Some physiological alterations associated with pleiotropic cross resistance and collateral sensitivity in Saccharomyces cerevisiae

Summary A mutant strain (2–20) isolated by growth on medium containing oligomycin and cycloheximide was also found to be cross resistant to antimycin, cerulenin, chloramphenicol, tetracycline, triethyltin and triphenylmethylphosphonium bromide, but collaterally sensitive to dequalinium chloride, gentamycin, neomycin, paromomycin and thiolutin. Growth of 2–20, compared to the parental strain and 2 complete revertants, under a variety of environmental conditions revealed that strain 2–20 had an enhanced sensitivity to increased osmolality, elevated pH, and high temperature; in addition, strain 2–20 was unable to polymerize aminoimidazole ribotide at 37° C as shown by the failure to develop a red colony in the presence of ade 2. Four complex solid media (glucose-KCl, galactose, ethanol, ethanol-KCl, Table 1) unable to sustain the growth of strain 2–20 were arbitrarily chosen to monitor cellular growth under different physiological conditions. Tetrad analysis indicated that the complex phenotype (cross resistance, collateral sensitivity, inability to polymerize aminoimidazole ribotide, absence of growth under adverse physiological conditions) was inherited by an allele of a locus previously shown to result in a permeability barrier of the plasma membrane to chloramphenicol. 582 of 640 subclones used to isolate revertants of 2–20, under four different physiological conditions, were observed to produce a complete revertant of the complex phenotype. It is proposed that the pleiotropic phenotype could result from an alteration of the plasma membrane and mitochondrial inner membrane by a single nuclear gene mutation.