Effect of fatty acids on action of polyene antibiotics

Abstract

Fatty acids cause a decrease in the absorption spectra of the antifungal polyene macrolide antibiotics nystatin, filipin, candicidin, and amphotericin B. For nystatin, fi6pin, and candicidin, this decrease in absorption could be correlated with the activity of the fatty acids in protecting the yeast Saccharomyces cerevisiae against the action of these antibiotics. With amphotericin B a correlation was observed between the decrease in absorption caused by certain derivatives of fatty acids and the protective action of these derivatives against the activity of amphotericin B on yeast. It is concluded that, like the sterols, fatty acids also interact with the polyene antibiotics and thereby reduce their effective concentrations.The polyene macrolide antibiotics are effective antifungal agents and, as a rule, are inactive against bacteria. The polyenes interact with sterols of the cell membrane to alter its structure and cause the leakage of essential metabolites (see reference 3). Lampen et al. (6) showed that when ergosterol or cholesterol was incorporated into the culture medium, yeasts were protected from the action of polyenes such as filipin, nystatin, and antimycoin.Hickey (5) has shown that the action of the polyene ascosin on the yeast Saccharomyces cerevisiae was antagonized by fatty acids, the longer-chain-length acids and the more unsaturated acids being the most effective. Ghosh and Ghosh (2), investigating the effect of various lipids on the uptake of nystatin by Candida albicans, found that the uptake was antagonized more effectively by linoleic acid than by ergosterol, cholesterol, vitamin A, or oleic acid. Sarachek and Higgins (8) showed that fatty acids could protect nonirradiated cells from damage by amphotericin B and also significantly enhance the recovery of ultraviolet light-damaged cells. The protective action increased with chain length, but the unsaturated C18 acids, oleic, linoleic, and linolenic, were less effective than saturated C18 stearic acid. Recently, Hammond and Kliger (4) showed that resistance to membrane damage of C. albicans by candicidin increased with the age of the culture. This effect was correlated with an increase in cell wall triglycerides with age. Lampen et al. (6) studied the binding of the polyene antibiotics filipin, nystatin, and antimycoin to sterols by spectrophotometric means. They found that sterols significantly reduced the absorbance of the polyenes at their absorption maxima. This was interpreted to mean that the sterols decreased the effective concentration of the polyenes in the mixture. This was borne out by the fact that the addition of isopropyl alcohol restored the absorbance because of the resolubilization of the polyenes. Bittman and Fischkoff (1), by fluorescence studies, concluded that polyene-cholesterol binding did take place in an aqueous buffer and that the binding was accomplished by hydrophobic interactions.A study was made to determine whether changes in the absorbance of polyene antibiotics could be produced by fatty acids and whether t...

Amphotericin B Resistance and Membrane Fluidity in Kluyveromyces lactis Strains

“…This antifungal agent possesses a hydrophobic part (hydrocarbon chain) and a hydrophilic part (polyhydroxyl chain); its amphipathic properties allow interactions with the membrane after diffusion through the yeast cell wall. Its interaction with membrane constituents (14,16,18) provokes the formation of pores responsible for several reactions, such as lipid oxidations and peroxidations, inhibition of membrane enzymes (3, 4), osmotic shocks, and, finally, cell death (32).…”

Lipids of Candida albicans

“…Stationary phase cells were more resistant to polyene action than a younger population of cells, and again this variation was not associated with any change in the sterol content [49). The protective effect of fatty acids towards polyene action is also reported by several other investigators [29,38,78]. It appears that fatty acids interact with polyene antibiotics, thus reducing their effective concentrations [38].…”

“…The protective effect of fatty acids towards polyene action is also reported by several other investigators [29,38,78]. It appears that fatty acids interact with polyene antibiotics, thus reducing their effective concentrations [38].…”

Capric acid secreted by Saccharomyces boulardii influences the susceptibility of Candida albicans to fluconazole and amphotericin B

“…Free FAs have been previously reported to directly interact with AMB and inhibit its antifungal activity 39 . Such a relationship has been described so far for myristic, palmitic and stearic acids 39 .…”