Membranotropic effects of the antibacterial agent triclosan

Triclosan is a broad-spectrum hydrophobic antibacterial agent used in derma tological preparations and oral hygiene products. To gain further insight i nto the mode of action of Triclosan we examined its effects on membranes by performing leakage titrations of different oral bacteria and studying its interaction with model membranes through the use of different biophysical t echniques. There was negligible efflux of intracellular material from Strep tococcus sobrinus at the minimal inhibitory concentration of Triclosan; wha tever leakage did occur commenced only at much higher concentrations. In co ntrast, no leakage was observed at even the minimal bactericidal concentrat ion for Porphyromonas gingivalis. Triclosan decreased the onset temperature of the gel to liquid-crystalline phase transition of 1,2-dimyristoyl-sn-gl ycero-3-phosphocholine and 1,2-dimyristoyl-sn-3-[phospho-rac-glycerol] memb ranes and was immiscible with these lipids in the fluid phase at concentrat ions greater than 5 mol%. Steady-state fluorescence anisotropy measurements of different phospholipid/Triclosan samples using 3-(p-6-phenyl-1,3,5-hexa trienyl)-phenylpropionic acid were consistent with the calorimetric data. I ncorporation of increasing amounts of Triclosan into 1,2-dielaidoyl-sn-glyc ero-3-phosphoethanolamine (DEPE) vesicles induced the nonlamellar H, hexago nal phase at low temperatures and new immiscible phases at temperatures bel ow the main transition of DEPE. Taking these results together suggests that the antibacterial effects of Triclosan are mediated at least in part throu gh its membranotropic effects, resulting in destabilized structures which c ompromise the functional integrity of cell membranes without inducing cell lysis. (C) 2001 Academic Press.