Multiple thioredoxin-mediated routes to detoxify hydroperoxides in Mycobacterium tuberculosis.

作者: Timo Jaeger , Heike Budde , Leopold Flohé , Ulrich Menge , Mahavir Singh

DOI: 10.1016/J.ABB.2003.11.021

关键词: Mycobacterium tuberculosisPeroxynitriteBiochemistryIsoniazidBiologyMycothiolAntioxidantThioredoxin reductaseThioredoxinMicrobiologyPeroxiredoxin

摘要: Drug resistance and virulence of Mycobacterium tuberculosis are in part related to the pathogen’s antioxidant defense systems. KatG− strains resistant first line tuberculostatic isoniazid but need compensate their catalase deficiency by alternative peroxidase systems stay virulent. So far, only NADH-driven AhpD-mediated hydroperoxide reduction AhpC has been implicated as such virulence-determining mechanism. We here report on two novel pathways which underscore importance thioredoxin system for M. tuberculosis: (i) NADPH-driven that is mediated reductase C (ii) atypical peroxiredoxin TPx equally depends can use both, B C. Kinetic analyses with different hydroperoxides including peroxynitrite qualify redox cascade comprising reductase, C, most efficient protect against oxidative nitrosative stress situ.

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