Mechanism of Action of 5-Nitrothiophenes against Mycobacterium tuberculosis | Zendy

Ruben C. Hartkoorn | Zendy; O. B. Ryabova | Zendy; Laurent R. Chiarelli | Zendy; Giovanna Riccardi | Zendy; Vadim Makarov | Zendy; Stewart T. Cole | Zendy

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Mechanism of Action of 5-Nitrothiophenes against Mycobacterium tuberculosis

Author(s) -

Ruben C. Hartkoorn,

O. B. Ryabova,

Laurent R. Chiarelli,

Giovanna Riccardi,

Vadim Makarov,

Stewart T. Cole

Publication year - 2014

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.02693-13

Subject(s) - nitroreductase , mycobacterium tuberculosis , mechanism of action , streptomycin , mycobacterium , nitroimidazole , microbiology and biotechnology , chemistry , mutant , cofactor , tuberculosis , biology , bacteria , biochemistry , in vitro , antibiotics , enzyme , medicine , genetics , organic chemistry , pathology , gene

On using the streptomycin-starved 18b strain as a model for nonreplicatingMycobacterium tuberculosis , we identified a 5-nitrothiophene compound as highly active but not cytotoxic. Mutants resistant to 5-nitrothiophenes were found be cross-resistant to the nitroimidazole PA-824 and unable to produce the F420 cofactor. Furthermore, 5-nitrothiophenes were shown to be activated by the F420 -dependent nitroreductase Ddn and to release nitric oxide, a mechanism of action identical to that described for nitroimidazoles.

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