Lupeol as a Modulator of Bacterial Resistance Mediated by the MepA Efflux Pump in Staphylococcus aureus

Increasing bacterial resistance has stimulated the search for alternative therapeutic strategies, particularly efflux pump inhibitors, which enhance antimicrobial activity by increasing intracellular drug concentration. Natural compounds such as Lupeol have emerged as promising resistance modulators. This study investigated the ability of Lupeol to inhibit the MepA efflux pump in the K2068 strain of Staphylococcus aureus . Minimum inhibitory concentration, efflux inhibition by microdilution, membrane permeability (Sytox Green), ethidium bromide fluorescence, gene expression by RT-qPCR, and molecular docking analyses were performed. Lupeol showed no intrinsic antibacterial or cell wall activity but effectively inhibited the MepA efflux pump. Its effect on ethidium bromide fluorescence was dose-dependent, and RT-qPCR confirmed significant suppression of mepA gene expression. Molecular docking revealed strong binding affinity (− 9.010 kcal/mol) involving van der Waals, hydrophobic, and hydrogen interactions. These findings indicate that Lupeol is a promising efflux pump inhibitor with potential to combat bacterial resistance.