Requirements for nitric oxide generation from isoniazid activation in vitro and inhibition of mycobacterial respiration in vivo |
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Authors: | Timmins Graham S Master Sharon Rusnak Frank Deretic Vojo |
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Institution: | College of Pharmacy, Toxicology Program, University of New Mexico Health Sciences Center, Albuquerque, 87131, USA. |
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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. |
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