Effects of (+)-totarol, a diterpenoid antibacterial agent, on phospholipidmodel membranes

(+)-Totarol, a highly hydrophobic diterpenoid isolated from Podocarpus spp. , is inhibitory towards the growth of diverse bacterial species. (+)-Totaro l decreased the onset temperature of the gel to liquid-crystalline phase tr ansition of DMPC and DMPG membranes and was immiscible with these lipids in the fluid phase at concentrations greater than 5 mol%. Different (+)-totar ol/phospholipid mixtures having different stoichiometries appear to coexist with the pure phospholipid in the fluid phase. At concentrations greater t han 15 mol% (+)-totarol completely suppressed the gel to liquid-crystalline phase transition in both DMPC and DMPG vesicles. Incorporation of increasi ng 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 obs erved, with new immiscible phases appearing at temperatures below the main transition of DEPE. Steady-state fluorescence anisotropy measurements showe d that (+)-totarol decreased and increased the structural order of the phos pholipid bilayer below and above the main gel to liquid-crystalline phase t ransition of DMPC respectively. The changes that (+)-totarol promotes in th e physical properties of model membranes, compromising the functional integ rity of the cell membrane, could explain its antibacterial effects. (C) 200 1 Elsevier Science B.V. All rights reserved.