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Mechanism of action of 5-nitrothiophenes against Mycobacterium tuberculosis.

ABSTRACT: On using the streptomycin-starved 18b strain as a model for nonreplicating Mycobacterium 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.

SUBMITTER: Hartkoorn RC

PROVIDER: S-EPMC3993272 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Mechanism of action of 5-nitrothiophenes against Mycobacterium tuberculosis.

Hartkoorn Ruben C RC Ryabova Olga B OB Chiarelli Laurent R LR Riccardi Giovanna G Makarov Vadim V Cole Stewart T ST

Antimicrobial agents and chemotherapy 20140218 5

On using the streptomycin-starved 18b strain as a model for nonreplicating Mycobacterium 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 fo ...[more]

PMID: 24550336

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