期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 423, 期 1, 页码 182-191出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2003.11.021
关键词
tuberculosis; thioredoxins; peroxiredoxins; mycothiol; alkyl hydroperoxide reduction; peroxynitrite; virulence; INH resistance
Drug resistance and virulence of Mycobacterium tuberculosis are in part related to the pathogen's antioxidant defense systems. KatG(-) strains are resistant to the first line tuberculostatic isoniazid but need to compensate their catalase deficiency by alternative peroxidase systems to stay virulent. So far, only NADH-driven and AhpD-mediated hydroperoxide reduction by AhpC has been implicated as such virulence-determining mechanism. We here report on two novel pathways which underscore the importance of the thioredoxin system for antioxidant defense in M. tuberculosis: (i) NADPH-driven hydroperoxide reduction by AhpC that is mediated by thioredoxin reductase and thioredoxin C and (ii) hydroperoxide reduction by the atypical peroxiredoxin TPx that equally depends on thioredoxin reductase but can use both, thioredoxin B and C. Kinetic analyses with different hydroperoxides including peroxynitrite qualify the redox cascade comprising thioredoxin reductase, thioredoxin Q and TPx as the most efficient system to protect M. tuberculosis against oxidative and nitrosative stress in situ. (C) 2003 Elsevier Inc. All rights reserved.
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