title: Competitive binding of cholesterol and ergosterol to the polyene antibiotic nystatin. A fluorescence study.
abstract: Competition studies between cholesterol and ergosterol were carried out to gain insight into the binding interactions between nystatin and these sterols. Lipid vesicles were prepared with mixtures of palmitoyloleoylphosphocholine/ergosterol/cholesterol, and both sterol molar ratio and total content were varied. The inhibitory effect of cholesterol toward the ergosterol ability to induce the formation of long-lived fluorescent antibiotic species was used to detect nystatin-cholesterol interactions. It was found that the key factor controlling nystatin photophysical properties in the ternary lipid mixtures was their ergosterol/cholesterol molar ratio and not their overall sterol content. Moreover, permeabilization studies showed that nystatin was able to form pores in all the mixed vesicles, but the initial rate of pore formation was also dependent on the ergosterol/cholesterol molar ratio. Our data show that ergosterol is displaced by competing cholesterol, indirectly confirming cholesterol's ability to coassemble with nystatin. The distinct spectroscopic properties emphasize the different molecular architecture adopted by nystatin-cholesterol and -ergosterol complexes, and therefore are relevant to understanding the interaction of the antibiotic with membranes.
authors.affiliation: CQFM, Instituto Superior Técnico, Lisbon, Portugal.
authors.forename: Liana
authors.initials: L
authors.lastname: Silva
authors.forename: Ana
authors.initials: A
authors.lastname: Coutinho
authors.forename: Alexander
authors.initials: A
authors.lastname: Fedorov
authors.forename: Manuel
authors.initials: M
authors.lastname: Prieto
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001665:Binding Sites; D002784:Cholesterol / Q000737:chemistry*; D004875:Ergosterol / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry; D009761:Nystatin / Q000737:chemistry*; D011090:Polyenes / Q000737:chemistry; D013050:Spectrometry, Fluorescence
chemical_list: D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D008081:Liposomes; D046911:Macromolecular Substances; D011090:Polyenes; D009761:Nystatin; D002784:Cholesterol; D004875:Ergosterol