Methicillin-resistant Staphylococcus aureus (MRSA) cause many severe infections. MRSA are resistant to most beta-lactams, and staphylococci have been resistant to Penicillin G since before MRSA strains evolved. Most staphylococci are able to express beta-lactamases, which degrade antibiotics, like Penicillin G. This study aims to restore the antibiotic functionality of Penicillin G against USA300 MRSA strains. USA300 can be resensitized to Penicillin G treatment using antibiotic enhancers, which could allow conservation of other antibiotic drugs. We have identified methoxyquinolines as potential enhancers of Penicillin G activity against USA300 MRSA strains. In this study, 2-(3-(1-butyl-1H-imidazol-2-yl)piperidin-1-yl)-8-methoxyquinoline and structural analogs were evaluated for functional enhancement of Penicillin G. Minimum inhibitory concentration (MIC) assays were conducted for Penicillin G activity against USA300 in the presence of each chemical. Up to 8-fold MIC reduction was observed across the screen. We plan to report the structure-function relationship for this series of chemicals. The mechanism of enhancement will be investigated by evaluating beta-lactamase expression, PBP2a inhibition, and gene knockout effects. This presentation will reveal a novel tool in our fight against antibiotic resistance.

Pièce de résistance: Reviving penicillin G against methicillin-resistant Staphylococcus aureus

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.