Significance of Nystatin Uptake for Its Antifungal Action

Abstract

Summary

1) Time sequence for inhibition of yeast respiration and glycolysis by nystatin is described and its significance is discussed. 2) A series of nystatin-resistant : sensitive pairs of Candida strains was examined. With various pairs, resistance of growth to nystatin was accompanied by similar resistance of metabolic activity to the agent. Resistant strains absorbed less nystatin than did sensitive organisms under same conditions, but there was no quantitative correlation between sensitivity and absorption. Reduced uptake of nystatin is probably only one of the ways by which resistance can be achieved. 3) Addition of serum albumin, zymosan, uranyl ions, arsenate, or dinitrophenol could protect yeast metabolism in varying degrees against the action of nystatin. Inhibition, once obtained, could not be reversed. The protective action of various agents approximated that expected from their effect on absorption of nystatin by yeast. 4) The methyl ester and N-acetyl derivatives of nystatin, which do not inhibit growth or metabolism of fungi, were not absorbed to a significant extent by either fresh yeast or zymosan. Since absorption occurs primarily below pH 5, the ionic species HOOC… NH₃ ⁺ is probably the material absorbed by yeast. 5) The results furnish additional evidence for the critical nature of uptake of nystatin by microorganisms in determining sensitivity to its action.