Action Mechanism of Polyene Antibiotics

Comparison between Amphotericin B and Its Methyl Ester

Abstract

The actions of amphotericin B and its methyl ester on liposomes were studied using various techniques, absorption spectrum, release of glucose and spin labeling. Liposomes were prepared from egg yolk phosphatidylcholine (egg PC), egg PC/cholesterol or egg PC/ergosterol. Absorption spectra of these amphotericins were changed by the addition of sterol-containing liposomes. The spectrum of amphotericin B methyl ester was also changed by the addition of egg PC liposomes. Greatly enhanced release of glucose from liposomes was observed in egg PC and egg PC/ergosterol liposmes in the presence of amphotericin B methyl ester, while amphotericin B induced the release from the sterol-containing liposomes. The effects on fluidity were examined using stearic acid spin probe. Both amphotericins decreased the membrane fluidity significantly in every liposomal system, egg PC, egg PC/cholesterol and egg PC/ergosterol. And amphotericin B methyl ester remarkably decreased the fluidity of egg PC/ergosterol liposomes. These results suggest that the methyl esterification of amphotericin B alters the physical properties of this polyene antibiotic. Amphotericin B methyl ester interacts with ergosterol-containing liposomes more preferentially than cholesterol-containing ones, while amphotericin B does not show such preference for the ergosterol-containing liposomes.