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Action of the Polyene Antibiotics Filipin, Nystatin and n-Acetylcandidin on the Yeast Cell Membrane
Abstract
Summary: The effects of the antifungal polyene antibiotics n-acetylcandidin, nystatin and filipin on the yeast cell membranes were compared with the reversibility by K+ and NH4 + of the inhibition of glycolysis caused by these antibiotics. The results confirm the existence of two functional classes of polyenes which correspond to the number of carbon atoms in the molecule; intermediate types of action can be illustrated within the group of large polyenes. The inhibition of yeast glycolysis by n-acetylcandidin, a large polyene, was annulled by K+ and NH4 +, even at high antibiotic concentrations; inhibition by filipin, a small polyene, was not so annulled. The inhibition of glycolysis by polyenes was associated with the loss of cell K+; filipin caused concurrent loss of inorganic phosphate and of accumulated sugar (l-sorbose) and initiated ATPase and pyruvate decarboxylase activity. Although n-acetylcandidin treatment did not produce loss of accumulated sorbose, added sorbose leaked into treated cells when uptake by way of the hexose transport system had been blocked (by glucose). Thus, definite membrane damage had occurred. Nystatin, a large polyene, was intermediate in effect: at low concentrations its action approached that of n-acetylcandidin; at high concentrations, its action was similar to that of filipin. It is suggested that the polyenes present a full spectrum of effects which relate to the degree of physical damage to the cell membrane. They range from filipin which destroys general structural integrity of the membrane even at the minimum concentration necessary to inhibit glycolysis (and growth) to n-acetylcandidin which produces only minimal damage so that relatively specific defects are observed, e.g. those related to K+ loss and sorbose leakage.
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© Society for General Microbiology, 1964