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Journal of Bacteriology, August 2004, p. 5427-5431, Vol. 186, No. 16
0021-9193/04/$08.00+0 DOI: 10.1128/JB.186.16.5427-5431.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
and Vojo Deretic2*
College of Pharmacy, Toxicology Program,1 Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131,2 Department of Biochemistry and Molecular Biology and Section of Hematology Research, Mayo Clinic and Foundation, Rochester, Minnesota 559053
Received 16 February 2004/ Accepted 11 May 2004
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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