In silico and in vitro screening of selected antimicrobial compounds for inhibiting drug efflux pumps to combat threatening MRSA

The rapid emergence of antibiotic-resistant bacteria is occurring worldwide due to severe antibiotic abuse in the past few decades; among them, Methicillin-resistant Staphylococcus aureus (MRSA) is of major concern. Study examines potent antimicrobial compounds against Methicillin resistance Staphylococcus aureus (MRSA) efflux system. Interactome data serves as a primary focal point for global MRSA infection control initiatives. We employed CB Dock and Discovery Studio for performing docking analysis on specific antimicrobial compounds against NorA, NorB, and NorG. Additionally, we conducted molecular dynamics simulations using myPresto. In vitro validation was done by agar-based EtBr cartwheel method to assess the efflux pump activity of MRSA. Out of the eight screened antimicrobial compounds, quercetin exhibited favorable binding energies. Subsequently, molecular dynamics simulations were conducted on quercetin complexes with NorA, NorB, and NorG. In vitro result revealed that the quercetin is active at concentration of 60 µg/ml ±10 against MRSA to inhibit efflux mechanisms. Quercetin demonstrated the most promising binding affinity with the efflux pumps and their regulators of MRSA, making it the prime candidate for use with antibiotics. In-vivo experiments must be performed to validate the in-silico and in vitro analysis. [Display omitted] •Antibiotic resistance is a major global issue caused by overuse of antibiotics.•Researchers are developing new antimicrobials, including phytochemicals to fight against AMR.•Quercetin, a phytochemical with highest efflux pump affinity, is a promising anti-MRSA agent.