. Jacobs, Jr. 2003. SecA2 functions in the secretion of superoxide dismutase A and in the virulence of Mycobacterium tuberculosis. Mol. Microbiol. 48: 453464.
18. 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.
19. Brodin,, P.,, K. Eiglmeier,, M. Marmiesse,, A. Billault,, T. Garnier,, S. Niemann,, S. T. Cole, and, R. Brosch. 2002. Bacterial artificial chromosome-based comparative genomic analysis identifies Mycobacterium microti as a natural ESAT-6 deletion mutant. Infect. Immun. 70: 55685578.
20. Brosch,, R.,, S. V. Gordon,, A. Billault,, T. Garnier,, K. Eiglmeier,, C. Soravito,, B. G. Barrell, and, S. T. Cole. 1998. Use of a Mycobacterium tuberculosis H37Rv bacterial artificial chromosome library for genome mapping, sequencing, and comparative genomics. Infect. Immun. 66: 22212229.
21. 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: 36843689.
22. 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.
23. 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: 452458.
24. Buchmeier,, N.,, A. Blanc-Potard,, S. Ehrt,, D. Piddington,, L. Riley, and, E. A. Groisman. 2000. A parallel intraphagosomal survival strategy shared by Mycobacterium tuberculosis and Salmonella enterica. Mol. Microbiol. 35: 13751382.
25. Burgos,, M. V., and, A. S. Pym. 2002. Molecular epidemiology of tuberculosis. Eur. Respir. J. Suppl. 36: 54s65s.
26. 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.
27. 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.
28. Cavanagh,, R.,, M. Begon,, M. Bennett,, T. Ergon,, I. M. Graham,, P. E. De Haas,, C. A. Hart,, M. Koedam,, K. Kremer,, X. Lambin,, P. Roholl, and, D. van Soolingen. 2002. Mycobacterium microti infection (vole tuberculosis) in wild rodent populations. J. Clin. Microbiol. 40: 32813285.
29. Chaves,, F.,, F. Dronda,, M. Alonso-Sanz, and, A. R. Noriega. 1999. Evidence of exogenous reinfection and mixed infection with more than one strain of Mycobacterium tuberculosis among Spanish HIV-infected inmates. AIDS 13: 615620.
30. Chen,, P.,, R. E. Ruiz,, Q. Li,, R. F. Silver, and, W. R. Bishai. 2000. Construction and characterization of a Mycobacterium tuberculosis mutant lacking the alternate sigma factor gene, sigF. Infect. Immun. 68: 55755580.
31. Cirillo,, J. D.,, S. Falkow,, L. S. Tompkins, and, L. E. Bermudez. 1997. Interaction of Mycobacterium avium with environmental amoebae enhances virulence. Infect. Immun. 65: 37593767.
32. Clemens,, D. L., and, M. A. Horwitz. 1995. Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited. J. Exp. Med. 181: 257270.
33. 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,, A. 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.
34. 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.
35. Coleman,, J. D., and, M. M. Cooke. 2001. Mycobacterium bovis infection in wildlife in New Zealand. Tuberculosis (Edinburgh) 81: 191202.
36. Collins,, D. M.,, R. P. Kawakami,, G. W. de Lisle,, L. Pascopella,, B. R. Bloom, and, W. R. Jacobs. 1995. Mutation of the principal sigma factor causes loss of virulence in a strain of the Mycobacterium tuberculosis complex. Proc. Natl. Acad. Sci. USA 92: 80368040.
37. Cox,, E. C. 1976. Bacterial mutator genes and the control of spontaneous mutation. Annu. Rev. Genet. 10: 135156.
38. 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: 7983.
39. Daffe,, M.,, M. McNeil, and, P. J. Brennan. 1991. Novel type-specific lipooligosaccharides from Mycobacterium tuberculosis. Biochemistry 30: 378388.
40. David,, H., and, C. M. Newman. 1971. Some observations on the genetics of isoniazid resistance in the tubercle bacilli. Am. Rev. Respir. Dis. 104: 508515.
41. David,, H. L. 1970. Probability distribution of drug-resistant mutants in unselected populations of Mycobacterium tuberculosis. Appl. Microbiol. 20: 810814.
42. Delogu, G., and, M. J. Brennan. 2001. Comparative immune response to PE and PE-PGRS antigens of Mycobacterium tuberculosis. Infect. Immun. 69: 56065611.
43. Dorrell,, N.,, J. A. Mangan,, K. G. Laing,, J. Hinds,, D. Linton,, H. Al-Ghusein,, B. G. Barrell,, J. Parkhill,, N. G. Stoker,, A. V. Karlyshev,, P. D. Butcher, and, B. W. Wren. 2001. Whole genome comparison of Campylobacter jejuni human isolates using a low-cost microarray reveals extensive genetic diversity. Genome Res. 11: 17061715.
44. Douglas,, J. T.,, L. Qian,, J. C. Montoya,, J. M. Musser,, J. D. van Embden,, D. van Soolingen, and, K. Kremer. 2003. Characterization of the Manila family of Mycobacterium tuberculosis. J. Clin. Microbiol. 41: 27232726.
45. 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: 677686.
46. Falush, D.,, T. Wirth,, B. Linz,, J. K. Pritchard,, M. Stephens,, M. Kidd,, M. J. Blaser,, D. Y. Graham,, S. Vacher,, G. I. Perez-Perez,, Y. Yamaoka,, F. Megraud,, K. Otto,, U. Reichard,, E. Katzowitsch,, X. Wang,, M. Achtman, and, S. Suerbaum. 2003. Traces of human migrations in Helicobacter pylori populations. Science 299: 15821585.
47. Fitzgerald,, J. R., and, J. M. Musser. 2001. Evolutionary genomics of pathogenic bacteria. Trends Microbiol. 9: 547553.
48. Fitzgerald,, J. R.,, D. E. Sturdevant,, S. M. Mackie,, S. R. Gill, and, J. M. Musser. 2001. Evolutionary genomics of Staphylococcus aureus: insights into the origin of methicillin-resistant strains and the toxic shock syndrome epidemic. Proc. Natl. Acad. Sci. USA 98: 88218826.
49. 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 Mycobacterium tuberculosis clinical and laboratory strains. J. Bacteriol. 184: 54795490.
50. Foster,, P. L. 1999. Mechanisms of stationary phase mutation: a decade of adaptive mutation. Annu. Rev. Genet. 33: 5788.
51. Frothingham, R.,, P. L. Strickland,, G. Bretzel,, S. Ramaswamy,, J. M. Musser, and, D. L. Williams. 1999. Phenotypic and genotypic characterization of Mycobacterium africanum isolates from West Africa. J. Clin. Microbiol. 37: 19211926.
52. Gamieldien,, J.,, A. Ptitsyn, and, W. Hide. 2002. Eukaryotic genes in Mycobacterium tuberculosis could have a role in pathogenesis and immuno-modulation. Trends Genet. 18: 58.
53. Garcia de Viedma,, D.,, M. Marin,, M. J. Ruiz Serrano,, L. Alcala, and, E. Bouza. 2003. Polyclonal and compartmentalized infection by Mycobacterium tuberculosis in patients with both respiratory and extrarespiratory involvement. J. Infect. Dis. 187: 695699.
54. 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. Barrell,, S. T. Cole,, S. V. Gordon, and, R. G. Hewinson. 2003. The complete genome sequence of Mycobacterium bovis. Proc. Natl. Acad. Sci. USA 100: 78777882.
55. Gil,, R.,, B. Sabater-Munoz,, A. Latorre,, F. J. Silva, and, A. Moya. 2002. Extreme genome reduction in Buchnera spp.: toward the minimal genome needed for symbiotic life. Proc. Natl. Acad. Sci. USA 99: 44544458.
56. Glickman,, M. S.,, J. S. Cox, and, W. R. Jacobs, Jr. 2000. A novel mycolic acid cyclopropane synthetase is required for coding, persistence, and virulence of Mycobacterium tuberculosis. Mol. Cell 5: 717727.
57. 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.
58. Goh,, K. S.,, E. Legrand,, C. Sola, and, N. Rastogi. 2001. Rapid differentiation of “Myco-bacterium canettii” from other Mycobacterium tuberculosis complex organisms by PCR-restriction analysis of the hsp65 gene. J. Clin. Microbiol. 39: 37053708.
59. 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.
60. Gordon,, S. V.,, B. Heym,, J. Parkhill,, B. Barrell, and, S. T. Cole. 1999. New insertion sequences and a novel repeated sequence in the genome of Mycobacterium tuberculosis H37Rv. Microbiology 145 (Pt. 4): 881892.
61. 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.
62. Gutacker, M. M.,, J. C. Smoot,, C. A. Migliaccio,, 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 Mycobacterium tuberculosis complex organisms. Resolution of genetic relationships among closely related microbial strains. Genetics 162: 15331543.
63. Harb,, O. S.,, L. Y. Gao, and, Y. Abu Kwaik. 2000. From protozoa to mammalian cells: a new paradigm in the life cycle of intracellular bacterial pathogens. Environ. Microbiol. 2: 251265.
64. Hendrix,, R. W.,, M. C. Smith,, R. N. Burns,, M. E. Ford, and, G. F. Hatfull. 1999. Evolutionary relationships among diverse bacteriophages and prophages: all the world’s a phage. Proc. Natl. Acad. Sci. USA 96: 21922197.
65. Hirsh,, A. E.,, A. G. Tsolaki,, K. DeRiemer,, M. W. Feldman, and, P. M. Small. 2004. Stable association between strains of Mycobacterium tuberculosis and their human host populations. Proc. Natl. Acad. Sci. USA 101: 48714876.
66. Ho,, T. B.,, B. D. Robertson,, G. M. Taylor,, R. J. Shaw, and, D. B. Young. 2000. Comparison of Mycobacterium tuberculosis genomes reveals frequent deletions in a 20 kb variable region in clinical isolates. Yeast 17: 272282.
67. Hou,, J. Y.,, J. E. Graham, and, J. E. Clark-Curtiss. 2002. Mycobacterium avium genes expressed during growth in human macrophages detected by selective capture of transcribed sequences (SCOTS). Infect. Immun. 70: 37143726.
68. Hughes,, A. L.,, R. Friedman, and, M. Murray. 2002. Genome wide pattern of synonymous nucleotide substitution in two complete genomes of Mycobacterium tuberculosis. Emerg. Infect. Dis 8: 13421346.
69. Johnsson,, K., and, P. G. Schultz. 1994. Mechanistic studies of the oxidation of isoniazid by the catalase peroxidase from Mycobacterium tuberculosis. J. Am. Chem. Soc. 116: 74257426.
70. Jordan,, I. K.,, I. B. Rogozin,, Y. I. Wolf, and, E. V. Koonin. 2002. Microevolutionary genomics of bacteria. Theor. Popul. Biol. 61: 435447.
71. Joyce,, E. A.,, K. Chan,, N. R. Salama, and, S. Falkow. 2002. Redefining bacterial populations: a post-genomic reformation. Nat. Rev. Genet. 3: 462473.
72. Kapur,, V.,, T. S. Whittam, and, J. M. Musser. 1994. Is Mycobacterium tuberculosis 15,000 years old? J. Infect. Dis. 170: 13481349.
73. Karunakaran,, P., and, J. Davies. 2000. Genetic antagonism and hypermutability in Mycobacterium smegmatis. J. Bacteriol. 182: 33313335.
74. Kato-Maeda,, M.,, J. T. Rhee,, T. R. Gingeras,, H. Salamon,, J. Drenkow,, N. Smittipat, and, P. M. Small. 2001. Comparing genomes within the species Mycobacterium tuberculosis. Genome Res. 11: 547554.
75. 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 immuno-pathology and mortality despite tissue persistence in a Mycobacterium tuberculosis mutant lacking alternative sigma factor, SigH. Proc. Natl. Acad. Sci. USA 99: 83308335.
76. 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.
77. Kremer,, K.,, D. van Soolingen,, R. Frothingham,, W. H. Haas,, P. W. Hermans,, C. Martin,, P. Palittapongarnpim,, B. B. Plikaytis,, L. W. Riley,, M. A. Yakrus,, J. M. Musser, and, J. D. van Embden. 1999. Comparison of methods based on different molecular epidemiological markers for typing of Mycobacterium tuberculosis complex strains: interlaboratory study of discriminatory power and reproducibility. J. Clin. Microbiol. 37: 26072618.
78. Lawrence,, J. G., and, H. Ochman. 1998. Molecular archaeology of the Escherichia coli genome. Proc. Natl. Acad. Sci. USA 95: 94139417.
79. LeClerc, J. E.,, B. Li,, W. L. Payne, and, T. A. Cebula. 1996. High mutation frequencies among Escherichia coli and Salmonella pathogens. Science 274: 12081211.
80. Li,, Q.,, C. C. Whalen,, J. M. Albert,, R. Larkin,, L. Zukowski,, M. D. Cave, and, R. F. Silver. 2002. Differences in rate and variability of intracellular growth of a panel of Mycobacterium tuberculosis clinical isolates within a human monocyte model. Infect. Immun. 70: 64896493.
81. Li,, Z.,, C. Kelley,, F. Collins,, D. Rouse, and, S. Morris. 1998. Expression of katG in Mycobacterium tuberculosis is associated with its growth and persistence in mice and guinea pigs. J. Infect. Dis. 177: 10301035.
82. 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.
83. Maiden,, M. C.,, J. A. Bygraves,, E. Feil,, G. Morelli,, J. E. Russell,, R. Urwin,, Q. Zhang,, J. Zhou,, K. Zurth,, D. A. Caugant,, I. M. Feavers,, M. Achtman, and, B. G. Spratt. 1998. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc. Natl. Acad. Sci. USA 95: 31403145.
84. Manabe,, Y. C., and, W. R. Bishai. 2000. Latent Mycobacterium tuberculosis—persistence, patience, and winning by waiting. Nat. Med. 6: 13271329.
85. Manca, C.,, L. Tsenova,, C. E. Barry III,, A. Bergtold,, S. Freeman,, P. A. Haslett,, J. M. Musser,, V. H. Freedman, and, G. Kaplan. 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.
86. Manca,, C.,, L. Tsenova,, A. Bergtold,, S. Freeman,, M. Tovey,, J. M. Musser,, C. E. Barry III,, V. H. Freedman, and, G. Kaplan. 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.
87. Maurelli,, A. T.,, R. E. Fernandez,, C. A. Bloch,, C. K. Rode, and, A. Fasano. 1998. “Black holes” and bacterial pathogenicity: a large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli. Proc. Natl. Acad. Sci. USA 95: 39433948.
88. Mazars,, E.,, S. Lesjean,, A. L. Banuls,, M. Gilbert,, V. Vincent,, B. Gicquel,, M. Tibayrenc,, C. Locht, and, P. Supply. 2001. High-resolution minisatellite-based typing as a portable approach to global analysis of Mycobacterium tuberculosis molecular epidemiology. Proc. Natl. Acad. Sci. USA 98: 19011906.
89. 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: 735738.
90. Menendez, M. C.,, M. J. Garcia,, M. C. Navarro,, J. A. Gonzalez-y-Merchand,, S. Rivera-Gutierrez,, L. Garcia-Sanchez, and, R. A. Cox. 2002. Characterization of an rRNA operon (rrnB) of Mycobacterium fortuitum and other mycobacterial species: implications for the classification of mycobacteria. J. Bacteriol. 184: 10781088.
91. Miltgen,, J.,, M. Morillon,, J. L. Koeck,, A. Varnerot,, J. F. Briant,, G. Nguyen,, D. Verrot,, D. Bonnet, and, V. Vincent. 2002. Two cases of pulmonary tuberculosis caused by Mycobacterium tuberculosis subsp canetti. Emerg. Infect. Dis. 8: 13501352.
92. Miltner,, E. C., and, L. E. Bermudez. 2000. Mycobacterium avium grown in Acanthamoeba castellanii is protected from the effects of antimicrobials. Antimicrob. Agents Chemother. 44: 19901994.
93. Mitchison,, D. A.,, J. G. Wallace,, A. L. Bhatia,, J. B. Selkon,, T. V. Subbaiah, and, M. C. Lancaster. 1960. A comparison of the virulence in Guinea-pigs of South Indian and British tubercle bacilli. Tubercle 41: 122.
94. Mizrahi,, V., and, S. J. Andersen. 1998. DNA repair in Mycobacterium tuberculosis. What have we learnt from the genome sequence? Mol. Microbiol. 29: 13311339.
95. Mizrahi,, V.,, S. S. Dawes, and, H. Rubin. 2000. DNA replication, p. 159–172. In G. F. Hatfull and, W. R. Jacobs (ed.), Molecular Genetics of Mycobacteria. ASM Press, Washington, D. C.
96. Moran,, N. A. 1996. Accelerated evolution and Muller’s rachet in endosymbiotic bacteria. Proc. Natl. Acad. Sci. USA 93: 28732878.
97. Mostowy, S.,, D. Cousins,, J. Brinkman,, A. Aranaz, and, M. A. Behr. 2002. Genomic deletions suggest a phylogeny for the Mycobacterium tuberculosis complex. J. Infect. Dis. 186: 7480.
98. Mukamolova,, G. V.,, O. A. Turapov,, D. I. Young,, A. S. Kaprelyants,, D. B. Kell, and, M. Young. 2002. A family of autocrine growth factors in Mycobacterium tuberculosis. Mol. Microbiol. 46: 623635.
99. Musser,, J. M.,, A. Amin, and, S. Ramaswamy. 2000. Negligible genetic diversity of Mycobacterium tuberculosis host immune system protein targets: evidence of limited selective pressure. Genetics 155: 716.
100. Nguyen,, D.,, P. Brassard,, J. Westley,, L. Thibert,, M. Proulx,, K. Henry,, K. Schwartzman,, D. Menzies, and, M. A. Behr. 2003. Widespread pyrazinamide-resistant Myco-bacterium tuberculosis family in a low-incidence setting. J. Clin. Microbiol. 41: 28782883.
101. Niobe-Eyangoh,, S. N.,, C. Kuaban,, P. Sorlin,, P. Cunin,, J. Thonnon,, C. Sola,, N. Rastogi,, V. Vincent, and, M. C. Gutierrez. 2003. Genetic biodiversity of Mycobacterium tuberculosis complex strains from patients with pulmonary tuberculosis in Cameroon. J. Clin. Microbiol. 41: 25472553.
102. Ochman,, H.,, S. Elwyn, and, N. A. Moran. 1999. Calibrating bacterial evolution. Proc. Natl. Acad. Sci. USA 96: 1263812643.
103. Ochman,, H., and, I. B. Jones. 2000. Evolutionary dynamics of full genome content in Escherichia coli. EMBO J. 19: 66376643.
104. Ochman,, H.,, J. G. Lawrence, and, E. A. Groisman. 2000. Lateral gene transfer and the nature of bacterial innovation. Nature 405: 299304.
105. Ochman,, H., and, N. A. Moran. 2001. Genes lost and genes found: evolution of bacterial pathogenesis and symbiosis. Science 292: 10961099.
106. Ochman,, H., and, A. C. Wilson. 1987. Evolution in bacteria: evidence for a universal substitution rate in cellular genomes. J. Mol. Evol. 26: 7486.
107. Ochman, H., and, A. C. Wilson. 1987. Evolutionary history of enteric bacteria, p. 1649–1654. In F. C. Neidhardt,, J. L. Ingraham,, K. B. Low,, B. Magasanik,, M. Shaechter, and, H. E. Umbarger (ed.), Escherichia coli and Salmonella typhimurium: Molecular and Cellular Aspects, vol. 2. American Society for Microbiology, Washington, D. C.
108. Oliver,, A.,, R. Canton,, P. Campo,, F. Baquero, and, J. Blazquez. 2000. High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288: 12511254.
109. Parish,, T.,, D. A. Smith,, G. Roberts,, J. Betts, and, N. G. Stoker. 2003. The senX3-regX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence. Microbiology 149: 14231435.
110. Pedulla,, M. L.,, M. E. Ford,, J. M. Houtz,, T. Karthikeyan,, C. Wadsworth,, J. A. Lewis,, D. Jacobs-Sera,, J. Falbo,, J. Gross,, N. R. Pannunzio,, W. Brucker,, V. Kumar,, J. Kandasamy,, L. Keenan,, S. Bardarov,, J. Kriakov,, J. G. Lawrence,, W. R. Jacobs, Jr.,, R. W. Hendrix, and, G. F. Hatfull. 2003. Origins of highly mosaic mycobacteriophage genomes. Cell 113: 171182.
111. Pelicic,, V.,, J. M. Reyrat, and, B. Gicquel. 1998. Genetic advances for studying Mycobacterium tuberculosis pathogenicity. Mol. Microbiol. 28: 413420.
112. Perez, E.,, S. Samper,, Y. Bordas,, C. Guilhot,, B. Gicquel, and, C. Martin. 2001. An essential role for phoP in Mycobacterium tuberculosis virulence. Mol. Microbiol. 41: 179187.
113. Pethe,, K.,, S. Alonso,, F. Biet,, G. Delogu,, M. J. Brennan,, C. Locht, and, F. D. Menozzi. 2001. The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination. Nature 412: 190194.
114. Pfyffer,, G. E.,, R. Auckenthaler, J. D. van Embden, and, D. van Soolingen. 1998. Mycobacterium canettii, the smooth variant of M. tuberculosis, isolated from a Swiss patient exposed in Africa. Emerg. Infect. Dis. 4: 631634.
115. Poulet,, S., and, S. T. Cole. 1995. Characterization of the highly abundant polymorphic GC-rich-repetitive sequence (PGRS) present in Mycobacterium tuberculosis. Arch. Microbiol. 163: 8795.
116. 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.
117. Pym,, A. S.,, P. Domenech,, N. Honore,, J. Song,, V. Deretic, and, S. T. Cole. 2001. Regulation of catalase-peroxidase (KatG) expression, isoniazid sensitivity and virulence by furA of Mycobacterium tuberculosis. Mol. Microbiol. 40: 879889.
118. Pym,, A. S.,, B. Saint-Joanis, and, S. T. Cole. 2002. Effect of katG mutations on the virulence of Mycobacterium tuberculosis and the implication for transmission in humans. Infect. Immun. 70: 49554960.
119. Ramakrishnan,, L.,, N. A. Federspiel, and, S. Falkow. 2000. Granuloma-specific expression of Mycobacterium virulence proteins from the glycine-rich PE-PGRS family. Science 288: 14361439.
120. Reed,, M. B.,, P. Domenech,, C. Manca,, H. Su,, A. K. Barczak,, B. N. Kreiswirth,, G. Kaplan, and, C. E. Barry III. 2004. A glycolipid of hypervirulent tuberculosis strains that inhibits the innate immune response. Nature 431: 8487.
121. Reyrat,, J. M., and, D. Kahn. 2001. Myco-bacterium smegmatis: an absurd model for tuberculosis? Trends Microbiol. 9: 472474.
122. Rogall,, T.,, J. Wolters,, T. Flohr, and, E. C. Bottger. 1990. Towards a phylogeny and definition of species at the molecular level within the genus Mycobacterium. Int. J. Syst. Bacteriol. 40: 323330.
123. Saint-Joanis,, B.,, H. Souchon,, M. Wilming,, K. Johnsson,, P. M. Alzari, and, S. T. Cole. 1999. Use of site-directed mutagenesis to probe the structure, function and isoniazid activation of the catalase/peroxidase, KatG, from Mycobacterium tuberculosis. Biochem. J. 338: 753760.
124. Salama,, N.,, K. Guillemin,, T. K. McDaniel,, G. Sherlock,, L. Tompkins, and, S. Falkow. 2000. A whole-genome microarray reveals genetic diversity among Helicobacter pylori strains. Proc. Natl. Acad. Sci. USA 97: 1466814673.
125. Salamon, H.,, M. Kato-Maeda,, P. M. Small,, J. Drenkow, and, T. R. Gingeras. 2000. Detection of deleted genomic DNA using a semiautomated computational analysis of GeneChip data. Genome Res. 10: 20442054.
126. Sharp,, P. M. 1991. Determinants of DNA sequence divergence between Escherichia coli and Salmonella typhimurium: codon usage, map position and concerted evolution. J. Mol. Evol. 33: 2333.
127. Shigenobu, S.,, H. Watanabe,, M. Hattori,, Y. Sakaki, and, H. Ishikawa. 2000. Genome sequence of the endocellular bacterial symbiont of aphids Buchnera sp. APS. Nature 407: 8186.
128. Sirakova,, T. D.,, V. S. Dubey,, M. H. Cynamon, and, P. E. Kolattukudy. 2003. Attenuation of Mycobacterium tuberculosis by disruption of a mas- like gene or a chalcone synthase-like gene, which causes deficiency in dimycocerosyl phthiocerol synthesis. J. Bacteriol. 185: 29993008.
129. Sirakova, T. D.,, V. S. Dubey,, H. J. Kim,, M. H. Cynamon, and, P. E. Kolattukudy. 2003. The largest open reading frame (pks12) in the Mycobacterium tuberculosis genome is involved in pathogenesis and dimycocerosyl phthiocerol synthesis. Infect. Immun. 71: 37943801.
130. Small,, P. M.,, P. C. Hopewell,, S. P. Singh,, A. Paz,, J. Parsonnet,, D. C. Ruston,, G. F. Schecter,, C. L. Daley, and, G. K. Schoolnik. 1994. The epidemiology of tuberculosis in San Francisco. A population-based study using conventional and molecular methods. N. Engl. J. Med. 330: 17031709.
131. Smith,, J. M.,, N. H. Smith, M. O’Rourke, and B. G. Spratt. 1993. How clonal are bacteria? Proc. Natl. Acad. Sci. USA 90: 43844388.
132. Sokurenko,, E. V.,, D. L. Hasty, and, D. E. Dykhuizen. 1999. Pathoadaptive mutations: gene loss and variation in bacterial pathogens. Trends Microbiol. 7: 191195.
133. Sola,, C.,, I. Filliol,, E. Legrand,, S. Lesjean,, C. Locht,, P. Supply, and, N. Rastogi. 2003. Genotyping of the Mycobacterium tuberculosis complex using MIRUs: association with VNTR and spoligotyping for molecular epidemiology and evolutionary genetics. Infect. Genet. Evol. 3: 125133.
134. 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 Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination. Proc. Natl. Acad. Sci. USA 94: 98699874.
135. Stahl,, D. A., and, J. W. Urbance. 1990. The division between fast- and slow-growing species corresponds to natural relationships among the mycobacteria. J. Bacteriol. 172: 116124.
136. Stephens,, R. S.,, S. Kalman,, C. Lammel,, J. Fan,, R. Marathe,, L. Aravind,, W. Mitchell,, L. Olinger,, R. L. Tatusov,, Q. Zhao,, E. V. Koonin, and, R. W. Davis. 1998. Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282: 754759.
137. Stinear,, T. P.,, A. Mve-Obiang,, P. L. 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. USA 101: 13451349.
138. Sturgill-Koszycki, S.,, P. H. Schlesinger,, P. Chakraborty,, P. L. Haddix,, H. L. Collins,, A. K. Fok,, R. D. Allen,, S. L. Gluck,, J. Heuser, and, D. G. Russell. 1994. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science 263: 678681.
139. Suerbaum,, S.,, J. M. Smith,, K. Bapumia,, G. Morelli,, N. H. Smith,, E. Kunstmann,, I. Dyrek, and, M. Achtman. 1998. Free recombination within Helicobacter pylori. Proc. Natl. Acad. Sci. USA 95: 1261912624.
140. 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.
141. Supply, P.,, R. M. Warren,, A. L. Banuls,, S. Lesjean,, G. D. Van Der Spuy,, L. A. Lewis,, M. Tibayrenc,, P. D. Van Helden, and, C. Locht. 2003. Linkage disequilibrium between minisatellite loci supports clonal evolution of Mycobacterium tuberculosis in a high tuberculosis incidence area. Mol. Microbiol. 47: 529538.
142. Thoen,, C. O.,, W. D. Richards, and, J. L. Jarnagin. 1977. Mycobacteria isolated from exotic animals. J. Am. Vet. Med. Assoc. 170: 987990.
143. Thorel, M. F.,, C. Karoui,, A. Varnerot,, C. Fleury, and, V. Vincent. 1998. Isolation of Mycobacterium bovis from baboons, leopards and a sea-lion. Vet. Res. 29: 207212.
144. Timpe,, R. D., and, E. H. Runyon. 1954. The relationship of “atypical” acid-fast bacteria to human disease. Lab. Clin. Med. 44: 202209.
145. Tizard,, M.,, T. Bull,, D. Millar,, T. Doran,, H. Martin,, N. Sumar,, J. Ford, and, J. Hermon-Taylor. 1998. A low G+C content genetic island in Mycobacterium avium subsp. paratuberculosis and M. avium subsp. silvaticum with homologous genes in Mycobacterium tuberculosis. Microbiology 144 (Pt.12): 34133423.
146. Tortoli, E. 2003. Impact of genotypic studies on mycobacterial taxonomy: the new mycobacteria of the 1990s. Clin. Microbiol. Rev. 16: 319354.
147. Tsolaki, A. G.,, A. E. Hirsh,, K. DeRiemer,, J. A. Enciso,, M. Z. Wong,, M. Hannan,, Y. O. Goguet de la Salmoniere,, K. Aman,, M. Kato-Maeda, and, P. M. Small. 2004. Functional and evolutionary genomics of Mycobacterium tuberculosis: insights from genomic deletions in 100 strains. Proc. Natl. Acad. Sci. USA 101: 48654870.
148. 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: 39273936.
149. Valway,, S. E.,, M. P. Sanchez,, T. F. Shinnick,, I. Orme,, T. Agerton,, D. Hoy,, J. S. Jones,, H. Westmoreland, and, I. M. Onorato. 1998. An outbreak involving extensive transmission of a virulent strain of Mycobacterium tuberculosis. N. Engl. J. Med. 338: 633639.
150. van Embden,, J. D.,, T. van Gorkom, K. Kremer,, R. Jansen,, B. A. van Der Zeijst, and, L. M. Schouls. 2000. Genetic variation and evolutionary origin of the direct repeat locus of Mycobacterium tuberculosis complex bacteria. J. Bacteriol. 182: 23932401.
151. van Helden,, P. D.,, R. M. Warren,, T. C. Victor,, G. van der Spuy,, M. Richardson, and, E. Hoal-van Helden. 2002. Strain families of Mycobacterium tuberculosis. Trends Microbiol. 10: 167168; author reply 168.
152. van Soolingen,, D.,, T. Hoogenboezem,, P. E. de Haas,, P. W. Hermans,, M. A. Koedam,, 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 of the Mycobacterium tuberculosis complex, Canetti: characterization of an exceptional isolate from Africa. Int. J. Syst. Bacteriol. 47: 12361245.
153. van Soolingen, D.,, L. Qian,, P. E. de Haas,, J. T. Douglas,, H. Traore,, F. Portaels,, H. Z. Qing,, D. Enkhsaikan,, P. Nymadawa, and, J. D. van Embden. 1995. Predominance of a single genotype of Mycobacterium tuberculosis in countries of east Asia. J. Clin. Microbiol. 33: 32343238.
154. Vera-Cabrera, L.,, M. A. Hernandez-Vera,, O. Welsh,, W. M. Johnson, and, J. Castro-Garza. 2001. Phospholipase region of Mycobacterium tuberculosis is a preferential locus for IS6110 transposition. J. Clin. Microbiol. 39: 34993504.
155. Vergne,, I.,, J. Chua, and, V. Deretic. 2003. Tuberculosis toxin blocking phagosome maturation inhibits a novel Ca2 +/calmodulin-PI3K hVPS34 cascade. J. Exp. Med. 198: 653659.
156. Viana-Niero, C.,, C. Gutierrez,, C. Sola,, I. Filliol,, F. Boulahbal,, V. Vincent, and, N. Rastogi. 2001. Genetic diversity of Mycobacterium africanum clinical isolates based on IS6110-restriction fragment length polymorphism analysis, spoligotyping, and variable number of tandem DNA repeats. J. Clin. Microbiol. 39: 5765.
157. Wagner,, P. L., and, M. K. Waldor. 2002. Bacteriophage control of bacterial virulence. Infect. Immun. 70: 39853993.
158. 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: 18001804.
159. 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. Tuber. Lung Dis. 80: 185189.
160. Wayne,, L. G. 1985. The “atypical” mycobacteria; recognition and disease association. Crit. Rev. Microbiol. 26: 185222.
161. 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 immunodeficient mice. Mol. Microbiol. 35: 10171025.
162. Werngren,, J., and, S. E. Hoffner. 2003. Drug-susceptible Mycobacterium tuberculosis Beijing genotype does not develop mutation-conferred resistance to rifampin at an elevated rate. J. Clin. Microbiol. 41: 15201524.
163. Wilson,, T. M.,, G. de Lisle, and, D. M. Collins. 1995. Effect of inhA and katG on isoniazid resistance and virulence of Mycobacterium bovis. Mol. Microbiol. 15: 10091015.
164. Woolfit,, M., and, L. Bromham. 2003. Increased rates of sequence evolution in endosymbiotic bacteria and fungi with small effective population sizes. Mol. Biol. Evol. 20: 15451555.
165. Xu,, S.,, A. Cooper,, S. Sturgill-Koszycki,, T. van Heyningen,, D. Chatterjee,, I. Orme,, P. Allen, and, D. G. Russell. 1994. Intracellular trafficking in Mycobacterium tuberculosis and Mycobacterium avium-infected macrophages. J. Immunol. 153: 25682578.
166. Yeh,, R. W.,, P. C. Hopewell, and, C. L. Daley. 1999. Simultaneous infection with two strains of Mycobacterium tuberculosis identified by restriction fragment length polymorphism analysis. Int. J. Tuberc. Lung Dis. 3: 537539.
167. Zahrt,, T. C., and, V. Deretic. 2001. Mycobacterium tuberculosis signal transduction system required for persistent infections. Proc. Natl. Acad. Sci. USA 98: 1270612711.
168. Zhang,, Y.,, B. Heym,, B. Allen,, D. Young, and, S. Cole. 1992. The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature 358: 591593.


Generic image for table

Sizes of complete or nearly complete mycobacterial genome sequences

Citation: Pym A, Small P. 2006. Mycobacterial Evolution: Insights from Genomics and Population Genetics, p 301-325. In Seifert H, DiRita V (ed), Evolution of Microbial Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815622.ch16
Generic image for table

Selected experimentally defined virulence factors of

Citation: Pym A, Small P. 2006. Mycobacterial Evolution: Insights from Genomics and Population Genetics, p 301-325. In Seifert H, DiRita V (ed), Evolution of Microbial Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815622.ch16

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