Pyruvate:ferredoxin oxidoreductase and thioredoxin reductase are involved in 5-nitroimidazole activation while flavin metabolism is linked to 5-nitroimidazole resistance in Giardia lamblia | Zendy

David Leitsch | Zendy; Anita G. Burgess | Zendy; Linda A. Dunn | Zendy; Kenia G. Krauer | Zendy; Kevin S. W. Tan | Zendy; Michael Duchêne | Zendy; Peter Upcroft | Zendy; Lars Eckmann | Zendy; J. A. Upcroft | Zendy

Open Access

Pyruvate:ferredoxin oxidoreductase and thioredoxin reductase are involved in 5-nitroimidazole activation while flavin metabolism is linked to 5-nitroimidazole resistance in Giardia lamblia

Author(s) -

David Leitsch,

Anita G. Burgess,

Linda A. Dunn,

Kenia G. Krauer,

Kevin S. W. Tan,

Michael Duchêne,

Peter Upcroft,

Lars Eckmann,

J. A. Upcroft

Publication year - 2011

Publication title -

journal of antimicrobial chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.124

H-Index - 194

eISSN - 1460-2091

pISSN - 0305-7453

DOI - 10.1093/jac/dkr192

Subject(s) - nitroimidazole , oxidoreductase , ferredoxin , giardia lamblia , biochemistry , reductase , chemistry , flavodoxin , biology , microbiology and biotechnology , flavin group , enzyme , organic chemistry

The mechanism of action of, and resistance to, metronidazole in the anaerobic (or micro-aerotolerant) protozoan parasite Giardia lamblia has long been associated with the reduction of ferredoxin (Fd) by the enzyme pyruvate:ferredoxin oxidoreductase (PFOR) and the subsequent activation of metronidazole by Fd to toxic radical species. Resistance to metronidazole has been associated with down-regulation of PFOR and Fd. The aim of this study was to determine whether the PFOR/Fd couple is the only pathway involved in metronidazole activation in Giardia.

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