Spontaneous and induced non-specific drug resistance in Saccharomyces cerevisiae

Nitrous acid, diepoxybutane and methyl methane sulfonate induce effectively non-mitochondrial chloramphenicol-resistant mutants cross-resistant to other drugs. HNO2 induces also unstable erythromycin resistant mutants. The ability of the mutants to grow on antibiotic media can be modified by detergents, guanidine hydrochloride or increased osmotic pressure of the medium. This suggests that the resistance is due to changes in cell membrane permeability similar to those described by Rank, Robertson and Philips (1975b). Multiple drug-resistant mutants selected for chloramphenicol resistance show an increased sensitivity to ethidium bromide in glucose medium. Therefore the mutations involved increase probably nuclear envelope permeability to the latter drug. Results of genetic analyses of non-mitochondrial capr and eryr mutants suggest strongly that in most, if not all, cases the resistance is determined by interaction between nuclear and extranuclear factors.