Sensing and responding to oxidative stress in Streptomyces

We have discovered a novel redox-sensitive switche that senses and responds to unwanted disulphide bond formation (disulphide stress) in the cytoplasm of Streptomyces (Paget et al., 1998; Kang et al., 1999). The switch consists of two proteins, SigR and RsrA. SigR is a sigma factor, the subunit of bacterial RNA polymerase which confers promoter specificity on the holoenzyme, and RsrA is an anti-sigma factor, which can hold SigR inactive by binding to it. Although the SigR protein is present in the hyphae all the time, its activity is inhibited by the anti-sigma factor activity of RsrA. In vitro experiments suggest that oxidative stress induces the formation of one or more intramolecular disulphide bonds in RsrA which causes it to lose affinity for SigR, thereby allowing SigR to bind core RNA polymerase and induce transcription. SigR targets include the trxBA operon, encoding thioredoxin and thioredoxin reductase, as well as many other genes, most with no known function (unpublished data).

We have set up a multidiciplinary collaboration involving Prof Jung-Hye Roe (Seoul National University), Dr Mark Buttner and Dr David Lawson (John Innes Centre), and Prof Colin Kleanthous and Prof Geoff Moore (University of East Anglia), with the aim of (1) uncovering the redox sensing mechanism of this system (2) understanding the SigR-RsrA interaction, and (3) investigating the global response to disulphide stress.