Inhibition of Staphylococcus pseudintermedius Efflux Pumps by Using Staphylococcus aureus NorA Efflux Pump Inhibitors

• Published in: Antibiotics (Basel) Vol. 12; no. 5; p. 806
• Main Authors: Rampacci, Elisa, Felicetti, Tommaso, Cernicchi, Giada, Stefanetti, Valentina, Sabatini, Stefano, Passamonti, Fabrizio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.04.2023; MDPI
• Subjects: Antibiotic resistance; antibiotic resistance breakers; Antibiotics; Antimicrobial agents; antimicrobial resistance; Bacteria; Bacterial infections; Biofilms; Biological activity; Chlorhexidine; Ciprofloxacin; Dihydropyridine; Dogs; Drug resistance; Efflux; efflux pump inhibitors; Ethidium bromide; Gentamicin; Inhibitors; NorA; Optimization; Pathogens; Pharmaceutical sciences; Quinoline; Staphylococcus aureus; Staphylococcus infections; Staphylococcus pseudintermedius; Synergism; Synergistic effect; new antibiotics; NorA; antimicrobial resistance; Staphylococcus pseudintermedius; antibiotic resistance breakers; Staphylococcus aureus; efflux pump inhibitors
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics12050806

One promising approach in treating antibiotic-resistant bacteria is to "break" resistances connected with antibacterial efflux by co-administering efflux pump inhibitors (EPIs) with antibiotics. Here, ten compounds, previously optimized to restore the susceptibility to ciprofloxacin (CIP) of -overexpressing , were evaluated for their ability to inhibit -mediated efflux in and synergize with CIP, ethidium bromide (EtBr), gentamycin (GEN), and chlorhexidine digluconate (CHX). We focused efforts on as a pathogenic bacterium of concern within veterinary and human medicine. By combining data from checkerboard assays and EtBr efflux inhibition experiments, the hits 2-arylquinoline , dihydropyridine and 2-phenyl-4-carboxy-quinoline were considered the best EPIs for . Overall, most of the compounds, except for 2-arylquinoline compound , were able to fully restore the susceptibility of to CIP and synergize with GEN as well, while the synergistic effect with CHX was less significant and often did not show a dose-dependent effect. These are valuable data for medicinal chemistry optimization of EPIs for and lay the foundation for further studies on successful EPIs to treat staphylococcal infections.