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

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.