Membranotropic effects of the antibacterial agent Triclosan.
Triclosan is a broad-spectrum hydrophobic antibacterial agent used in dermatological preparations and oral hygiene products. To gain further insight into 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 techniques. There was negligible efflux of intracellular material from Streptococcus sobrinus at the minimal inhibitory concentration of Triclosan; whatever leakage did occur commenced only at much higher concentrations. In contrast, no leakage was observed at even the minimal bactericidal concentration for Porphyromonas gingivalis. Triclosan decreased the onset temperature of the gel to liquid-crystalline phase transition of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-3-[phospho-rac-glycerol] membranes and was immiscible with these lipids in the fluid phase at concentrations greater than 5 mol%. Steady-state fluorescence anisotropy measurements of different phospholipid/Triclosan samples using 3-(p-6-phenyl-1,3,5-hexatrienyl)-phenylpropionic acid were consistent with the calorimetric data. Incorporation of increasing amounts of Triclosan into 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE) vesicles induced the nonlamellar H(II) hexagonal phase at low temperatures and new immiscible phases at temperatures below the main transition of DEPE. Taking these results together suggests that the antibacterial effects of Triclosan are mediated at least in part through its membranotropic effects, resulting in destabilized structures which compromise the functional integrity of cell membranes without inducing cell lysis.
Villalaín
J
J
Centro de Biología Molecular y Celular, Universidad Miguel Hernández, E-03202 Elche (Alicante), Spain.
Mateo
C R
CR
Aranda
F J
FJ
Shapiro
S
S
Micol
V
V
D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects*; D005454:Fluorescence Polarization; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry; D008567:Membranes, Artificial; D009055:Mouth / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000737:chemistry / Q000187:drug effects*; D016986:Streptococcus sobrinus / Q000737:chemistry / Q000187:drug effects*; D014260:Triclosan / Q000494:pharmacology*; D014961:X-Ray Diffraction
D000891:Anti-Infective Agents, Local; D008563:Membrane Lipids; D008567:Membranes, Artificial; D014260:Triclosan