OxyR

OxyR is a transcriptional regulator of the oxidative stress response in many bacteria, most notably Escherichia coli. It acts as a sensor of hydrogen peroxide and, in its oxidized form, activates a set of genes that detoxify reactive oxygen species. The regulon includes catalase-peroxidase KatG, alkyl hydroperoxide reductase AhpCF, and protective factors such as grxA and the Dps DNA-binding protein. OxyR helps bacteria survive oxidative stress encountered during aerobic growth and immune responses.

Mechanistically, OxyR contains a redox-sensitive regulatory domain with conserved cysteine residues. Upon exposure to H2O2, these cysteines form a disulfide bond, triggering a conformational change that alters DNA-binding affinity and specificity. In the oxidized state, OxyR acts as an activator for many target promoters, upregulating antioxidant genes; in some contexts it can repress others. Reduction by thioredoxin or glutaredoxin systems returns OxyR to the reduced state, resetting transcription.

Structurally, OxyR functions as a transcription factor with a DNA-binding domain and a redox-sensing regulatory domain. In many bacteria it forms a regulatory dimer or higher-order oligomer that binds promoter regions to control transcription in response to redox changes. The OxyR regulon is widely conserved among Gram-negative bacteria and is sometimes integrated with other stress response systems, such as SoxR/SoxS.

Although primarily studied in E. coli, OxyR homologs exist in diverse species and contribute to resistance to peroxide stress and, in some pathogens, to virulence and survival within hosts. Its activity provides a rapid, reversible mechanism for adjusting gene expression to oxidative conditions.