Two mutants selectively resistant to polyenes reveal distinct mechanisms of antifungal activity by nystatin and amphotericin B

Polyene macrolides nystatin and amphotericin B are widely used in the treatment of fungal infections. In order to characterize factors affecting polyene activity, we have isolated Saccharomyces cerevisiae mutants showing selective resistance to nystatin and amphotericin B. Characterization of two of these mutants (nystatin-resistant mutant X1/16 and amphotericin B-resistant mutant X3/33) is presented. Genetic analysis revealed that resistance in each of these mutants is caused by a mutation in one gene with a different mode of inheritance. Nystatin resistance in mutant X1/16 is caused by changes in sterol spectrum while amphotericin B resistance in mutant X3/33 is probably related to modification of the cell wall. Our results suggest that, in spite of their structural similarity, nystatin and amphotericin B differ significantly in mechanisms of their antifungal activity.

LINKAGE ANALYSIS OF NYSTATIN RESISTANCE MUTATIONS IN DICTYOSTELIUM DISCOIDEUM

ABSTRACT Earlier linkage analyses of nystatin resistance loci in Dictyostelium discoideum tentatively mapped the nysB and nysC loci to the previously unmarked linkage group V. The data presented here establishes that nysB maps to linkage group VI and that nysC maps to linkage group IV. The third nystatin resistance locus, nysA, maps to linkage group II.

USE OF NYSTATIN-RESISTANT MUTATIONS IN PARASEXUAL GENETIC ANALYSIS IN DICTYOSTELIUM DISCOIDEUM

ABSTRACT Nystatin-resistant mutations exhibit extreme sensitivity to 1.3 mm coumarin. The mutations fall into three complementation groups so it is possible to select for nonallelic mutations conferring sensitivity to coumarin by selection on nystatin-containing nutrient agar plates. Complementation between such coumarin-sensitive mutations allows the selection of diploids on coumarin-containing nutrient agar. Two of the nystatin resistance genes, nysB and nysC, have been mapped tentatively to the previously unmarked linkage group V.