The Alternative Sigma Factor SigH Regulates Major Components of Oxidative and Heat Stress Responses inMycobacterium tuberculosis
10.1128/jb.183.20.6119-6125.2001
Crossref journal-article
American Society for Microbiology
Journal of Bacteriology (235)
Abstract

ABSTRACTMycobacterium tuberculosisis a specialized intracellular pathogen that must regulate gene expression to overcome stresses produced by host defenses during infection. SigH is an alternative sigma factor that we have previously shown plays a role in the response to stress of the saprophyteMycobacterium smegmatis. In this work we investigated the role ofsigHin theM.tuberculosisresponse to heat and oxidative stress. We determined that aM.tuberculosis sigHmutant is more susceptible to oxidative stresses and that the inducible expression of the thioredoxin reductase/thioredoxin genestrxB2/trxCand a gene of unknown function, Rv2466c, is regulated bysigHvia expression from promoters directly recognized by SigH. We also determined that thesigHmutant is more susceptible to heat stress and that inducible expression of the heat shock genesdnaKandclpBis positively regulated bysigH. The induction of these heat shock gene promoters but not of other SigH-dependent promoters was markedly greater in response to heat versus oxidative stress, consistent with their additional regulation by a heat-labile repressor. To further understand the role ofsigHin theM.tuberculosisstress response, we investigated the regulation of the stress-responsive sigma factor genessigEandsigB. We determined that inducible expression ofsigEis regulated bysigHand that basal and inducible expression ofsigBis dependent onsigEandsigH. These data indicate thatsigHplays a central role in a network that regulates heat and oxidative-stress responses that are likely to be important inM.tuberculosispathogenesis.

Bibliography

Raman, S., Song, T., Puyang, X., Bardarov, S., Jacobs, W. R., & Husson, R. N. (2001). The Alternative Sigma Factor SigH Regulates Major Components of Oxidative and Heat Stress Responses inMycobacterium tuberculosis. Journal of Bacteriology, 183(20), 6119–6125.

Authors 6
  1. Sahadevan Raman (first)
  2. Taeksun Song (additional)
  3. Xiaoling Puyang (additional)
  4. Stoyan Bardarov (additional)
  5. William R. Jacobs (additional)
  6. Robert N. Husson (additional)
References 57 Referenced 241
  1. Adams L. B. Dinauer M. C. Morgenstern D. E. Krahenbuhl J. L. Comparison of the roles of reactive oxygen and nitrogen intermediates in the host response to Mycobacterium tuberculosis using transgenic mice.Tuber. Lung Dis.781997237246 (10.1016/S0962-8479(97)90004-6) / Tuber. Lung Dis. / Comparison of the roles of reactive oxygen and nitrogen intermediates in the host response to Mycobacterium tuberculosis using transgenic mice by Adams L. B. (1997)
  2. 10.1128/iai.55.9.2223-2229.1987
  3. 10.1128/jb.179.19.5999-6004.1997
  4. 10.1084/jem.175.4.1111
  5. 10.1128/IAI.68.10.5575-5580.2000
  6. Christman M. F. Morgan R. W. Jacobson F. S. Ames B. N. Positive control of a regulon for defenses against oxidative stress and some heat-shock proteins in Salmonella typhimurium.Cell411985753762 (10.1016/S0092-8674(85)80056-8) / Cell / Positive control of a regulon for defenses against oxidative stress and some heat-shock proteins in Salmonella typhimurium by Christman M. F. (1985)
  7. 10.1038/31159
  8. Cox J. S. Chen B. McNeil M. Jacobs W. R. Jr. Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice.Nature40219997983 (10.1038/47042) / Nature / Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice by Cox J. S. (1999)
  9. DeMaio J. Zhang Y. Ko C. Young D. Bishai W. A stationary-phase stress-response sigma factor from Mycobacterium tuberculosis.Proc. Natl. Acad. Sci. USA93199627902794 (10.1073/pnas.93.7.2790) / Proc. Natl. Acad. Sci. USA / A stationary-phase stress-response sigma factor from Mycobacterium tuberculosis by DeMaio J. (1996)
  10. Deretic V. Philipp W. Dhandayuthapani S. Mudd M. H. Curcic R. Garbe T. Heym B. Via L. E. Cole S. T. Mycobacterium tuberculosis is a natural mutant with an inactivated oxidative-stress regulatory gene: implications for sensitivity to isoniazid.Mol. Microbiol.171995889900 (10.1111/j.1365-2958.1995.mmi_17050889.x) / Mol. Microbiol. / Mycobacterium tuberculosis is a natural mutant with an inactivated oxidative-stress regulatory gene: implications for sensitivity to isoniazid by Deretic V. (1995)
  11. 10.1001/jama.282.7.677
  12. 10.1128/JB.181.14.4266-4274.1999
  13. Fratazzi C. Arbeit R. D. Carini C. Remold H. G. Programmed cell death of Mycobacterium avium serovar 4-infected human macrophages prevents the mycobacteria from spreading and induces mycobacterial growth inhibition by freshly added, uninfected macrophages.J. Immunol.158199743204327 (10.4049/jimmunol.158.9.4320) / J. Immunol. / Programmed cell death of Mycobacterium avium serovar 4-infected human macrophages prevents the mycobacteria from spreading and induces mycobacterial growth inhibition by freshly added, uninfected macrophages by Fratazzi C. (1997)
  14. Glickman M. S. Cox J. S. Jacobs W. R. Jr. A novel mycolic acid cyclopropane synthetase is required for coding, persistence, and virulence of Mycobacterium tuberculosis.Mol. Cell52000717727 (10.1016/S1097-2765(00)80250-6) / Mol. Cell / A novel mycolic acid cyclopropane synthetase is required for coding, persistence, and virulence of Mycobacterium tuberculosis by Glickman M. S. (2000)
  15. Goloubinoff P. Mogk A. Zvi A. P. Tomoyasu T. Bukau B. Sequential mechanism of solubilization and refolding of stable protein aggregates by a bichaperone network.Proc. Natl. Acad. Sci. USA9619991373213737 (10.1073/pnas.96.24.13732) / Proc. Natl. Acad. Sci. USA / Sequential mechanism of solubilization and refolding of stable protein aggregates by a bichaperone network by Goloubinoff P. (1999)
  16. Graham J. E. Clark-Curtiss J. E. Identification of Mycobacterium tuberculosis RNAs synthesized in response to phagocytosis by human macrophages by selective capture of transcribed sequences (SCOTS).Proc. Natl. Acad. Sci. USA9619991155411559 (10.1073/pnas.96.20.11554) / Proc. Natl. Acad. Sci. USA / Identification of Mycobacterium tuberculosis RNAs synthesized in response to phagocytosis by human macrophages by selective capture of transcribed sequences (SCOTS) by Graham J. E. (1999)
  17. Grandvalet C. de Crecy-Lagard V. Mazodier P. The ClpB ATPase of Streptomyces albus G belongs to the HspR heat shock regulon.Mol. Microbiol.311999521532 (10.1046/j.1365-2958.1999.01193.x) / Mol. Microbiol. / The ClpB ATPase of Streptomyces albus G belongs to the HspR heat shock regulon by Grandvalet C. (1999)
  18. Grossman A. Erickson J. Gross C. The htpR gene product of E. coli is a sigma factor for heat-shock promoters.Cell381984383390 (10.1016/0092-8674(84)90493-8) / Cell / The htpR gene product of E. coli is a sigma factor for heat-shock promoters by Grossman A. (1984)
  19. 10.1016/0003-9861(79)90289-3
  20. 10.1128/JB.181.2.469-476.1999
  21. 10.1128/JB.180.15.3765-3770.1998
  22. Husson R. Young R. Genes for the major protein antigens of Mycobacterium tuberculosis: the etiologic agents of tuberculosis and leprosy share an immunodominant antigen.Proc. Natl. Acad. Sci. USA84198716791683 (10.1073/pnas.84.6.1679) / Proc. Natl. Acad. Sci. USA / Genes for the major protein antigens of Mycobacterium tuberculosis: the etiologic agents of tuberculosis and leprosy share an immunodominant antigen by Husson R. (1987)
  23. Kang J. G. Paget M. S. Seok Y. J. Hahn M. Y. Bae J. B. Hahn J. S. Kleanthous C. Buttner M. J. Roe J. H. RsrA, an anti-sigma factor regulated by redox change.EMBO J.18199942924298 (10.1093/emboj/18.15.4292) / EMBO J. / RsrA, an anti-sigma factor regulated by redox change by Kang J. G. (1999)
  24. Kosower N. Kosower E. Diamide: an oxidant probe for thiols.Methods Enzymol.2511995123133 (10.1016/0076-6879(95)51116-4) / Methods Enzymol. / Diamide: an oxidant probe for thiols by Kosower N. (1995)
  25. Lee B. Y. Horwitz M. A. Identification of macrophage and stress-induced proteins of Mycobacterium tuberculosis.J. Clin. Investig.961995245249 (10.1172/JCI118028) / J. Clin. Investig. / Identification of macrophage and stress-induced proteins of Mycobacterium tuberculosis by Lee B. Y. (1995)
  26. Lee M. H. Pascopella L. Jacobs W. R. Jr. Hatfull G. F. Site-specific integration of mycobacteriophage L5: integration-proficient vectors for Mycobacterium smegmatis, Mycobacterium tuberculosis, and bacille Calmette-Guerin.Proc. Natl. Acad. Sci. USA88199131113115 (10.1073/pnas.88.8.3111) / Proc. Natl. Acad. Sci. USA / Site-specific integration of mycobacteriophage L5: integration-proficient vectors for Mycobacterium smegmatis, Mycobacterium tuberculosis, and bacille Calmette-Guerin by Lee M. H. (1991)
  27. Manabe Y. C. Saviola B. J. Sun L. Murphy J. R. Bishai W. R. Attenuation of virulence in Mycobacterium tuberculosis expressing a constitutively active iron repressor.Proc. Natl. Acad. Sci. USA9619991284412848 (10.1073/pnas.96.22.12844) / Proc. Natl. Acad. Sci. USA / Attenuation of virulence in Mycobacterium tuberculosis expressing a constitutively active iron repressor by Manabe Y. C. (1999)
  28. Manca C. Paul S. Barry C. E. III Freedman V. H. Kaplan G. Mycobacterium tuberculosis catalase and peroxidase activities and resistance to oxidative killing in human monocytes in vitro.Infect. Immun.6719997479 (10.1128/IAI.67.1.74-79.1999) / Infect. Immun. / Mycobacterium tuberculosis catalase and peroxidase activities and resistance to oxidative killing in human monocytes in vitro by Manca C. (1999)
  29. 10.1046/j.1365-2958.1999.01212.x
  30. 10.1038/35021074
  31. Middlebrook G. Cohn M. Some observations on the pathogenicity of isoniazid-resistant variants of tubercle bacilli.Science1181953297299 (10.1126/science.118.3063.297) / Science / Some observations on the pathogenicity of isoniazid-resistant variants of tubercle bacilli by Middlebrook G. (1953)
  32. Mitchison D. Selkon J. Lloyd J. Virulence in the guinea pig, susceptibility to hydrogen peroxide, and catalase activity of isoniazid-sensitive tubercle bacilli from South Indian and British patients.J. Pathol. Bacteriol.861963464468 (10.1002/path.1700860213) / J. Pathol. Bacteriol. / Virulence in the guinea pig, susceptibility to hydrogen peroxide, and catalase activity of isoniazid-sensitive tubercle bacilli from South Indian and British patients by Mitchison D. (1963)
  33. 10.1128/JB.181.9.2846-2851.1999
  34. Mogk A. Tomoyasu T. Goloubinoff P. Rudiger S. Roder D. Langen H. Bukau B. Identification of thermolabile Escherichia coli proteins: prevention and reversion of aggregation by DnaK and ClpB.EMBO J.18199969346949 (10.1093/emboj/18.24.6934) / EMBO J. / Identification of thermolabile Escherichia coli proteins: prevention and reversion of aggregation by DnaK and ClpB by Mogk A. (1999)
  35. Motohashi K. Watanabe Y. Yohda M. Yoshida M. Heat-inactivated proteins are rescued by the DnaK·J-GrpE set and ClpB chaperones.Proc. Natl. Acad. Sci. USA96199971847189 (10.1073/pnas.96.13.7184) / Proc. Natl. Acad. Sci. USA / Heat-inactivated proteins are rescued by the DnaK·J-GrpE set and ClpB chaperones by Motohashi K. (1999)
  36. Narberhaus F. Negative regulation of bacterial heat shock genes.Mol. Microbiol.31199918 (10.1046/j.1365-2958.1999.01166.x) / Mol. Microbiol. / Negative regulation of bacterial heat shock genes by Narberhaus F. (1999)
  37. 10.1128/JB.180.18.4856-4864.1998
  38. Paget M. S. Bae J. B. Hahn M. Y. Li W. Kleanthous C. Roe J. H. Buttner M. J. Mutational analysis of RsrA, a zinc-binding anti-sigma factor with a thiol-disulphide redox switch.Mol. Microbiol.39200110361047 (10.1046/j.1365-2958.2001.02298.x) / Mol. Microbiol. / Mutational analysis of RsrA, a zinc-binding anti-sigma factor with a thiol-disulphide redox switch by Paget M. S. (2001)
  39. Paget M. S. Kang J. G. Roe J. H. Buttner M. J. sigmaR, an RNA polymerase sigma factor that modulates expression of the thioredoxin system in response to oxidative stress in Streptomyces coelicolor A3(2).EMBO J.17199857765782 (10.1093/emboj/17.19.5776) / EMBO J. / sigmaR, an RNA polymerase sigma factor that modulates expression of the thioredoxin system in response to oxidative stress in Streptomyces coelicolor A3(2) by Paget M. S. (1998)
  40. Pelicic V. Jackson M. Reyrat J.-M. Jacobs W. J. Gicquel B. Guilhot C. Efficient allelic exchange and transposon mutagenesis in Mycobacterium tuberculosis.Proc. Natl. Acad. Sci. USA9419971095510960 (10.1073/pnas.94.20.10955) / Proc. Natl. Acad. Sci. USA / Efficient allelic exchange and transposon mutagenesis in Mycobacterium tuberculosis by Pelicic V. (1997)
  41. Pym A. S. Domenech P. Honoré N. Song J. Deretic V. Cole S. T. Regulation of catalase-peroxidase (KatG) expression, isoniazid sensitivity and virulence by furA of Mycobacterium tuberculosis.Mol. Microbiol.402001879889 (10.1046/j.1365-2958.2001.02427.x) / Mol. Microbiol. / Regulation of catalase-peroxidase (KatG) expression, isoniazid sensitivity and virulence by furA of Mycobacterium tuberculosis by Pym A. S. (2001)
  42. Raina S. Missiakas D. Georgopoulos C. The rpoE gene encoding the ςE (ς24) heat shock sigma factor of Escherichia coli.EMBO J.14199510431055 (10.1002/j.1460-2075.1995.tb07085.x) / EMBO J. / The rpoE gene encoding the ςE (ς24) heat shock sigma factor of Escherichia coli by Raina S. (1995)
  43. Rouviere P. De Las Penas A. Lu C. Rudd K. Gross C. rpoE, the gene encoding the second heat-shock sigma factor, ςE, in Escherichia coli.EMBO J.14199510321042 (10.1002/j.1460-2075.1995.tb07084.x) / EMBO J. / rpoE, the gene encoding the second heat-shock sigma factor, ςE, in Escherichia coli by Rouviere P. (1995)
  44. Segal R. Ron E. Z. Regulation and organization of the groE and dnaK operons in Eubacteria.FEMS Microbiol. Lett.1381996110 (10.1111/j.1574-6968.1996.tb08126.x) / FEMS Microbiol. Lett. / Regulation and organization of the groE and dnaK operons in Eubacteria by Segal R. (1996)
  45. Sherman D. R. Sabo P. J. Hickey M. J. Arain T. M. Mahairas G. G. Yuan Y. Barry C. E. III Stover C. K. Disparate responses to oxidative stress in saprophytic and pathogenic mycobacteria.Proc. Natl. Acad. Sci. USA92199566256629 (10.1073/pnas.92.14.6625) / Proc. Natl. Acad. Sci. USA / Disparate responses to oxidative stress in saprophytic and pathogenic mycobacteria by Sherman D. R. (1995)
  46. Silva C. L. Lowrie D. B. Identification and characterization of murine cytotoxic T cells that kill Mycobacterium tuberculosis.Infect. Immun.68200032693274 (10.1128/IAI.68.6.3269-3274.2000) / Infect. Immun. / Identification and characterization of murine cytotoxic T cells that kill Mycobacterium tuberculosis by Silva C. L. (2000)
  47. Snapper S. B. Melton R. E. Mustafa S. Kieser T. Jacobs W. R. Jr. Isolation and characterization of efficient plasmid transformation mutants of Mycobacterium smegmatis.Mol. Microbiol.4199019111919 (10.1111/j.1365-2958.1990.tb02040.x) / Mol. Microbiol. / Isolation and characterization of efficient plasmid transformation mutants of Mycobacterium smegmatis by Snapper S. B. (1990)
  48. 10.1128/AAC.41.3.600
  49. Stewart G. R. Snewin V. A. Walzl G. Hussell T. Tormay P. O'Gaora P. Goyal M. Betts J. Brown I. N. Young D. B. Overexpression of heat-shock proteins reduces survival of Mycobacterium tuberculosis in the chronic phase of infection.Nat. Med.72001732737 (10.1038/89113) / Nat. Med. / Overexpression of heat-shock proteins reduces survival of Mycobacterium tuberculosis in the chronic phase of infection by Stewart G. R. (2001)
  50. 10.1016/0022-2836(89)90104-6
  51. Ting L. M. Kim A. C. Cattamanchi A. Ernst J. D. Mycobacterium tuberculosis inhibits IFN-gamma transcriptional responses without inhibiting activation of STAT1.J. Immunol.163199938983906 (10.4049/jimmunol.163.7.3898) / J. Immunol. / Mycobacterium tuberculosis inhibits IFN-gamma transcriptional responses without inhibiting activation of STAT1 by Ting L. M. (1999)
  52. Wilson T. M. de Lisle G. W. Collins D. M. Effect of inhA and katG on isoniazid resistance and virulence of Mycobacterium bovis.Mol. Microbiol.15199510091015 (10.1111/j.1365-2958.1995.tb02276.x) / Mol. Microbiol. / Effect of inhA and katG on isoniazid resistance and virulence of Mycobacterium bovis by Wilson T. M. (1995)
  53. 10.1128/jb.179.9.2922-2929.1997
  54. Zahrt T. C. Song J. Siple J. Deretic V. Mycobacterial FurA is a negative regulator of catalase-peroxidase gene katG.Mol. Microbiol.39200111741185 (10.1111/j.1365-2958.2001.02321.x) / Mol. Microbiol. / Mycobacterial FurA is a negative regulator of catalase-peroxidase gene katG by Zahrt T. C. (2001)
  55. Zhang Y. Dhandayuthapani S. Deretic V. Molecular basis for the exquisite sensitivity of Mycobacterium tuberculosis to isoniazid.Proc. Natl. Acad. Sci. USA9319961321213216 (10.1073/pnas.93.23.13212) / Proc. Natl. Acad. Sci. USA / Molecular basis for the exquisite sensitivity of Mycobacterium tuberculosis to isoniazid by Zhang Y. (1996)
  56. 10.1038/358591a0
  57. 10.1128/jb.176.5.1359-1363.1994
Dates
Type When
Created 23 years, 1 month ago (July 27, 2002, 5:58 a.m.)
Deposited 2 years, 4 months ago (April 23, 2023, 10:58 a.m.)
Indexed 1 month, 1 week ago (July 20, 2025, 12:18 a.m.)
Issued 23 years, 10 months ago (Oct. 15, 2001)
Published 23 years, 10 months ago (Oct. 15, 2001)
Published Print 23 years, 10 months ago (Oct. 15, 2001)
Funders 0

None

@article{Raman_2001, title={The Alternative Sigma Factor SigH Regulates Major Components of Oxidative and Heat Stress Responses inMycobacterium tuberculosis}, volume={183}, ISSN={1098-5530}, url={http://dx.doi.org/10.1128/jb.183.20.6119-6125.2001}, DOI={10.1128/jb.183.20.6119-6125.2001}, number={20}, journal={Journal of Bacteriology}, publisher={American Society for Microbiology}, author={Raman, Sahadevan and Song, Taeksun and Puyang, Xiaoling and Bardarov, Stoyan and Jacobs, William R. and Husson, Robert N.}, year={2001}, month=oct, pages={6119–6125} }