The bacterial response to oxidative stress: regulation by a redox sensitive transcription factor and a regulatory RNA

The bacterial responses to hydrogen peroxide and Superoxide have been models for studying how cells sense and defend againsl oxidative stress. In E. coli and S. typhimurium, the expression of at least nine hydrogen peroxide-inducible proteins, including hydroperoxidase I (katG), an alkyl hydroperoxide reductase (ahpCF), glutathione reductase (gorA), and a non-specific DNA binding protein (dps), is controlled by the LysR-type regulatoi OxyR. In vitro transcription experiments with purified components showed that the oxidized but not the reduced form of the OxyR protein activates transcription of the katG and ahpC genes, suggesting that oxidation of OxyR brings about a conformational change that leads to RNA polymerase activation DNA binding studies showed that oxidized and reduced OxyR have different binding specificities, and mutational analysis of the OxyR protein have indicated that a single cysteine residue is critica' for oxidation. We are now examining the nature of the chemical reaction leading to OxyR activation. OxyR also controls the expression of OxyS, a 109 nucleotide, non-translated RNA Overexpression of OxyS has a dramatic effect on the protein expression pattern indicating that OxyS acts to modulate gene expression. The proportion of OxyS-regulated genes in E. coli is estimated to be 1%, and several OxyS targets have been identified The mechanism of this unique regulation by an RNA is being investigated. In summary, the response to hydrogen peroxide in bacteria involves at least two distinct regulatory mechanisms. OxyR, a protein that activates transcription upon oxidation, and OxyS, non-translated RNA induced by hydrogen peroxide that acts as both an activator and a repressor of gene expression.