Steroid Interference with Antifungal Activity of Polyene Antibiotics

Abstract

Wide differences exist among the polyene antibiotics, nystatin, rimocidin, filipin, pimaricin, and amphotericin B, with reference to steroid interference with their antifungal activities against Candida albicans. Of the numerous steroids tested, ergosterol was the only one which effectively antagonized the antifungal activity of all five polyene antibiotics. The antifungal activities of nystatin and amphotericin B were the least subject to vitiation by the addition of steroids other than ergosterol, and those of filipin, rimocidin, and pimaricin were the most sensitive to interference. Attempts to delineate the structural requirements of steroids possessing polyene-neutralizing activity in growing cultures of C. albicans are discussed. The ultraviolet absorbance of certain antibiotic steroid combinations was also studied.

Sterol‐polyene antibiotic complexation: Probe of membrane structure

“…The binding of filipin to ergosterol in vesicles is strong (Kd = 2.47 -+ 0.05, but approximately three times weaker than tbat to cholesterol) (53). This is consistent with the report that addition of cholesterol simultaneously with filipin decreases the fungicidal activity of the antibiotic more effectively than does exogenous ergosterol (54). Filipin and amphotericin B differ markedly in their ability to discriminate among sterols incorporated into vesicles, with respect to equilibrium (48,50) and kinetic (55,56) properties.…”

Antifungal Agents: Mode of Action, Mechanisms of Resistance, and Correlation of These Mechanisms with Bacterial Resistance

“…All organisms susceptible to polyenes, e.g., yeasts, algae, and protozoa, contain sterols in their outer membrane, while resistant organisms do not (97). The importance of membrane sterols for polyene activity is also supported by earlier studies, where it was shown that fungi can be protected from the inhibitory action of certain polyenes by the addition of sterol to the growth medium (41,73,159). It was suggested that this effect is due to a physicochemical interaction between added sterols and the polyenes, which prevents the drug from binding with the cellular sterols.…”

Nystatin-Resistant Mutants of Yeast: Alterations in Sterol Content

“…Ergosterol is the major membrane sterol in yeast 4 (9) and binds nystatin and other polyenes effectively (15). Absence or severe reduction in the amount of ergosterol in the membrane and its .3 ./\ z\< nyslc replacement with sterols which bind nystatin less effectively is a predictable mechanism for the nys \ a X II Uorigin of resistance.…”