bioRxivPharmacology & ToxicologyPreprint
A benzoxazolylurea inhibits VraS and enhances antimicrobials against vancomycin intermediate-resistant Staphylococcus aureus
A. Sarkar, M. H. Abdelaziz, E. P. Heckler, L. Ali, B. Cagle-White, S. Bhattarai, N. Smith, R. A. Coover
Abstract
Vancomycin intermediate-resistant Staphylococcus aureus (VISA) is a pathogen of concern. VraS, a histidine kinase, facilitates the VISA phenotype. Here, we reveal a benzoxazolylurea that directly inhibits VraS and enhances vancomycin to below the clinical breakpoint against an archetypal VISA strain. To the best of our knowledge, this is the first direct VraS inhibitor ever reported that shows significant enhancement of vancomycin against VISA.
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