RsrA, an anti-sigma factor regulated by redox change

SigR (sigma(R)) is a sigma factor responsible for inducing the thioredoxin system in response to oxidative stress in the antibiotic-producing, Gram-po sitive bacterium Streptomyces coelicolor A3(2), Here we identify a redox-se nsitive, sigma(R)-specific anti-sigma factor, RsrA, which binds sigma(R) an d inhibits sigma(R)- directed transcription in vitro only under reducing co nditions. Exposure to H2O2 or to the thiol-specific oxidant diamide caused the dissociation of the sigma(R)-RsrA complex, thereby allowing sigma(R)-de pendent transcription. This correlated with intramolecular disulfide bond f ormation in RsrA, Thio redoxin was able to reduce oxidized RsrA, suggesting that sigma(R), RsrA and the thioredoxin system comprise a novel feedback h omeostasis loop that senses and responds to changes in the intracellular th iol-disulfide redox balance.