Sensitizing methicillin-resistant Staphylococcus aureus (MRSA) to cefuroxime: the synergic effect of bicarbonate and the wall teichoic acid inhibitor ticlopidine

• DOI: 10.1128/aac.01627-23
• Publication Date: 2024-02-13T14:01:29Z
• Authors: Selvi C. Ersoy; Richard A. Proctor; Warren E. Rose; Wessam Abdelhady; Sook-Ha Fan; Sabrina L. Madrigal; Ahmed M. Elsayed; Henry F. Chambers; Rita G. Sobral; Arnold S. Bayer
• Keywords: Ex vivo

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) strains are a major challenge for clinicians due, in part, to their resistance most β-lactams, the first-line treatment methicillin-susceptible S. . A phenotype termed “NaHCO 3 -responsiveness” has been identified, wherein many clinical MRSA isolates rendered susceptible standard-of-care β-lactams presence of physiologically relevant concentrations NaHCO , vitro and ex vivo ; moreover, such -responsive” can be effectively cleared by from target tissues experimental infective endocarditis (IE). One mechanistic impact exposure on -responsive is repress WTA synthesis. This effect mimics tarO -deficient MRSA, including sensitization PBP2-targeting β-lactam, cefuroxime (CFX). Herein, we further investigated impacts CFX susceptibility absence synthesis inhibitor, ticlopidine (TCP), collection skin soft tissue infections (SSTI) bloodstream (BSI). and/or TCP enhanced both minimum inhibitor concentration (MIC) time-kill assays, as well an simulated vegetations (SEV) model, MRSA. Furthermore, IE (presumably endogenous ), pre-exposure prior infection sensitized strain (but not non-responsive strain) clearances tissues. These data support notion that acting similarly inhibitors, inhibitors have potential translational applications certain conjunction with specific β-lactam agents.