Interaction of polyene antibiotics with single and mixed lipid monomolecular layers

Abstract

1. 1. Etruscomycin, amphotericin B, and pimaricin preferentially interact with cholesterol, and not with lecithin, monolayers at low molar ratios of antibiotic/lipid. Similar results have been previously reported for filipin and nystatin. At initial surface pressures above the collapse pressures of the antibiotics, the ability of the polyenes to increase the surface pressure of a cholesterol monolayer is in the order: filipin > etruscomycin > amphotericin B > pimaricin > nystatin. These observations suggest that the ability of the polyene antibiotics to cause membrane damage may be correlated with their affinity for sterol. Derivatives of filipin, which have little or no biological activity, also prduce a much weaker interaction with cholesterol monolayers than the parent antibiotic.

2. 2. In mixed monolayers of lecithin and cholesterol, the surface pressure increase obtained with filipin is diminished as the relative content of the phospholipid is raised. This observation supports previous studies indicating that the polyene sensitivity of a membrane may be dependent on the phospholipid/sterol ratio and not on the presence of sterol per se. 3. 3. Filipin, nystatin and pimaricin can interact with monolayers of lecithin (in the absence of cholesterol) at high molar ratios of antibiotic/lipid. These observations are consistent with the results of eSessa W Weissmann that some of the polyenes can release markers from liposomes prepared with lecithin alone. Past and present experiments suggest that interaction between the polyenes and membrane phospholipid is probably without significance as regards the antifungal and hemolytic activity of the antibiotics. At high molar ratios, filipin can also increase the surface pressure of oleic acid monolayers. These results are in accord with several reports indicating that addition of fatty acids, as well as phospholipids, to the medium can antagonize the growth inhibitory and lytic properties of the polyenes. 4. 4. Filipin has only a slight effect on the surface pressure of cholesterol acetate monolayers, which is consistent with the view that a free hydroxyl group is necessary for interaction with the polynees. This conclusion is supported by the fining that filipin can also interact with monolayers of cetyl alcohol at low molar ratios of antibiotic/lipid. The inhibitory influence of urea suggests that hydrogen bond formation may play an important role in polyene sterol—interaction.