Significance of Nystatin Uptake for Its Antifungal Action

Abstract
The time sequence was determined for the inhibition of metabolism of commercial bakers'' yeast by nystatin. Following nystatin addition, the rate of CO2 production (or O2 uptake) in bakers'' yeast was normal or elevated until a sudden cessation of activity occurred. It has not been possible to reverse this process. The primary effect of nystatin concentration was to determine the time required before the sharp drop in activity took place. Sensitive Candida strains absorbed more nystatin than did resistant ones but a quantitative relationship between sensitivity and absorption was not obtained. Reduction of nystatin absorption is probably only one of the ways by which resistance can be achieved. The protective action of various agents against nystatin inhibition of yeast metabolism was studied. Varying degrees of such protection were observed with serum albumin, zymosan, uranyl ions, arsenate and dinitrophenol. Inhibition, once obtained, could not be reversed. There was a correlation between the protective action and the decrease in absorption of nystatin effected by the agents studied. The methyl ester and N-acetyl derivativies of nystatin, which exerted a minimal effect on the growth or metabolism of yeast, were poorly absorbed by the cells. Since absorption occurs maximally below pH 5.0, the ionic species HOOC... NH3 + is probably the material absorbed by yeast.