Defining the disulphide stress response in Streptomyces coelicolor A3(2): Identification of the σR regulon

Mark S.B. Paget*, Virginie Molle, Gerald Cohen, Yair Aharonowitz, Mark J. Buttner

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


In the Gram-positive, antibiotic-producing bacterium Streptomyces coelicolor A3(2), the thiol-disulphide status of the hyphae is controlled by a novel regulatory system consisting of a sigma factor, σR, and its cognate anti-sigma factor, RsrA. Oxidative stress induces intramolecular disulphide bond formation in RsrA, which causes it to lose affinity for σR, thereby releasing σR to activate transcription of the thioredoxin operon, trxBA. Here, we exploit a preliminary consensus sequence for σR target promoters to identify 27 new σR target genes and operons, thereby defining the global response to disulphide stress in this organism. Target genes related to thiol metabolism encode a second thioredoxin (TrxC), a glutaredoxin-like protein and enzymes involved in the biosynthesis of the low-molecular-weight thiol-containing compounds cysteine and molybdopterin. In addition, the level of the major actinomycete thiol buffer, mycothiol, was fourfold lower in a sigR null mutant, although no candidate mycothiol biosynthetic genes were identified among the σR targets. Three σR target genes encode ribosome-associated products (ribosomal subunit L31, ppGpp synthetase and tmRNA), suggesting that the translational machinery is modified by disulphide stress. The product of another σR target gene was found to be a novel RNA polymerase-associated protein, RbpA, suggesting that the transcriptional machinery may also be modified in response to disulphide stress. We present DNA sequence evidence that many of the targets identified in S. coelicolor are also under the control of the σR homologue in the actinomycete pathogen Mycobacterium tuberculosis.

Original languageEnglish
Pages (from-to)1007-1020
Number of pages14
JournalMolecular Microbiology
Issue number4
StatePublished - 2001


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