行动方式
化学
蛋白质组学
抗生素
计算生物学
抗菌剂
金黄色葡萄球菌
抗菌活性
抗生素耐药性
生物化学
细菌
遗传学
生物
基因
有机化学
作者
Alexander T Bakker,Ioli Kotsogianni,Liza Mirenda,Verena M Straub,Mariana Ávalos,Richard J. B. H. N. van den Berg,Bogdan I. Florea,Gilles P. van Wezel,A. M. Janssen,Nathaniel I. Martin,Mario van der Stelt
摘要
Phenotypic screening is a powerful approach to identify novel antibiotics, but elucidation of the targets responsible for the antimicrobial activity is often challenging in the case of compounds with a polypharmacological mode of action. Here, we show that activity-based protein profiling maps the target interaction landscape of a series of 1,3,4-oxadiazole-3-ones identified in a phenotypic screen to have high antibacterial potency against multidrug-resistant Staphylococcus aureus. In situ competitive and comparative chemical proteomics with a tailor-made activity-based probe, in combination with transposon and resistance studies, revealed several cysteine and serine hydrolases as relevant targets. Our data showcase oxadiazolones as a novel antibacterial chemotype with a polypharmacological mode of action, in which FabH, FphC, and AdhE play a central role.
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