Catechin gallates inhibit multidrug resistance (MDR) in Staphylococcus aureus

Abstract Epicatechin gallate (1) and epigallocatechin gallate (2) were evaluated for their antibacterial and efflux inhibitory activity against a wild-type and three multidrug-resistant (MDR) strains of STAPHYLOCOCCUS AUREUS. Compound 2 was more active than 1 based on minimum inhibitory concentrations (MICs; 32 - 64 versus 64 - > 512 μg/mL, respectively). When incorporated into the growth medium at 20 μg/mL, both compounds exhibited a four-fold potentiation of the activity of norfloxacin against a norfloxacin-resistant strain of S. AUREUS overexpressing the NorA multidrug efflux pump. Against this strain 1 was moderately more potent than 2 as an inhibitor of ethidium efflux, but at ≤ 20 μM both compounds paradoxically stimulated efflux. This phenomenon has not been encountered previously in the analysis of inhibitors of multidrug efflux.