The effects of reactive nitrogen intermediates on gene expression in Mycobacterium tuberculosis.
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.
Ohno
Hideaki
H
Departments of Medicine and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Zhu
Guofeng
G
Mohan
Vellore P
VP
Chu
Darien
D
Kohno
Shigeru
S
Jacobs
William R
WR
Chan
John
J
D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D000860:Hypoxia; D008168:Lung / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000378:metabolism / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D020411:Oligonucleotide Array Sequence Analysis; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D018085:Regulon; D015203:Reproducibility of Results; D014376:Tuberculosis / Q000382:microbiology*
D020030:Nitric Oxide Donors; D026361:Reactive Nitrogen Species; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse