Location and orientation of Triclosan in phospholipid model membranes.
Triclosan is a hydrophobic antibacterial agent used in dermatological preparations and oral hygiene products. Although the molecular mechanism of action of this molecule has been attributed to inhibition of fatty acid biosynthesis, earlier work in our laboratories strongly suggested that the antibacterial action of Triclosan is mediated at least partly through its membranotropic effects. In order to assess its location in phospholipid membranes, high-resolution magic-angle spinning natural abundance (13)C NMR of Triclosan embedded within egg yolk lecithin model membranes has been used to obtain (13)C spin-lattice relaxation times for both Triclosan and lecithin carbon atoms in the presence of Gd(3+ )ions. The results indicate that Triclosan is localized in the upper region of the phospholipid membrane, its hydroxyl group residing in the vicinity of the C = O/C2 carbon atoms of the acyl chain of the phospholipid, and the rest of the Triclosan molecule is probably aligned in a nearly perpendicular orientation with respect to the phospholipid molecule. Intercalation of Triclosan into bacterial cell membranes likely compromises the functional integrity of those membranes, thereby accounting for at least some of this compound's antibacterial effects.
Guillén
Jaime
J
Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, 03202 Elche-Alicante, Spain.
Bernabeu
Angela
A
Shapiro
Stuart
S
Villalaín
José
J
D000465:Algorithms; D004530:Egg Yolk / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008560:Membrane Fluidity; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry*; D008567:Membranes, Artificial; D010713:Phosphatidylcholines / Q000032:analysis / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D011487:Protein Conformation; D014018:Tissue Distribution; D014260:Triclosan / Q000032:analysis / Q000737:chemistry*
D008565:Membrane Proteins; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D010743:Phospholipids; D014260:Triclosan