Interaction of polyene antibiotics with membrane lipids: physicochemical studies of the molecular basis of selectivity.

From various studies on the interaction of amphotericin B with unilamellar lipid vesicles, it appears that the strength of the binding does not depend only on the presence of sterol molecules in the membranes; and that several bound amphotericin B species are in competition, their relative amounts depending on the nature and percentage of sterol in the lipid bilayer. Bound amphotericin B molecules exchange rapidly between the membranes. It is therefore possible to add the antibiotic by transfer from amphotericin B-preloaded vesicles of dipalmitoylphosphatidylcholine, instead of direct addition. In these conditions the selectivity in the sensitivity to H+ leakage induced by amphotericin B between ergosterol- and cholesterol-containing vesicles is greatly enhanced. In the case of Mycoplasma laidlawii cells, a preliminary increase of K+ cellular content is observed when low doses of amphotericin B are added by transfer, an effect which is not observed with direct addition of the antibiotic.