Yeast mutants sensitive to trimethoprim.

Wild-type strains of Saccharomyces cerevisiae are resistant to growth inhibition by the folate antagonist trimethoprim. A mutant strain sensitive to trimethoprim was isolated. It was found to be sensitive to both ultraviolet light and X-irradiation. Genetic tests revealed that it was allelic with a known radiation-sensitive strain of Saccharomyces cerevisiae, rad 6-I. Strains harbouring a variety of mutant alleles conferring radiation-sensitivity were tested for sensitivity to trimethoprim. It was found that rad 6-I and each of the four known alleles of rad 18 conferred sensitivity to the drug, but all other rad mutants tested were trimethoprim-resistant. All trimethoprim-sensitive strains, including double mutants of rad 6 rad 18, gave rise to trimethoprim-resistant outgrowths at a rather high frequency (similar to 10-minus 5). Several resistant outgrowths were analysed. A wide variation in phenotype with respect of UV-sensitivty was found. Genetical analysis revealed that resistance to trimethoprim resulted from forward mutations at separate loci rather than back mutations of rad 6 or rad 18 alleles.