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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.

Requirements for Nitric Oxide Generation from Isoniazid Activation In Vitro and Inhibition of Mycobacterial Respiration In Vivo

Graham S. Timmins,1 Sharon Master,2 Frank Rusnak,3,{dagger} 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.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131. Phone: (505) 272-0291. Fax: (505) 272-5309. E-mail: vderetic{at}salud.unm.edu.

{dagger} Deceased.

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.



This article has been cited by other articles:

  • Pagan-Ramos, E., Master, S. S., Pritchett, C. L., Reimschuessel, R., Trucksis, M., Timmins, G. S., Deretic, V. (2006). Molecular and Physiological Effects of Mycobacterial oxyR Inactivation.. J. Bacteriol. 188: 2674-2680 [Abstract] [Full Text]  


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