Lipid composition and dynamics of cell membranes of Bacillus stearothermophilus adapted to amiodarone

Bacillus stearothermophilus, a useful model to evaluate membrane interactio ns of lipophilic drugs, adapts to the presence of amiodarone in the growth medium. Drug concentrations in the range of 1-2 mu M depress growth and 3 m u M completely suppresses growth. Adaptation to the presence of amiodarone is reflected in lipid composition changes either in the phospholipid classe s or in the acyl chain moieties. Significant changes are observed at 2 mu M and expressed by a decrease of phosphatidylethanolamine (relative decrease of 23.3%) and phosphatidylglycerol (17.9%) and by the increase of phosphog lycolipid (162%). The changes in phospholipid acyl chains are expressed by a decrease of straight-chain saturated fatty acids (relative decrease of 12 .2%) and anteiso-acids (22%) with a parallel increase of the iso-acids (9.8 %). Consequently, the ratio straight-chain/branched iso-chain fatty acids d ecreases from 0.38 (control cultures) to 0.30 (cultures adapted to 2 mu M a miodarone). The physical consequences of the lipid composition changes indu ced by the drug were studied by fluorescence polarization of diphenylhexatr iene and diphenylhexatriene-propionic acid, and by differential scanning ca lorimetry. The thermotropic profiles of polar lipid dispersions of amiodaro ne-adapted cells are more similar to control cultures (without amiodarone) than those resulting from a direct interaction of the drug with lipids, i.e ., when amiodarone was:added directly to liposome suspensions. It is sugges ted that lipid composition changes promoted by amiodarone occur as adaptati ons to drug tolerance, providing the membrane with physico-chemical propert ies compatible with membrane function, counteracting the effects of the dru g. (C) 2000 Elsevier Science B.V. All rights reserved.