title: Interaction of the polyene antibiotics with lipid bilayer vesicles containing cholesterol.
abstract: The interaction of the polyene antibiotics, amphotericin B, nystatin and filipin with cholesterol-containing single bilayer lipid vesicles has been characterized using gel permeation chromatography and proton magnetic resonance. All three antibiotics bind to vesicles at low concentrations without causing a large amount of vesicle destruction. The strength of binding as determined by gel permeation studies is greater for filipin and amphotericin than for nystatin. Nystatin and amphotericin B at these low concentrations induce a rapid loss of internal vesicle contents consistents consistent with pore formation. Filipin induces no leakage beyond that expected from partial vesicle destruction or general detergent action. At antibiotic levels above 1:1 antibiotic: cholesterol ratios the NMR results show all three antibiotics to cause extensive vesicle destruction. The onset of this behavior, which appears to be independent of the total antibiotic concentraion, indicates a well defined antibiotic : cholesterol interaction stoichiometry. Despite the fact that cholesterol is required for antibiotic activity, the NMR spectra prior to vesicle destruction show no changes indicative of an antibiotic-induced reversal of cholesterol restriction of phosphatidylcholine mobility. The contrast with polyene antibiotic behavior in more extended bilayers is discussed.
mesh_terms: D000666:Amphotericin B; D001665:Binding Sites; D055598:Chemical Phenomena; D002621:Chemistry; D002784:Cholesterol; D002850:Chromatography, Gel; D005372:Filipin; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D008954:Models, Biological; D008968:Molecular Conformation; D009761:Nystatin; D010713:Phosphatidylcholines; D011090:Polyenes; D013056:Spectrophotometry, Ultraviolet
chemical_list: D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D011090:Polyenes; D009761:Nystatin; D000666:Amphotericin B; D005372:Filipin; D002784:Cholesterol