ABSORPTION OF NYSTATIN BY MICROORGANISMS

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Abstract
Nystatin, a polyene antifungal produced by Streptomyces noursei, is highly active in inhibiting the growth of a wide variety of fungi, but has little effect on other organisms or on animal cells. Nystatin was removed from aqueous solution by yeast and other fungi whose growth was inhibited by the antibiotic. This was not observed with a group of insensitive organisms. Uptake was measured by incubating cells in the presence of nystatin and determining the disappearance of the compound from the medium by decrease of absorbance at 321 m[mu]. There was no absorbance by intact cells at 0-4[degree]C. At pH 4 and below, nystatin was absorbed more rapidly and in a greater final amount than at pH 6 and above. Uptake by boiled cells was extremely rapid and showed less dependence on temperature and pH than is characteristic of intact cells. Absorbed nystatin could not be removed by washing the cells with buffer or with acetone or by changing the pH of the suspending medium. The major portion could be recovered, apparently unaltered, by extraction with 1:1 aqueous isopropanol. In the absence of a substrate which could be metabolized, absorption of nystatin by yeast cells did not occur at 30[degree]C. It is postulated that the uptake involves an initial penetration of or attachment to the cell, this phase requiring energy and depending on pH, and a subsequent binding by cell constituents which can only be reversed with difficulty. Fungi-cidal action was prevented at 0[degree]C and increased at acid pH. However, the amount of nystatin which can be absorbed is considerably in excess of that required to kill the cells.