Catechin gallates inhibit multidrug resistance (MDR) in Staphylococcus aureus

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 mug/mL, respectively). When incorporated into the growth medium at 20 mug/mL, both compounds exhibited a fourfold 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 less than or equal to20 muM both compounds paradoxically stimulated efflux. This phenomenon has not been encountered previously in the analysis of inhibitors of multidrug efflux.