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J Bacteriol. 2004 Aug;186(16):5427-31.

Requirements for nitric oxide generation from isoniazid activation in vitro and inhibition of mycobacterial respiration in vivo.

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1
College of Pharmacy, Toxicology Program, University of New Mexico Health Sciences Center, Albuquerque, 87131, USA.

Abstract

Isoniazid (INH), a front-line antituberculosis agent, is activated by mycobacterial catalase-peroxidase KatG, converting INH into bactericidal reactive species. Here we investigated the requirements and the pathway of nitric oxide (NO*) generation during oxidative activation of INH by Mycobacterium tuberculosis KatG in vitro. We also provide in vivo evidence that INH-derived NO* can inhibit key mycobacterial respiratory enzymes, which may contribute to the overall antimycobacterial action of INH.

PMID:
15292144
PMCID:
PMC490879
DOI:
10.1128/JB.186.16.5427-5431.2004
[Indexed for MEDLINE]
Free PMC Article
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