Bakker_2023_J.Am.Chem.Soc_145_1136

Reference

Title : Chemical Proteomics Reveals Antibiotic Targets of Oxadiazolones in MRSA - Bakker_2023_J.Am.Chem.Soc_145_1136
Author(s) : Bakker AT , Kotsogianni I , Mirenda L , Straub VM , Avalos M , van den Berg R , Florea BI , van Wezel GP , Janssen APA , Martin NI , van der Stelt M
Ref : Journal of the American Chemical Society , 145 :1136 , 2023
Abstract :

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.

PubMedSearch : Bakker_2023_J.Am.Chem.Soc_145_1136
PubMedID: 36584241
Gene_locus related to this paper: staa3-q2fkj0 , staau-MW0741 , staau-MW2456 , staau-SA1143 , staau-SA2367 , staau-SAV0321 , staau-SAV0655

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Citations formats

Bakker AT, Kotsogianni I, Mirenda L, Straub VM, Avalos M, van den Berg R, Florea BI, van Wezel GP, Janssen APA, Martin NI, van der Stelt M (2023)
Chemical Proteomics Reveals Antibiotic Targets of Oxadiazolones in MRSA
Journal of the American Chemical Society 145 :1136

Bakker AT, Kotsogianni I, Mirenda L, Straub VM, Avalos M, van den Berg R, Florea BI, van Wezel GP, Janssen APA, Martin NI, van der Stelt M (2023)
Journal of the American Chemical Society 145 :1136