Defining the disulphide stress response in Streptomyces coelicolor A3(2): identification of the sigma(R) regulon

In the Gram-positive, antibiotic-producing bacterium Streptomyces coelicolo r A3(2), the thiol-disulphide status of the hyphae is controlled by a novel regulatory system consisting of a sigma factor, sigma (R), and its cognate anti-sigma factor, RsrA. Oxidative stress induces intramolecular disulphid e bond formation in RsrA, which causes it to lose affinity for CT thereby r eleasing sigma (R) to activate transcription of the thioredoxin operon, trx BA. Here, we exploit a preliminary consensus sequence for sigma (R) target promoters to identify 27 new sigma (R) target genes and operons, thereby de fining the global response to disulphide stress in this organism. Target ge nes related to thiol metabolism encode a second thioredoxin (TrxC), a gluta redoxin-like protein and enzymes involved in the biosynthesis of the low-mo lecular-weight thiol-containing compounds cysteine and molybdopterin. In ad dition, the level of the major actinomycete thiol buffer, mycothiol, was fo urfold lower in a sigR null mutant, although no candidate mycothiol biosynt hetic genes were identified among the sigma (R) targets. Three sigma (R) ta rget genes encode ribosome-associated products (ribosomal subunit L31, ppGp p synthetase and tmRNA), suggesting that the translational machinery is mod ified by disulphide stress. The product of another (TR target gene was foun d to be a novel RNA polymerase-associated protein, RbpA, suggesting that th e transcriptional machinery may also be modified in response to disulphide stress. We present DNA sequence evidence that many of the targets identifie d in S. coelicolor are also under the control of the sigma (R) homologue in the actinomycete pathogen Mycobacterium tuberculosis.