ABSTRACT
Phenotypic screening of inhibitors of the essential Mycobacterium tuberculosis FAS-II dehydratase HadAB led to the identification of GSK3011724A, a compound previously reported to inhibit the condensation step of FAS-II. Whole-cell-based and cell-free assays confirmed the lack of activity of GSK3011724A against the dehydratase despite evidence of cross-resistance between GSK3011724A and HadAB inhibitors. The nature of the resistance mechanisms is suggestive of alterations in the FAS-II interactome reducing access of GSK3011724A to KasA.
FOOTNOTES
- Received 4 September 2020.
- Returned for modification 20 October 2020.
- Accepted 26 October 2020.
- Accepted manuscript posted online 2 November 2020.
Supplemental material is available online only.
- Copyright © 2020 American Society for Microbiology.
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