1887

Abstract

Members of the complex show distinct host preferences, yet the molecular basis for this tropism is unknown. Comparison of the and genome sequences revealed no unique genes in the bovine pathogen per se, indicating that differences in gene expression may play a significant role in host predilection. To define the key gene expression differences between and we have performed transcriptome analyses of cultures grown under steady-state conditions in a chemostat. This revealed that the human and bovine pathogens show differential expression of genes encoding a range of functions, including cell wall and secreted proteins, transcriptional regulators, PE/PPE proteins, lipid metabolism and toxin–antitoxin pairs. Furthermore, we probed the gene expression response of and to an acid-shock perturbation which triggered a notably different expression response in the two strains. Through these approaches we have defined a core gene set that shows differential expression between the human and bovine tubercle bacilli, and the biological implications are discussed.

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2007-10-01
2024-03-29
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References

  1. Alam M. S., Garg S. K., Agrawal P. 2007; Molecular function of WhiB4/Rv3681c of Mycobacterium tuberculosis H37Rv: a [4Fe–4S] cluster co-ordinating protein disulphide reductase. Mol Microbiol 63:1414–1431
    [Google Scholar]
  2. Arcus V. L., Rainey P. B., Turner S. J. 2005; The PIN-domain toxin-antitoxin array in mycobacteria. Trends Microbiol 13:360–365
    [Google Scholar]
  3. Bacon J., James B. W., Wernisch L., Williams A., Morley K. A., Hatch G. J., Mangan J. A., Hinds J., Stoker N. G. other authors 2004; The influence of reduced oxygen availability on pathogenicity and gene expression in Mycobacterium tuberculosis . Tuberculosis (Edinb 84:205–217
    [Google Scholar]
  4. Balaji B., O'Connor K., Lucas J. R., Anderson J. M., Csonka L. N. 2005; Timing of induction of osmotically controlled genes in Salmonella enterica serovar Typhimurium , determined with quantitative real-time reverse transcription-PCR. Appl Environ Microbiol 71:8273–8283
    [Google Scholar]
  5. Bhatt K., Gurcha S. S., Bhatt A., Besra G. S., Jacobs W. R. Jr 2007; Two polyketide-synthase-associated acyltransferases are required for sulfolipid biosynthesis in Mycobacterium tuberculosis . Microbiology 153:513–520
    [Google Scholar]
  6. Booth I. R. 1985; Regulation of cytoplasmic pH in bacteria. Microbiol Rev 49:359–378
    [Google Scholar]
  7. Boshoff H. I., Myers T. G., Copp B. R., McNeil M. R., Wilson M. A., Barry C. E. III 2004; The transcriptional responses of Mycobacterium tuberculosis to inhibitors of metabolism: novel insights into drug mechanisms of action. J Biol Chem 279:40174–40184
    [Google Scholar]
  8. Camacho L. R., Constant P., Raynaud C., Laneelle M. A., Triccas J. A., Gicquel B., Daffe M., Guilhot C. 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 276:19845–19854
    [Google Scholar]
  9. Chan J., Silver R. F., Kampmann B., Wallis R. S. 2005; Intracellular models of Mycobacterium tuberculosis infection. . In Tuberculosis and the Tubercle Bacillus pp 437–461 Edited by Cole S. T., Eisenach K. D., McMurray D. N, Jacobs W. R. Jr Washington, DC: American Society for Microbiology;
    [Google Scholar]
  10. Charlet D., Mostowy S., Alexander D., Sit L., Wiker H. G., Behr M. A. 2005; Reduced expression of antigenic proteins MPB70 and MPB83 in Mycobacterium bovis BCG strains due to a start codon mutation in sigK . Mol Microbiol 56:1302–1313
    [Google Scholar]
  11. Cole S. T., Brosch R., Parkhill J., Garnier T., Churcher C., Harris D., Gordon S. V., Eiglmeier K., Gas S. other authors 1998; Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537–544
    [Google Scholar]
  12. Cole S. T., Eiglmeier K., Parkhill J., James K. D., Thomson N. R., Wheeler P. R., Honoré N., Garnier T., Churcher C. other authors 2001; Massive gene decay in the leprosy bacillus. Nature 409:1007–1011
    [Google Scholar]
  13. Constant P., Perez E., Malaga W., Laneelle M. A., Saurel O., Daffe M., Guilhot C. 2002; Role of the pks15 / 1 gene in the biosynthesis of phenolglycolipids in the M. tuberculosis complex: evidence that all strains synthesize glycosylated P-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbour a frameshift mutation in the pks15 / 1 gene. J Biol Chem 277:38148–38158
    [Google Scholar]
  14. Converse S. E., Mougous J. D., Leavell M. D., Leary J. A., Bertozzi C. R., Cox J. S. 2003; MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence. Proc Natl Acad Sci U S A 100:6121–6126
    [Google Scholar]
  15. Correia F. F., D'Onofrio A., Rejtar T., Li L., Karger B. L., Makarova K., Koonin E. V., Lewis K. 2006; Kinase activity of overexpressed HipA is required for growth arrest and multidrug tolerance in Escherichia coli . J Bacteriol 188:8360–8367
    [Google Scholar]
  16. Davis N. K., Chater K. F. 1992; The Streptomyces coelicolor whiB gene encodes a small transcription factor-like protein dispensable for growth but essential for sporulation. Mol Gen Genet 232:351–358
    [Google Scholar]
  17. Downing K. J., Betts J. C., Young D. I., McAdam R. A., Kelly F., Young M., Mizrahi V. 2004; Global expression profiling of strains harbouring null mutations reveals that the five rpf -like genes of Mycobacterium tuberculosis show functional redundancy. Tuberculosis (Edinb 84:167–179
    [Google Scholar]
  18. Dubey V. S., Sirakova T. D., Kolattukudy P. E. 2002; Disruption of msl3 abolishes the synthesis of mycolipanoic and mycolipenic acids required for polyacyltrehalose synthesis in Mycobacterium tuberculosis H37Rv and causes cell aggregation. Mol Microbiol 45:1451–1459
    [Google Scholar]
  19. Dubos R. J., Davis B. D. 1946; Factors affecting the growth of tubercle bacilli in liquid media. J Exp Med 83:409–423
    [Google Scholar]
  20. Fisher M. A., Plikaytis B. B., Shinnick T. M. 2002; Microarray analysis of the Mycobacterium tuberculosis transcriptional response to the acidic conditions found in phagosomes. J Bacteriol 184:4025–4032
    [Google Scholar]
  21. Garnier T., Eiglmeier K., Camus J. C., Medina N., Mansoor H., Pryor M., Duthoy S., Grondin S., Lacroix C. other authors 2003; The complete genome sequence of Mycobacterium bovis . Proc Natl Acad Sci U S A 100:7877–7882
    [Google Scholar]
  22. Geiman D. E., Raghunand T. R., Agarwal N., Bishai W. R. 2006; Differential gene expression in response to exposure to antimycobacterial agents and other stress conditions among seven Mycobacterium tuberculosis whiB -like genes. Antimicrob Agents Chemother 50:2836–2841
    [Google Scholar]
  23. Gerdes K., Christensen S. K., Lobner-Olesen A. 2005; Prokaryotic toxin-antitoxin stress response loci. Nat Rev Microbiol 3:371–382
    [Google Scholar]
  24. Goldstone D., Baker E. N., Metcalf P. 2005; Crystallization and preliminary diffraction studies of the C-terminal domain of the DipZ homologue from Mycobacterium tuberculosis . Acta Crystallograph Sect F Struct Biol Cryst Commun 61:243–245
    [Google Scholar]
  25. Gonzalo Asensio J., Maia C., Ferrer N. L., Barilone N., Laval F., Soto C. Y., Winter N., Daffé M., Gicquel B. other authors 2006; The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis . J Biol Chem 281:1313–1316
    [Google Scholar]
  26. Grogan D. W., Cronan J. E Jr. 1997; Cyclopropane ring formation in membrane lipids of bacteria. Microbiol Mol Biol Rev 61:429–441
    [Google Scholar]
  27. Hewinson R. G., Michell S. L., Russell W. P., McAdam R. A., Jacobs W. R. Jr 1996; Molecular characterization of MPT83: a seroreactive antigen of Mycobacterium tuberculosis with homology to MPT70. Scand J Immunol 43:490–499
    [Google Scholar]
  28. Hoskisson P. A., Hobbs G. 2005; Continuous culture – making a comeback?. Microbiology 151:3153–3159
    [Google Scholar]
  29. Ishii N., Nakahigashi K., Baba T., Robert M., Soga T., Kanai A., Hirasawa T., Naba M., Hirai K. other authors 2007; Multiple high-throughput analyses monitor the response of E. coli to perturbations. Science 316:593–597
    [Google Scholar]
  30. Jain S. K., Paul-Satyaseela M., Lamichhane G., Kim K. S., Bishai W. R. 2006; Mycobacterium tuberculosis invasion and traversal across an in vitro human blood-brain barrier as a pathogenic mechanism for central nervous system tuberculosis. J Infect Dis 193:1287–1295
    [Google Scholar]
  31. Jakimowicz P., Cheesman M. R., Bishai W. R., Chater K. F., Thomson A. J., Buttner M. J. 2005; Evidence that the Streptomyces developmental protein WhiD, a member of the WhiB family, binds a [4Fe–4S] cluster. J Biol Chem 280:8309–8315
    [Google Scholar]
  32. James B. W., Williams A., Marsh P. D. 2000; The physiology and pathogenicity of Mycobacterium tuberculosis grown under controlled conditions in a defined medium. J Appl Microbiol 88:669–677
    [Google Scholar]
  33. Jungblut P. R., Schaible U. E., Mollenkopf H. J., Zimny-Arndt U., Raupach B., Mattow J., Halada P., Lamer S., Hagens K., Kaufmann S. H. other authors 1999; Comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis BCG strains: towards functional genomics of microbial pathogens. Mol Microbiol 33:1103–1117
    [Google Scholar]
  34. Kadokura H., Katzen F., Beckwith J. 2003; Protein disulfide bond formation in prokaryotes. Annu Rev Biochem 72:111–135
    [Google Scholar]
  35. Keating L. A., Wheeler P. R., Mansoor H., Inwald J. K., Dale J., Hewinson R. G., Gordon S. V. 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 56:163–174
    [Google Scholar]
  36. Keren I., Shah D., Spoering A., Kaldalu N., Lewis K. 2004; Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli . J Bacteriol 186:8172–8180
    [Google Scholar]
  37. Malli R., Epstein W. 1998; Expression of the Kdp ATPase is consistent with regulation by turgor pressure. J Bacteriol 180:5102–5108
    [Google Scholar]
  38. Maurer L. M., Yohannes E., Bondurant S. S., Radmacher M., Slonczewski J. L. 2005; pH regulates genes for flagellar motility, catabolism, and oxidative stress in Escherichia coli K-12. J Bacteriol 187:304–319
    [Google Scholar]
  39. Mostowy S., Cleto C., Sherman D. R., Behr M. A. 2004; The Mycobacterium tuberculosis complex transcriptome of attenuation. Tuberculosis (Edinb 84:197–204
    [Google Scholar]
  40. Mostowy S., Inwald J., Gordon S., Martin C., Warren R., Kremer K., Cousins D., Behr M. A. 2005; Revisiting the evolution of Mycobacterium bovis . J Bacteriol 187:6386–6395
    [Google Scholar]
  41. Pandey D. P., Gerdes K. 2005; Toxin–antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes. Nucleic Acids Res 33:966–976
    [Google Scholar]
  42. Rehren G., Walters S., Fontan P., Smith I., Zarraga A. M. 2007; Differential gene expression between Mycobacterium bovis and Mycobacterium tuberculosis . Tuberculosis (Edinb 87:347–359
    [Google Scholar]
  43. Rodrigue S., Brodeur J., Jacques P. E., Gervais A. L., Brzezinski R., Gaudreau L. 2007; Identification of mycobacterial sigma factor binding sites by chromatin immunoprecipitation assays. J Bacteriol 189:1505–1513
    [Google Scholar]
  44. Rosas-Magallanes V., Stadthagen-Gomez G., Rauzier J., Barreiro L. B., Tailleux L., Boudou F., Griffin R., Nigou J., Jackson M. other authors; 2007; Signature-tagged transposon mutagenesis identifies novel Mycobacterium tuberculosis genes involved in the parasitism of human macrophages. Infect Immun 75:504–507
    [Google Scholar]
  45. Said-Salim B., Mostowy S., Kristof A. S., Behr M. A. 2006; Mutations in Mycobacterium tuberculosis Rv0444c, the gene encoding anti-SigK, explain high level expression of MPB70 and MPB83 in Mycobacterium bovis . Mol Microbiol 62:1251–1263
    [Google Scholar]
  46. Sassetti C. M., Rubin E. J. 2003; Genetic requirements for mycobacterial survival during infection. Proc Natl Acad Sci U S A 100:12989–12994
    [Google Scholar]
  47. Schnappinger D., Ehrt S., Voskuil M. I., Liu Y., Mangan J. A., Monahan I. M., Dolganov G., Efron B., Butcher P. A. other authors 2003; Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: insights into the phagosomal environment. J Exp Med 198:693–704
    [Google Scholar]
  48. Singh A., Jain S., Gupta S., Das T., Tyagi A. K. 2003; mymA operon of Mycobacterium tuberculosis : its regulation and importance in the cell envelope. FEMS Microbiol Lett 227:53–63
    [Google Scholar]
  49. Sirakova T. D., Thirumala A. K., Dubey V. S., Sprecher H., Kolattukudy P. E. 2001; The Mycobacterium tuberculosis pks2 gene encodes the synthase for the hepta- and octamethyl-branched fatty acids required for sulfolipid synthesis. J Biol Chem 276:16833–16839
    [Google Scholar]
  50. Smith N. H., Kremer K., Inwald J., Dale J., Driscoll J. R., Gordon S. V., van Soolingen D., Hewinson R. G., Smith J. M. 2006; Ecotypes of the Mycobacterium tuberculosis complex. J Theor Biol 239:220–225
    [Google Scholar]
  51. Stermann M., Sedlacek L., Maass S., Bange F. C. 2004; A promoter mutation causes differential nitrate reductase activity of Mycobacterium tuberculosis and Mycobacterium bovis . J Bacteriol 186:2856–2861
    [Google Scholar]
  52. Stewart G. R., Wernisch L., Stabler R., Mangan J. A., Hinds J., Laing K. G., Young D. B., Butcher P. D. 2002; Dissection of the heat-shock response in Mycobacterium tuberculosis using mutants and microarrays. Microbiology 148:3129–3138
    [Google Scholar]
  53. Sulzenbacher G., Canaan S., Bordat Y., Neyrolles O., Stadthagen G., Roig-Zamboni V., Rauzier J., Maurin D., Laval F. other authors 2006; LppX is a lipoprotein required for the translocation of phthiocerol dimycocerosates to the surface of Mycobacterium tuberculosis . EMBO J 25:1436–1444
    [Google Scholar]
  54. van Soolingen D., de Haas P. E., Haagsma J., Eger T., Hermans P. W., Ritacco V., Alito A., van Embden J. D. 1994; Use of various genetic markers in differentiation of Mycobacterium bovis strains from animals and humans and for studying epidemiology of bovine tuberculosis. J Clin Microbiol 32:2425–2433
    [Google Scholar]
  55. Walters S. B., Dubnau E., Kolesnikova I., Laval F., Daffe M., Smith I. 2006; The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol Microbiol 60:312–330
    [Google Scholar]
  56. Weeks D. L., Eskandari S., Scott D. R., Sachs G. 2000; A H+-gated urea channel: the link between Helicobacter pylori urease and gastric colonization. Science 287:482–485
    [Google Scholar]
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