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Raman, Sahadevan; Song, Taeksun; Puyang, Xiaoling; Bardarov, Stoyan; Jacobs, William R.; Husson, Robert N.

The Alternative Sigma Factor SigH Regulates Major Components of Oxidative and Heat Stress Responses inMycobacterium tuberculosis

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  • Medientyp: E-Artikel
  • Titel: The Alternative Sigma Factor SigH Regulates Major Components of Oxidative and Heat Stress Responses inMycobacterium tuberculosis
  • Beteiligte: Raman, Sahadevan; Song, Taeksun; Puyang, Xiaoling; Bardarov, Stoyan; Jacobs, William R.; Husson, Robert N.
  • Erschienen: American Society for Microbiology, 2001
  • Erschienen in: Journal of Bacteriology
  • Sprache: Englisch
  • DOI: 10.1128/jb.183.20.6119-6125.2001
  • ISSN: 0021-9193; 1098-5530
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>ABSTRACT</jats:title><jats:p><jats:italic>Mycobacterium tuberculosis</jats:italic>is 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 saprophyte<jats:italic>Mycobacterium smegmatis</jats:italic>. In this work we investigated the role of<jats:italic>sigH</jats:italic>in the<jats:italic>M</jats:italic>.<jats:italic>tuberculosis</jats:italic>response to heat and oxidative stress. We determined that a<jats:italic>M</jats:italic>.<jats:italic>tuberculosis sigH</jats:italic>mutant is more susceptible to oxidative stresses and that the inducible expression of the thioredoxin reductase/thioredoxin genes<jats:italic>trxB2/trxC</jats:italic>and a gene of unknown function, Rv2466c, is regulated by<jats:italic>sigH</jats:italic>via expression from promoters directly recognized by SigH. We also determined that the<jats:italic>sigH</jats:italic>mutant is more susceptible to heat stress and that inducible expression of the heat shock genes<jats:italic>dnaK</jats:italic>and<jats:italic>clpB</jats:italic>is positively regulated by<jats:italic>sigH</jats:italic>. 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 of<jats:italic>sigH</jats:italic>in the<jats:italic>M</jats:italic>.<jats:italic>tuberculosis</jats:italic>stress response, we investigated the regulation of the stress-responsive sigma factor genes<jats:italic>sigE</jats:italic>and<jats:italic>sigB</jats:italic>. We determined that inducible expression of<jats:italic>sigE</jats:italic>is regulated by<jats:italic>sigH</jats:italic>and that basal and inducible expression of<jats:italic>sigB</jats:italic>is dependent on<jats:italic>sigE</jats:italic>and<jats:italic>sigH</jats:italic>. These data indicate that<jats:italic>sigH</jats:italic>plays a central role in a network that regulates heat and oxidative-stress responses that are likely to be important in<jats:italic>M</jats:italic>.<jats:italic>tuberculosis</jats:italic>pathogenesis.</jats:p>
  • Zugangsstatus: Freier Zugang