Enhancing antibiotic activity: a strategy to control Acinetobacter infections

The emergence of antibiotic resistance has seriously diminished antibiotic efficacy and an increasing number of infections are becoming difficult to treat. One approach to the restoration of antibiotic activity is to administer them in conjunction with non-antibiotic compounds that depress resistance mechanisms. We describe the activity of ellagic and tannic acids as adjuvants that enhance the activity of aminocoumarin antibiotics against multidrug-resistant (MDR) Acinetobacter baumannii. Adjuvant activity of plant phenolics was tested using growth inhibition assays in combination with subinhibitory concentrations of novobiocin. The antibacterial susceptibilities of susceptible and MDR A. baumannii to a variety of antibiotics were determined in the absence and presence of ellagic and tannic acids. The effect of the adjuvants on bacterial outer membrane function was examined by using the fluorescence dye 1-N-phenylnaphthylamine (NPN). The efflux pump inhibition was measured by the intracellular accumulation of ethidium bromide (EtBr) and pyronin Y. At 40 mu M, ellagic and tannic acids enhanced the activity of novobiocin, coumermycin, chlorobiocin, rifampicin and fusidic acid against A. baumannii. There were no increases in the uptake of NPN or in the accumulation of EtBr after strains were treated with these adjuvants; however, the intracellular accumulation of pyronin Y by the treated cells was significantly increased, suggesting that ellagic and tannic acids act as efflux pump inhibitors. Susceptibility of MDR A. baumannii to a variety of antibiotics was enhanced in the presence of ellagic and tannic acids. The use of such plant compounds might provide effective treatments for resistant Gram-negative bacterial infections.