SigRRsrA

SigR and RsrA form a regulatory pair found in several actinobacteria, notably Streptomyces species, that controls the bacterial oxidative stress response. SigR is an extracytoplasmic function (ECF) sigma factor that redirects RNA polymerase to transcribe genes involved in redox protection, while RsrA is a zinc-binding anti-sigma factor that binds SigR and prevents its activity under non-stress conditions. The SigR/RsrA system acts as a redox-sensitive switch coordinating expression of the SigR regulon.

Under reducing, non-stress conditions, RsrA binds SigR tightly, keeping transcription of the oxidative stress genes off. When cells experience oxidative or thiol-oxidative stress, cysteine residues in RsrA form disulfide bonds, causing a conformational change that lowers RsrA’s affinity for SigR. This releases SigR, which associates with RNA polymerase to activate transcription of the SigR regulon, including genes encoding components of the thioredoxin system and other redox-protective proteins. Once redox balance is restored, reductive pathways (such as thioredoxin systems) reduce RsrA, restoring the complex and repressing SigR activity.

Genomic arrangement typically places sigR and rsrA in close proximity, often as an operon, with substantial conservation across actinobacteria though regulatory details can vary. The SigR/RsrA module is a widely cited model of bacterial redox sensing and stress adaptation, and it has implications for understanding secondary metabolism and antibiotic production in Streptomyces.