OxyR is a key regulator in response to oxidative stress in Streptomyces avermitilis

The role of the H₂O₂-sensing transcriptional regulator OxyR in oxidative stress responses in Streptomyces avermitilis was investigated. An oxyR deletion mutant was more sensitive to H₂O₂ and tert-butyl hydroperoxide than was the WT strain, indicating that OxyR mediates the defensive system against H₂O₂ and organic peroxide. Evidence presented herein suggests that in cells treated with exogenous H₂O₂, the oxidized form of OxyR activated expression of ahpCD by binding to a palindromic sequence of the promoter region. Oxidized OxyR also induced expression of other antioxidant enzymes (KatA1, KatA2, KatA3 and OhrB1) and oxidative stress regulators (CatR, OhrR and σ^R). The thiol-oxidative stress regulator gene sigR was regulated at the transcription level by OxyR. We conclude that OxyR is necessary to activate transcription of sigR from the σ^R-dependent promoter to express an unstable larger isoform of σ^R during oxidative stress. In response to oxidative stress, OxyR facilitates rapid production of H₂O₂-scavenging enzymes to repair oxidative damage through direct regulation and cascaded regulation of CatR, OhrR and σ^R.