MECHANISM OF PROTECTION BY STEROLS AGAINST POLYENE ANTIBIOTICS

Abstract

Previous reports that sterols prevent the antifungal activity of polyene antibiotics (filipin, nystatin, and antimycoin) were confirmed. Sterols, however, did not reverse an existing metabolic inhibition effected by the polyenes. It was also noted that washing yeast cells free of the antibiotic was as effective as the addition of sterols in causing a resumption of growth. Cholesterol reduced the absorption of nystatin by Saccharomyces cerevisiae. This reduction in absorption appears adequate to account for the protective effects obtained when sterols were present. The addition of sterol to an aqueous colloidal suspension of a polyene reduced the absorption of the polyene, indicating a lowered solubility and thus a lower effective concentration. These changes were reversed when isopropanol was added to the mixtures to produce complete solution of the antibiotic. The sterols did not increase the destruction of the polyenes, in fact, during long incubations there was an actual protection. Cholesterol and ergosterol protected yeast growth or metabolism and produced major spectral shifts. Cortisone, cholesterol acetate, [DELTA]-4-choles-terone, testosterone and progesterone did not protect yeast from the polyenes and produced only minor spectral changes. It is suggested that a physico-chemical interaction of polyene and sterol may reduce the effective concentration of the antibiotic and thus protect the organism. This would be analogous to the detoxication of plant saponins (e.g., digitonin) by sterols.