Modification and inheritance of pleiotropic cross resistance and collateral sensitivity in Saccharomyces cerevisiae.
A meiotic segregant (oliPR1) was isolated with a phenotype of multiple cross resistance and collateral sensitivity. Strain oliPR1 has increased sensitivity to ethidium bromide, dequalinium chloride, acriflavin, paromomycin and neomycin, and increased resistance to oligomycin, rutamycin, venturicidin, triethyltin bromide, antimycin, carbonylcynamide-m-chlorophenylhydrazone, tetra-N-butylammonium bromide, dibenzyldimethylammonium chloride, triphenylmethlphosphonium bromide, chloramphenicol, carbomycin, tetracycline, triton X-165 and cycloheximide. Single gene inheritance of the cross resistance and collateral sensitivity was shown by 2:2 parental ditype segregation and reversion of the complete phenotype by a spontaneous revertant. The locus conferring the oliPR1 phenotype was mapped 11.7 units from an unspecified centromere. Antibiotic resistance showed incomplete dominance, with the level of hybrid resistance dependent upon the inhibitor tested. Resistant diploids that produced four resistant ascospores were the result of mitotic recombination prior to meiosis. A partial revertant phenotype (sensitive to all inhibitors except oligomycin, antimycin and carbonylcyanide-m-chlorophenylhydrazone) was shown to be due to a single nuclear gene causing partial suppression of oliPR1. Anaerobic pretreatment, 37degrees and 0.5 MKC1 were observed to reduce the growth of oliPR1 when challenged with seven diverse inhibitors (antimycin, carbonylcyanide-m-chlorophenylhydrazone,-chloramphenicol, cycloheximide, oligomycin, triethyltin bromide, and triphenylmethylphosphonium bromide). Resistance to cycloheximide was not altered by the [rho--] state. A revertant of oliPR1 (sensitive to the above inhibitors but resistant to ethidium bromide, paromycin and neomycin) showed anaerobic and temperature sensitization to ethidium bromide, paromomycin and neomycin. Continuous monitoring of oxygen uptake by the revertant afteranaerobic pretreatment revealed that anaerbiosis sensitized respiratory adaptation of the revertant to neomycin. It is proposed that oliPR1 is a mutation resulting in the alteration of plasma membrane permeability to many diverse inhibitors.
D000968:Antimycin A / Q000494:pharmacology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002701:Chloramphenicol / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004917:Erythromycin / Q000494:pharmacology; D004996:Ethidium / Q000494:pharmacology; D005796:Genes; D009154:Mutation; D009355:Neomycin / Q000494:pharmacology; D009840:Oligomycins / Q000494:pharmacology; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000187:drug effects*; D013730:Terphenyl Compounds / Q000494:pharmacology; D013752:Tetracycline / Q000494:pharmacology; D014267:Triethyltin Compounds / Q000494:pharmacology
D009840:Oligomycins; D013730:Terphenyl Compounds; D014267:Triethyltin Compounds; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D004917:Erythromycin; D000968:Antimycin A; D002701:Chloramphenicol; D003513:Cycloheximide; D004996:Ethidium; D013752:Tetracycline; D009355:Neomycin