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

journal contribution
posted on 2023-06-08, 08:50 authored by Mark PagetMark Paget, Virginie Molle, Gerald Cohen, Yair Aharonowitz, Mark J Buttner
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, sR, and its cognate anti-sigma factor, RsrA. Oxidative stress induces intramolecular disulphide bond formation in RsrA, which causes it to lose affinity for sR, thereby releasing sR to activate transcription of the thioredoxin operon, trxBA. Here, we exploit a preliminary consensus sequence for sR target promoters to identify 27 new sR 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 sR targets. Three sR 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 sR 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 sR homologue in the actinomycete pathogen Mycobacterium tuberculosis.

History

Publication status

  • Published

Journal

Molecular Microbiology

ISSN

0950-382X

Issue

4

Volume

42

Page range

1007-1020

Pages

14.0

Department affiliated with

  • Biochemistry Publications

Notes

Paget was a post-doctoral fellow and recognised researcher on the BBSRC grant that funded the project. Paget played the major role in experimental design, data collection, and interpretation, and is corresponding author. The paper was written by Paget in the early stages of his lectureship at Sussex.

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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