Effect of polyene antibiotics on phospholipid spherules containing varying amounts of charged components

Abstract

Polyene antibiotics, such as filipin, nystatin, and amphotericin B, alter the gross permeability to previously captured anions or glucose of artificial phospholipid spherules prepared with long-chain polar compounds. To determine whether this effect was due to the interaction of polyenes with ovolecithin alone or with highly charged components, the composition of such artificial spherules was varied. Neither variations in the sign or amount of the charged component (anionic dicetylphosphate or cationic stearylamine in 5–20% molar ratios) altered the response of spherules to polyenes in the direction expected if the antibiotics interacted preferentially with long-chain polar lipids. When increasing amounts of cholesterol were incorporated into the spherules, leakage of anions or glucose induced by nystatin or amphotericin B was proportionately increased, whereas the action of filipin was independent of the presence of cholesterol. The amount of anions captured by the spherules varied directly with the molar ratios of the charged components, being greater for negative than for positive spherules. The experiments suggest that polyene antibiotics alter the gross permeability of lipid spherules by virtue of their direct interaction with phospholipids, and not with long-chain polar compounds, and that their effects are independent of the overall charge of the target structures. Nystatin and amphotericin B appear to differ qualitatively from filipin in their mode of action by preferentially disrupting membrane systems which contain cholesterol.