Effects of (+)-totarol, a diterpenoid antibacterial agent, on phospholipid model membranes.
(+)-Totarol, a highly hydrophobic diterpenoid isolated from Podocarpus spp., is inhibitory towards the growth of diverse bacterial species. (+)-Totarol decreased the onset temperature of the gel to liquid-crystalline phase transition of DMPC and DMPG membranes and was immiscible with these lipids in the fluid phase at concentrations greater than 5 mol%. Different (+)-totarol/phospholipid mixtures having different stoichiometries appear to coexist with the pure phospholipid in the fluid phase. At concentrations greater than 15 mol% (+)-totarol completely suppressed the gel to liquid-crystalline phase transition in both DMPC and DMPG vesicles. Incorporation of increasing amounts of (+)-totarol into DEPE vesicles induced the appearance of the H(II) hexagonal phase at low temperatures in accordance with NMR data. At (+)-totarol concentrations between 5 and 35 mol% complex thermograms were observed, with new immiscible phases appearing at temperatures below the main transition of DEPE. Steady-state fluorescence anisotropy measurements showed that (+)-totarol decreased and increased the structural order of the phospholipid bilayer below and above the main gel to liquid-crystalline phase transition of DMPC respectively. The changes that (+)-totarol promotes in the physical properties of model membranes, compromising the functional integrity of the cell membrane, could explain its antibacterial effects.
Micol
V
V
Centro de Biologia Molecular y Celular, Universidad Miguel Hernandez, E-0302 Elche, Spain.
Mateo
C R
CR
Shapiro
S
S
Aranda
F J
FJ
Villalaín
J
J
D045784:Abietanes; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D004134:Dimyristoylphosphatidylcholine; D004224:Diterpenes / Q000494:pharmacology*; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010715:Phosphatidylglycerols; D013696:Temperature; D014961:X-Ray Diffraction
D045784:Abietanes; D000890:Anti-Infective Agents; D004224:Diterpenes; D008051:Lipid Bilayers; D010715:Phosphatidylglycerols; C078548:totarol; C002773:dimyristoylphosphatidylglycerol; D004134:Dimyristoylphosphatidylcholine