RsrA an anti-sigma factor regulated by redox change

SigR (s(R)) is a sigma factor responsible for inducing the thioredoxin system in response to oxidative stress in the antibiotic-producing, Gram-positive bacterium Streptomyces coelicolor A3(2). Here we identify a redox-sensitive, s(R)-specific anti-sigma factor, RsrA, which binds s(R) and inhibits s(R)-directed transcription in vitro only under reducing conditions. Exposure to H2O2 or to the thiol-specific oxidant diamide caused the dissociation of the s(R)-RsrA complex, thereby allowing s(R)-dependent transcription. This correlated with intramolecular disulfide bond formation in RsrA. Thioredoxin was able to reduce oxidized RsrA, suggesting that s(R), RsrA and the thioredoxin system comprise a novel feedback homeostasis loop that senses and responds to changes in the intracellular thiol-disulfide redox balance.