The effects of reactive nitrogen intermediates on gene expression in Mycobacterium tuberculosis |
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Authors: | Ohno Hideaki Zhu Guofeng Mohan Vellore P Chu Darien Kohno Shigeru Jacobs William R Chan John |
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Institution: | Departments of Medicine and; Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.; Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, 852-8501, Japan.; Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA. |
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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. |
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