Efflux Pumps Might Not Be the Major Drivers of QAC Resistance in Methicillin‐Resistant Staphylococcus aureus

• Published in: Chembiochem : a European journal of chemical biology Vol. 18; no. 16; pp. 1573 - 1577
• Main Authors: Jennings, Megan C., Forman, Megan E., Duggan, Stephanie M., Minbiole, Kevin P. C., Wuest, William M.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 17.08.2017
• Subjects: Ammonium; Ammonium compounds; Anti-Infective Agents, Local - pharmacokinetics; Anti-Infective Agents, Local - pharmacology; Antiseptics; Bacteria; Bacterial Proteins - genetics; Benzalkonium Compounds - pharmacokinetics; Benzalkonium Compounds - pharmacology; Carbonyl Cyanide m-Chlorophenyl Hydrazone - pharmacology; Cell Membrane Permeability; Concentration (composition); Drug resistance; Drug Resistance, Multiple, Bacterial - drug effects; Efflux; Membrane composition; Membrane Transport Modulators - pharmacology; Membrane Transport Proteins - genetics; Methicillin; methicillin-resistant Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus - classification; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; Minimum inhibitory concentration; Pumps; qac; quaternary ammonium compound; Quaternary ammonium compounds; Repressor Proteins - genetics; Reserpine - pharmacology; resistance; Staphylococcus infections; Uncoupling Agents - pharmacology; quaternary ammonium compound; methicillin-resistant Staphylococcus aureus; qac; resistance
• ISSN: 1439-4227; 1439-7633; 1439-7633
• DOI: 10.1002/cbic.201700233

Quaternary ammonium compounds (QACs) are commonly used antiseptics that are now known to be subject to bacterial resistance. The prevalence and mechanisms of such resistance, however, remain underexplored. We investigated a variety of QACs, including those with multicationic structures (multiQACs), and the resistance displayed by a variety of Staphylococcus aureus strains with and without genes encoding efflux pumps, the purported main driver of bacterial resistance in MRSA. Through minimum inhibitory concentration (MIC)‐, kinetic‐, and efflux‐based assays, we found that neither the qacR/qacA system present in S. aureus nor another efflux pump system is the main reason for bacterial resistance to QACs. Our findings suggest that membrane composition could be the predominant driver that allows CA‐MRSA to withstand the assault of conventional QAC antiseptics. Pièce de résistance: We describe herein our efforts to better understand the role that qac efflux genes play in biocide resistance through the implementation of our multiQAC chemical library. We identified that membrane composition, and not qac efflux, could be the predominant driver of resistance in community‐acquired methicillin‐resistant Staphylococcus aureus (CA‐MRSA).