Copper/zinc-superoxide dismutase is required for oxytetracycline resistance of Saccharomyces cerevisiae

Saccharomyces cerevisiae, along with other eukaryotes, is resistant to tetracyclines. We found that deletion of SOD1 (encoding Cu/Zn superoxide dismutase) rendered S. cerevisiae hypersensitive to oxytetracycline (OTC): a sod1 Delta mutant exhibited a >95% reduction in colony-forming ability at an OTC concentration of 20 mu g ml(-1), whereas concentrations of up to 1,000 mu g ml(-1) had no effect on the growth of the wild type. OTC resistance was restored in the sod1 Delta mutant by complementation with wild type SOD1, The effect of OTC appeared to be cytotoxic and was not evident in a ctt1 Delta (cytosolic catalase) mutant or in the presence of tetracycline, SOD1 transcription was not induced by OTC, suggesting that constitutive SOD1 expression is sufficient for wild-type OTC resistance. OTC uptake levels in wild-type and sod1 Delta strains were similar. However, lipid peroxidation and protein oxidation were both enhanced during exposure of the sod1 Delta mutant, but not the wild type, to OTC, We propose that Sod1p protects S. cerevisiae against a mode of OTC action that is dependent on oxidative damage.