Selection for Resistant Mutants to Tobramycin and Triclosan in Biofilm Growing Pseudomonas

Adaptive resistance is a phenotypic response that allows P. aeruginosa to transiently survive aminoglycosides such as tobramycin. To date, few compounds have been identified that target adaptive resistance. We found the protonophore uncoupler triclosan disrupts the membrane potential of P. aeruginosa. The depletion of the membrane potential reduces efflux pump activity, which is essential for adaptive resistance, leading to increased tobramycin accumulation and a shorter onset of action. By selecting for resistant mutants to tobramycin and triclosan, we were able to determine that tobramycin is the agent responsible for killing when using this combination.