Lack of Specificity of Phenotypic Screens for Inhibitors of the Mycobacterium tuberculosis FAS-II System.
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.
['Grzegorzewicz|Anna E|AE|', 'Lelièvre|Joël|J|', 'Esquivias|Jorge|J|', 'Angala|Bhanupriya|B|', 'Liu|Jiuyu|J|', 'Lee|Richard E|RE|', 'McNeil|Michael R|MR|', 'Jackson|Mary|M|0000-0002-9212-0258']
D001426:Bacterial Proteins D054889:Fatty Acid Synthase, Type II D009169:Mycobacterium tuberculosis D009171:Mycolic Acids
phenotypic screening Mycobacterium tuberculosis FAS-II (3R)-hydroxyacyl-ACP dehydratase drug development mycolic acids β-ketoacyl synthase