Triclosan depletes the membrane potential in Pseudomonas aeruginosa biofilms inhibiting aminoglycoside induced adaptive resistance
Fig 7
Triclosan sensitizes P. aeruginosa to tobramycin by acting as a protonophore, inhibiting efflux pump activity, and abolishing adaptive resistance.
(1) Within 2-hrs of exposure to tobramycin, adaptive resistance occurs, (2) which is due to the induction of RND-type efflux pumps and surge in membrane potential (Δѱ), resulting in reduced accumulation of tobramycin within the cytosol. (3) Triclosan shuttles protons across the inner membrane, collapsing the proton motive force (Δp) and depolarizing the Δѱ. Consequently, efflux pump activity is reduced and there is enhanced accumulation of tobramycin within the cytosol. Finally, tobramycin binds to the A-site of the ribosome, corrupting protein synthesis and causing membrane permeabilization. Overall, triclosan accelerates and increase the effectiveness of tobramycin by reducing the Δѱ and efflux pump activity. Proton gradient, ΔpH. Outer membrane protein (OMP), membrane fusion protein (MFP), inner membrane protein (IMP).