The effects of reactive nitrogen intermediates on gene expression in Mycobacterium tuberculosis

Hideaki Ohno, Guofeng Zhu, Vellore P. Mohan, Darien Chu, Shigeru Kohno, William R. Jacobs, John Chan

Research output: Contribution to journalReview article

147 Scopus citations

Abstract

Nitric oxide (NO) and related reactive nitrogen intermediates (RNI) are effective antimycobacterial agents and signal-transducing molecules. The present study uses microarray analysis to examine the effects of RNI on Mycobacterium tuberculosis gene expression. A common set of 53 genes was regulated by two chemically distinct nitric oxide donors. For a subset of the RNI-inducible genes, evidence exists suggesting that they may play a role in promoting survival of the tubercle bacillus in the host. Results obtained from studies based on a murine experimental tuberculosis model involving nos2-deficient mice suggest that RNI could regulate M. tuberculosis gene expression in vivo. Finally, there is a remarkable overlap between the RNI-inducible regulon and that previously reported to be regulated by hypoxia; and both reactive nitrogen species and anaerobicity upregulate the expression of one and the same putative two-component regulatory response system. Together, the results of this study provide evidence suggesting that (i) RNI play a role in regulating M. tuberculosis gene expression in vivo; (ii) the reactive nitrogen species upregulate genes that may be conducive to the survival of the tubercle bacillus in the infected host; and (iii) RNI and hypoxia may regulate mycobacterial gene expression via overlapping signal transduction pathways.

Original languageEnglish (US)
Pages (from-to)637-648
Number of pages12
JournalCellular Microbiology
Volume5
Issue number9
DOIs
StatePublished - Sep 1 2003

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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