Overproduction of peroxide-scavenging enzymes in Escherichia coli suppresses spontaneous mutagenesis and sensitivity to redox-cycling agents in oxyR-mutants.
Mutations that suppressed the H2O2 sensitivity of Escherichia coli oxyR- strains caused elevated levels of one three enzymes that destroy organic and hydrogen peroxides: catalase-hydroperoxidase I (the katG gene product), catalase-hydroperoxidase II (controlled by katEF) or alkyl hydroperoxide reductase (specified by the ahp genes). The continuous high-level expression of any one of these enzymes also conferred resistance in an oxyR deletion mutant against other compounds such as N-ethylmaleimide and the superoxide-generator menadione. Overproduction of alkyl hydroperoxide reductase, but not of the catalases, gave resistance to the organic oxidant cumene hydroperoxide. The E. coli delta oxyR strains also exhibited a strongly elevated frequency of spontaneous mutagenesis, as reported for such mutants in Salmonella typhimurium. This mutagenesis was greatly diminished by the individual overexpression of these scavenging enzymes. All of these phenotypes--enzyme overproduction, resistance to oxidants and suppression of spontaneous mutagenesis--remained linked upon transduction of the mutant katG or ahp genes. Peroxides thus appear to mediate the toxicity of a variety of redox agents, and are produced in sufficient quantity during normal metabolism to cause a substantial increase in 'spontaneous' mutations in cells that lack adequate antioxidant defenses.
Greenberg
J T
JT
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
Demple
B
B
D002374:Catalase / Q000096:biosynthesis / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D009195:Peroxidase / Q000096:biosynthesis / Q000235:genetics*; D010544:Peroxidases; D054464:Peroxiredoxins; D013489:Suppression, Genetic
D029968:Escherichia coli Proteins; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D010544:Peroxidases; D054464:Peroxiredoxins; D002374:Catalase; C051253:katG protein, E coli; D009195:Peroxidase