Oxidative Stress and Free Radical Signal Transduction

This chapter explains the oxidative stress and free radical signal transduction in the bacterias Escherichia coli and Salmonella enterica (typhimurium). The system in E. coli and S. enterica works in two stages of transcriptional control. The first stage involves direct redox signal transduction and the activated SoxR in P. aeruginosa and P. putida seems to act directly on the promoters of several genes without the need for an intermediary transcription factor. SoxR protein is activated in cells exposed to oxidative stress or nitric oxide and the activated SoxR in E. coli and S. enterica then stimulates expression of just one gene, soxS. SoxR is activated by nitric oxide that directly modifies the (2Fe-2S) clusters to form dinitrosyl-iron-dicysteine complexes anchored to the protein. These nitrosylated complexes are quite stable in vitro, which allows NO-modified SoxR to be repurified for analysis. In E. coli, SoxR activation by NO may play a role in bacterial resistance to the cytotoxic attack of NO-generating macrophages. Like SoxR, OxyR is a positive regulator that exists in a resting state in non-stressed cells. Upon cellular exposure to H2O2 or nitrosothiols, the protein is activated to stimulate transcription of the regulon genes. The positioning of the protein upstream of the RNA polymerase binding site stimulates transcription through protein–protein contacts with the C-terminal domain of the polymerase α subunit. The oxyR regulon includes antioxidant genes such as katG (HP-I catalase-hydroperoxidase), gor (GSH reductase), and the ahpFC operon (alkyl hydroperoxide reductase).