1887

Abstract

Two-component systems are important constituents of bacterial regulatory networks. Results of this investigation into the role of the MprAB two-component system of indicate that it is associated with the regulation of several stress-responsive regulons. Using a deletion mutant lacking portions of the response regulator, MprA, and the histidine kinase, MprB, it was demonstrated by real-time PCR, primer extension analyses and DNA microarrays that MprAB activates sigma factor genes and , under SDS stress and during exponential growth. SDS-inducible, MprA-dependent transcriptional start points were identified for , and , and variations in distance between these points and MprA-binding sites suggest that MprA is involved in different mechanisms of promoter activation. Although most of the SigE regulon was downregulated in the deletion mutant, the cluster of genes Rv1129c, Rv1130 and Rv1131, which is associated with growth in monoctyes, was upregulated in the deletion mutant under SDS stress, and this upregulation was dependent upon atmospheric growth conditions. Multiple stress-associated genes of the DosR, SigD and IdeR regulons were also upregulated in the deletion mutant, during exponential growth and/or in the presence of SDS. Surprisingly, the deletion mutant had increased resistance to SDS compared to the parental strain, and enhanced growth in human peripheral blood monocytes, characteristics which may result from a loss of repression of stress-associated genes.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.29281-0
2007-04-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/micro/153/4/1229.html?itemId=/content/journal/micro/10.1099/mic.0.29281-0&mimeType=html&fmt=ahah

References

  1. Ando M., Yoshimatsu T., Ko C., Converse P. J., Bishai W. R. 2003; Deletion of Mycobacterium tuberculosis sigma factor E results in delayed time to death with bacterial persistence in the lungs of aerosol-infected mice. Infect Immun 71:7170–7172 [CrossRef]
    [Google Scholar]
  2. Betts J. C., Lukey P. T., Robb L. C., McAdam R. A., Duncan K. 2002; Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol Microbiol 43:717–731 [CrossRef]
    [Google Scholar]
  3. Boon C., Dick T. 2002; Mycobacterium bovis BCG response regulator essential for hypoxic dormancy. J Bacteriol 184:6760–6767 [CrossRef]
    [Google Scholar]
  4. Busby S., Ebright R. H. 1999; Transcription activation by catabolite activator protein (CAP. J Mol Biol 293:199–213 [CrossRef]
    [Google Scholar]
  5. Byrd T. F. 1997; Tumor necrosis factor α (TNF α ) promotes growth of virulent Mycobacterium tuberculosis in human monocytes. Iron-mediated growth suppression is correlated with decreased release of TNF- α from iron-treated, infected monocytes. J Clin Invest 99:2518–2529 [CrossRef]
    [Google Scholar]
  6. Byrd T. F., Horwitz M. 1989; Interferon gamma-activated human monocytes downregulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. J Clin Invest 83:1457–1465 [CrossRef]
    [Google Scholar]
  7. Calamita H., Ko C., Tyagi S., Yoshimatsu T., Morrison N. E., Bishai W. R. 2005; The Mycobacterium tuberculosis SigD sigma factor controls the expression of ribosome-associated gene products in stationary phase and is required for full virulence. Cell Microbiol 7:233–244
    [Google Scholar]
  8. Cohen-Gonsaud M., Barthe P., Bagneris C., Henderson B., Ward J., Roumestand C., Keep N. H. 2005; The structure of a resuscitation-promoting factor domain from Mycobacterium tuberculosis shows homology to lysozymes. Nat Struct Mol Biol 12:270–273 [CrossRef]
    [Google Scholar]
  9. Cole S. T., Brosch R., Parkhill J., Garnier T., Churcher C., Harris D., Gordon S. V., Eiglemeier K., Gas S. other authors 1998; Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537–544 [CrossRef]
    [Google Scholar]
  10. Corbett L., Raviglione M. C. 2005; Global burden of tuberculosis: past, present and future. In Tuberculosis and the Tubercle Bacilli pp 3–12 Edited by Cole S. T. Eisenach K. D., McMurray D. N., Jacobs W. R. Jr Washington, DC: American Society for Microbiology;
    [Google Scholar]
  11. De Voss J. J., Rutter K., Schroeder B. G., Barry C. E. , 3rd. 1999; Iron acquisition and metabolism by mycobacteria. J Bacteriol 181:4443–4451
    [Google Scholar]
  12. De Voss J. J., Rutter K., Schroeder B. G., Su H., Zhu Y., Barry C. E. , 3rd. (2000; The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages. Proc Natl Acad Sci U S A 97:1252–1257 [CrossRef]
    [Google Scholar]
  13. Downing K. J., Mischenko V. V., Shleeva M. O., Young D. I., Young M., Kaprelyants A. S., Apt A. S., Mizrahi V. 2005; Mutants of Mycobacterium tuberculosis lacking three of the five rpf -like genes are defective for growth in vivo and for resuscitation in vitro. Infect Immun 73:3038–3043 [CrossRef]
    [Google Scholar]
  14. 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 [CrossRef]
    [Google Scholar]
  15. Dudoit S., Yang Y. H., Callow M. J., Speed T. P. 2000; Statistical methods for identifying differentially expressed genes in replicated cDNA microarray experiments. Technical Report no. 578 Stanford University;
  16. Dussurget O., Timm J., Gomez M., Gold B., Yu S., Sabol S. Z., Holmes R. K., Jacobs W. R. Jr, Smith I. 1999; Transcriptional control of the iron-responsive fxbA gene by the mycobacterial regulator IdeR. J Bacteriol 181:3402–3408
    [Google Scholar]
  17. Geiman D. E., Kaushal D., Ko C., Tyagi S., Manabe Y. C., Schroeder B. G., Fleischmann R. D., Morrsion N. E., Converse P. J. other authors 2004; Attenuation of late-stage disease in mice infected by the Mycobacterium tuberculosis mutant lacking the SigF alternate sigma factor and identification of SigF-dependent genes by microarray analysis. Infect Immun 72:1733–1745 [CrossRef]
    [Google Scholar]
  18. Gold B., Rodriguez G. M., Marras S. A., Pentecost M., Smith I. 2001; The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages. Mol Microbiol 42:851–865
    [Google Scholar]
  19. He H., Zahrt T. C. 2005; Identification and characterization of a regulatory sequence recognized by Mycobacterium tuberculosis persistence regulator MprA. J Bacteriol 187:202–212 [CrossRef]
    [Google Scholar]
  20. He H., Hovey R., Kane J., Singh V., Zahrt T. C. 2006; MprAB is a stress-responsive two-component system that directly regulates expression of sigma factors SigB and SigE in Mycobacterium tuberculosis . J Bacteriol 188:2134–2143 [CrossRef]
    [Google Scholar]
  21. Hoch J. A., Varughese K. I. 2001; Keeping signals straight in phosphorelay signal transduction. J Bacteriol 183:4941–4949 [CrossRef]
    [Google Scholar]
  22. Jacques P. E., Gervais A. L., Cantin M., Lucier J. F., Dallaire G., Drouin G., Gaudreau L., Goulet J., Brzezinski R. 2005; MtbRegList, a database dedicated to the analysis of transcriptional regulation in Mycobacterium tuberculosis . Bioinformatics 21:2563–2565 [CrossRef]
    [Google Scholar]
  23. 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 [CrossRef]
    [Google Scholar]
  24. Jensen-Cain D. M., Quinn F. D. 2001; Differential expression of sigE by Mycobacterium tuberculosis during intracellular growth. Microb Pathog 30:271–278 [CrossRef]
    [Google Scholar]
  25. Karakousis P. C., Yoshimatsu T., Lamichhane G., Woolwine S. C., Nuermberger E. L., Grosset J., Bishai W. R. 2004; Dormancy phenotype displayed by extracellular Mycobacterium tuberculosis within artificial granulomas in mice. J Exp Med 200:647–657 [CrossRef]
    [Google Scholar]
  26. Kendall S. L., Movahedzadeh F., Rison S. C., Wernisch L., Parish T., Duncan K., Betts J. C., Stoker N. G. 2004; The Mycobacterium tuberculosis dosRS two-component system is induced by multiple stresses. Tuberculosis 84:247–255 [CrossRef]
    [Google Scholar]
  27. Manabe Y. C., Saviola B. J., Sun L., Murphy J. R., Bishai W. R. 1999; Attenuation of virulence in Mycobacterium tuberculosis expressing a constitutively active iron repressor. Proc Natl Acad Sci U S A 96:12844–12848 [CrossRef]
    [Google Scholar]
  28. Manabe Y. C., Hatem C. L., Kesavan A. K., Durack J., Murphy J. R. 2005; Both Corynebacterium diphtheriae DtxR(E175K) and Mycobacterium tuberculosis IdeR(D177K) are dominant positive repressors of IdeR-regulated genes in M. tuberculosis . Infect Immun 73:5988–5994 [CrossRef]
    [Google Scholar]
  29. Manganelli R., Dubnau E., Tyagi S., Kramer F. R., Smith I. 1999; Differential expression of 10 sigma factor genes in Mycobacterium tuberculosis . Mol Microbiol 31:715–724 [CrossRef]
    [Google Scholar]
  30. Manganelli R., Voskuil M. I., Schoolnik G. K., Smith I. 2001; The Mycobacterium tuberculosis ECF sigma factor σ E: role in global gene expression and survival in macrophages. Mol Microbiol 41:423–437 [CrossRef]
    [Google Scholar]
  31. Manganelli R., Voskuil M. I., Schoolnik G. K., Dubnau E., Gomez M., Smith I. 2002; Role of the extracytoplasmic-function σ factor σ H in Mycobacterium tuberculosis global gene expression. Mol Microbiol 45:365–374 [CrossRef]
    [Google Scholar]
  32. Manganelli R., Fattorini L., Tan D., Iona E., Orefici G., Altavilla G., Cusatelli P., Smith I. 2004; The extra cytoplasmic function sigma factor σ E is essential for Mycobacterium tuberculosis virulence in mice. Infect Immun 72:3038–3041 [CrossRef]
    [Google Scholar]
  33. Mattow J., Siejak F., Hagens K., Becher D., Albrecht D., Krah A., Schmidt F., Jungblut P. R., Kaufmann S. H., Schaible U. E. 2006; Proteins unique to intraphagosomally grown Mycobacterium tuberculosis . Proteomics 6:2485–2494 [CrossRef]
    [Google Scholar]
  34. Mecsas J., Rouviere P. E., Erickson J. W., Donohue T. J., Gross C. A. 1993; The activity of sigma E, an Escherichia coli heat-inducible sigma-factor, is modulated by expression of outer membrane proteins. Genes Dev 7:2618–2628 [CrossRef]
    [Google Scholar]
  35. Mukamolova G. V., Turapov O. A., Young D. I., Kaprelyants A. S., Kell D. B., Young M. 2002; A family of autocrine growth factors in Mycobacterium tuberculosis . Mol Microbiol 46:623–635 [CrossRef]
    [Google Scholar]
  36. Mukamolova G. V., Murzin A. G., Salina E. G., Demina G. R., Kell D. B., Kaprelyants A. S., Young M. 2006; Muralytic activity of Micrococcus luteus Rpf and its relationship to physiological activity in promoting bacterial growth and resuscitation. Mol Microbiol 59:84–98 [CrossRef]
    [Google Scholar]
  37. Nachin L., Nannmark U., Nystrom T. 2005; Differential roles of the universal stress proteins of Escherichia coli in oxidative stress resistance, adhesion, and motility. J Bacteriol 187:6265–6272 [CrossRef]
    [Google Scholar]
  38. Ohno H., Zhu G., Mohan V. P., Chu D., Kohno S., Jacobs W. R. Jr, Chan J. 2003; The effects of reactive nitrogen intermediates on gene expression in Mycobacterium tuberculosis . Cell Microbiol 5:637–648 [CrossRef]
    [Google Scholar]
  39. O'Toole R., Williams H. D. 2003; Universal stress proteins and Mycobacterium tuberculosis . Res Microbiol 154:387–392 [CrossRef]
    [Google Scholar]
  40. O'Toole R., Smeulders M. J., Blokpoel M. C., Kay E. J., Lougheed K., Williams H. D. 2003; A two-component regulator of universal stress protein expression and adaptation to oxygen starvation in Mycobacterium smegmatis . J Bacteriol 185:1543–1554 [CrossRef]
    [Google Scholar]
  41. Parish T., Stoker N. G. 2000; Use of a flexible cassette method to generate a double unmarked Mycobacterium tuberculosis tlyA plcABC mutant by gene replacement. Microbiology 146:1969–1975
    [Google Scholar]
  42. Parish T., Smith D. A., Kendall S., Casali N., Bancroft G. J., Stoker N. G. 2003; Deletion of two-component regulatory systems increases the virulence of Mycobacterium tuberculosis . Infect Immun 71:1134–1140 [CrossRef]
    [Google Scholar]
  43. Park H. D., Guinn K. M., Harrell M. I., Liao R., Voskuil M. I., Tompa M., Schoolnik G. K., Sherman D. R. 2003; Rv3133c/ dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis . Mol Microbiol 48:833–843 [CrossRef]
    [Google Scholar]
  44. Perez E., Samper S., Bordas Y., Guilhot C., Gicquel B., Martin C. 2001; An essential role for phoP in Mycobacterium tuberculosis virulence. Mol Microbiol 41:179–187 [CrossRef]
    [Google Scholar]
  45. Prakash P., Pathak N., Hasnain S. E. 2005; pheA (Rv3838c) of Mycobacterium tuberculosis encodes an allosterically regulated monofunctional prephenate dehydratase that requires both catalytic and regulatory domains for optimum activity. J Biol Chem 280:20666–20671 [CrossRef]
    [Google Scholar]
  46. Raman S., Song T., Puyang X., Bardarov S., Jacobs W. R. Jr, Husson R. N. 2001; The alternative sigma factor SigH regulates major components of oxidative and heat stress responses in Mycobacterium tuberculosis . J Bacteriol 183:6119–6125 [CrossRef]
    [Google Scholar]
  47. Raman S., Hazra R., Dascher C. C., Husson R. N. 2004; Transcription regulation by the Mycobacterium tuberculosis alternative sigma factor SigD and its role in virulence. J Bacteriol 186:6605–6616 [CrossRef]
    [Google Scholar]
  48. Rison S. C. G., Kendall S. L., Movahedzadeh F., Stoker N. G. 2005; The mycobacterial two-component regulatory systems. In Mycobacterium Molecular Microbiology pp 29–69 Edited by Parish T. Wydmondham, Norfolk. UK: Horizon Biosciences;
    [Google Scholar]
  49. Saeed A. I., Sharov V., White J., Li J., Liang W., Bhagabati N., Braisted J., Klapa M. Currier T. other authors 2003; TM4: a free, open-source system for microarray data management and analysis. Biotechniques 34:374–378
    [Google Scholar]
  50. Samten B., Ghosh P., Yi A. K., Weis S. E., Lakey D. L., Gonsly R., Pendurthi U., Wizel B., Zhang Y. other authors 2002; Reduced expression of nuclear cyclic adenosine 5′-monophosphate response element-binding proteins and IFN-gamma promoter function in disease due to an intracellular pathogen. J Immunol 168:3520–3526 [CrossRef]
    [Google Scholar]
  51. Sassetti C. M., Boyd D. H., Rubin E. J. 2003; Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol 48:77–84 [CrossRef]
    [Google Scholar]
  52. Schnappinger D., Ehrt S., Voskuil M. I., Liu Y., Mangan J. A., Monahan I. M., Dolganov G., Efron B., Butcher P. D. other authors 2003; Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: insights into the phagosomal environment. J Exp Med 198:693–704 [CrossRef]
    [Google Scholar]
  53. Shalel-Levanon S., San K. Y., Bennett G. N. 2005; Effect of oxygen, and ArcA and FNR regulators on the expression of genes related to the electron transfer chain and the TCA cycle in Escherichia coli . Metab Eng 7:364–374 [CrossRef]
    [Google Scholar]
  54. Sharma K., Gupta M., Pathak M., Gupta N., Koul A., Sarangi S., Baweja R., Singh Y. 2006; Transcriptional control of the mycobacterial embCAB operon by PknH through a regulatory protein. EmbR, in vivo. J Bacteriol 188:2936–2944 [CrossRef]
    [Google Scholar]
  55. Sherman D. R., Voskuil M., Schnappinger D., Liao R., Harrell M. I., Schoolnik G. K. 2001; Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding α -crystallin. Proc Natl Acad Sci U S A 98:7534–7539 [CrossRef]
    [Google Scholar]
  56. Shi L., Sohaskey C. D., Kana B. D., Dawes S., North R. J., Mizrahi V., Gennaro M. L. 2005; Changes in energy metabolism of Mycobacterium tuberculosis in mouse lung and under in vitro conditions affecting aerobic respiration. Proc Natl Acad Sci U S A 102:15629–15634 [CrossRef]
    [Google Scholar]
  57. Sohaskey C. D., Wayne L. 2003; Role of narK2X and narGHJI in hypoxic upregulation of nitrate reduction by Mycobacterium tuberculosis . J Bacteriol 185:7247–7256 [CrossRef]
    [Google Scholar]
  58. Stover C. K., de la Cruz V. F., Fuerst T. R., Burlein J. E., Benson L. A., Bennett L. T., Bansal G. P., Young J. F., Lee M. H. other authors 1991; New use of BCG for recombinant vaccines. Nature 351:456–460 [CrossRef]
    [Google Scholar]
  59. Talaat A. M., Lyons R., Howard S. T., Johnston S. A. 2004; The temporal expression profile of Mycobacterium tuberculosis infection in mice. Proc Natl Acad Sci U S A 101:4602–4607 [CrossRef]
    [Google Scholar]
  60. Tam C., Missiakas D. 2005; Changes in lipopolysaccharide structure induce the σ E-dependent response of Escherichia coli . Mol Microbiol 55:1403–1412 [CrossRef]
    [Google Scholar]
  61. Tufariello J. M., Mi K., Xu J., Manabe Y. C., Kesavan A. K., Drumm J., Tanaka K., Jacobs W. R. Jr, Chan J. 2006; Deletion of the Mycobacterium tuberculosis resuscitation-promoting factor Rv1009 gene results in delayed reactivation from chronic tuberculosis. Infect Immun 74:2985–2995 [CrossRef]
    [Google Scholar]
  62. Tusher V. G., Tibshirani R., Chu G. 2001; Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A 98:5116–5121 [CrossRef]
    [Google Scholar]
  63. Voskuil M. I., Schnappinger D., Visconti K. C., Harrell M. I., Dolganov G. M., Sherman D. R., Schoolnik G. K. 2003; Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J Exp Med 198:705–713 [CrossRef]
    [Google Scholar]
  64. 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 [CrossRef]
    [Google Scholar]
  65. Wu Q. L., Kong D., Lam K., Husson R. N. 1997; A mycobacterial extracytoplasmic function sigma factor involved in survival following stress. J Bacteriol 179:2922–2929
    [Google Scholar]
  66. Wu S., Howard S. T., Lakey D. L., Kipnis A., Samten B., Safi H., Gruppo V., Wizel B., Shams H. other authors 2004; The principal sigma factor sigA mediates enhanced growth of Mycobacterium tuberculosis strains in vivo. Mol Microbiol 51:1551–1562 [CrossRef]
    [Google Scholar]
  67. Zahrt T. C., Deretic V. 2001; Mycobacterium tuberculosis signal transduction system required for persistent infections. Proc Natl Acad Sci U S A 98:12706–12711 [CrossRef]
    [Google Scholar]
  68. Zahrt T. C., Wozniak C., Jones D., Trevett A. 2003; Functional analysis of the Mycobacterium tuberculosis MprAB two-component signal transduction system. Infect Immun 71:6962–6970 [CrossRef]
    [Google Scholar]
  69. Zink A. R., Grabner W., Nerlich A. G. 2005; Molecular identification of human tuberculosis in recent and historic bone tissue samples: the role of molecular techniques for the study of historic tuberculosis. Am J Phys Anthropol 126:32–47 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.29281-0
Loading
/content/journal/micro/10.1099/mic.0.29281-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error