Effect of High Concentrations of Nystatin upon Glycolysis and Cellular Permeability in Yeast.

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Abstract
Nystatin (NY) inhibits growth and substrate utilization by a variety of fungi and causes leakage of inorganic ions, dicarboxylic acids, and sugar phosphates from the treated cells. The effects of varying concentration of NY on permeability characteristics of Saccharomyces cerevisiae strain LK2G12 and the relative importance of these altered characteristics were examined. At minimal inhibitory levels of NY, loss of potassium ion occurred. Inorganic phosphate and ammonium ions were lost at slightly greater concentrations. At high NY levels, log phase cells leaked sugar phosphates and nucleotides but relatively little protein. The glycolytic enzymes remained in the treated cells or protoplasts; however, glycolysis now required all the cofactors essential for a cell-free glycolytic system or protoplast lysate. The rate of CO2 production by the supplemented NY-treated cells or by osmotically-lysed protoplasts did not exceed 30% of that obtained with the original preparations. Pyruvate decarboxylase became accessible to pyruvate ion following treatment with high levels of NY. Permeability to phosphate esters appears limited, since glucose-6-phosphate and fructose-1, 6-diphos-phate were not fermented by the treated cells although catalytic quantities of DPN, thiamine phyrophosphate, and adenylic acid could be supplied exogenously. The results support the suggestion that the inhibitory actions of NY depend on damage to selective permeability mechanisms.

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