[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
Bicarbonate Resensitization of Methicillin-Resistant Staphylococcus aureusto β-Lactam Antibiotics
Selvi C. Ersoy, Wessam Abdelhady, Liang Li, Henry F. Chambers, Yan Q. Xiong, Arnold S. Bayer
Endovascular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a major healthcare concern, especially infective endocarditis (IE). Standard antimicrobial susceptibility testing (AST) defines most MRSA strains as ‘resistant’ to β-lactams, often leading to use of costly and/or toxic treatment regimens. In this investigation, five prototype MRSA strains, representing the range of genotypes in current clinical circulation, were studied. We identified two distinct MRSA phenotypes upon AST using standard media, with or without sodium bicarbonate (NaHCO3) supplementation: one highly susceptible to the anti-staphylococcal β-lactams, oxacillin and cefazolin (‘NaHCO3-responsive’) and one resistant to such agents (‘NaHCO3-nonresponsive’). These phenotypes accurately predicted clearance profiles of MRSA from target tissues in experimental MRSA IE treated with each β-lactam. Mechanistically, NaHCO3 reduced expression of two key genes involved in the MRSA phenotype, mecA and sarA, leading to decreased production of penicillin-binding protein (PBP) 2a (that mediates methicillin resistance), in NaHCO3-responsive (but not in NaHCO3-nonresponsive) strains. Moreover, both cefazolin and oxacillin synergistically killed NaHCO3-responsive strains in the presence of the host defense antimicrobial peptide (LL-37) in NaHCO3-supplemented media. These findings suggest that AST of MRSA strains in NaHCO3-containing media may potentially identify infections caused by NaHCO3-responsive strains that are appropriate for β-lactam therapy.
Copyright © 2019 Ersoy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Keywords: Antibiotics; Drugs Resistance; MRSA; Staphylococcus aureus; Endocarditis; Bicarbonate; Oxacillin; Cefazolin; Beta-lactams.