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American Society for Microbiology, Antimicrobial Agents and Chemotherapy, 5(58), p. 2944-2947, 2014

DOI: 10.1128/aac.02693-13

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Mechanism of Action of 5-Nitrothiophenes against Mycobacterium tuberculosis

Journal article published in 2014 by Ruben C. Hartkoorn, Olga B. Ryabova, Laurent R. Chiarelli ORCID, Giovanna Riccardi, Vadim Makarov, Stewart T. Cole
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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 F 420 cofactor. Furthermore, 5-nitrothiophenes were shown to be activated by the F 420 -dependent nitroreductase Ddn and to release nitric oxide, a mechanism of action identical to that described for nitroimidazoles.