Abstract
Biofilm-based infections are difficult to treat due to their inherent resistance to antibiotic treatment. Discovering new approaches to enhance antibiotic efficacy in biofilms would be highly significant in treating many chronic infections. Exposure to aminoglycosides induces adaptive resistance in Pseudomonas aeruginosa biofilms. Adaptive resistance is primarily the result of active antibiotic export by RND-type efflux pumps, which use the proton motive force as an energy source. We show that the protonophore uncoupler triclosan depletes the membrane potential of biofilm growing P. aeruginosa, leading to decreased activity of RND-type efflux pumps. This disruption results in increased intracellular accumulation of tobramycin and enhanced antimicrobial activity in vitro. In addition, we show that triclosan enhances tobramycin effectiveness in vivo using a mouse wound model. Combining triclosan with tobramycin is a new anti-biofilm strategy that targets bacterial energetics, increasing the susceptibility of P. aeruginosa biofilms to aminoglycosides.