Abstract
The redox-regulated transcription factor SoxR is conserved in diverse bacteria, but emerging studies suggest that this protein plays distinct physiological roles in different bacteria. SoxR regulates a global oxidative stress response (involving >100 genes) against exogenous redox-cycling drugs in Escherichia coli and related enterics. In the antibiotic producers Streptomyces coelicolor and Pseudomonas aeruginosa, however, SoxR regulates a smaller number of genes that encode membrane transporters and proteins with homology to antibiotic-tailoring enzymes. In both S. coelicolor and P. aeruginosa, SoxR-regulated genes are expressed in stationary phase during the production of endogenously-produced redox-active antibiotics. These observations suggest that SoxR evolved to sense endogenous secondary metabolites and activate machinery to process and transport them in antibiotic-producing bacteria. Previous bioinformatics analysis that searched the genome for SoxR-binding sites in putative promoters defined a five-gene SoxR regulon in S. coelicolor including an ABC transporter, two oxidoreductases, a monooxygenase and an epimerase/dehydratase. Since this in silico screen may have missed potential SoxR-targets, we conducted a whole genome transcriptome comparison of wild type S. coelicolor and a soxR-deficient mutant in stationary phase using RNA-Seq. Our analysis revealed a sixth SoxR-regulated gene in S. coelicolor that encodes a putative quinone oxidoreductase. Knowledge of the full complement of genes regulated by SoxR will facilitate studies to elucidate the function of this regulatory molecule in antibiotic producers.
Highlights
The redox-regulated transcription factor SoxR is present in a diverse range of Proteobacteria and Actinobacteria and homologs are highly similar at the amino acid level [1]
In order to identify other potential SoxR-regulated genes that might have been missed by this bioinformatic approach, we conducted RNA-Seq analysis to detect genes differentially expressed between wild type and a DsoxR mutant strain
In this work we expanded the SoxR regulon in S. coelicolor by comparing the transcriptomes of wild type and soxR null mutant strains in stationary phase using RNA-Seq. This regulon is composed of six genes induced by SoxR in response to the redoxactive antibiotic Act that is produced in stationary phase
Summary
The redox-regulated transcription factor SoxR is present in a diverse range of Proteobacteria and Actinobacteria and homologs are highly similar at the amino acid level [1]. SoxR homologs function as homodimers and have a conserved amino-terminal helix-turn-helix DNA binding domain, suggesting that these proteins bind to and regulate transcription from similar operator sequences. This has been confirmed in organisms where SoxR has been biochemically characterized [2,3,4,5,6,7]. SoxR homologs share a conserved sequence (CysX2CysXCysX5Cys) in the carboxy-terminus that has been shown to be necessary for coordinating [2Fe-2S] centers in SoxR proteins from Escherichia coli, Pseudomonas aeruginosa, and Streptomyces coelicolor [5,8,9] These [2Fe-2S] clusters are central to SoxR’s ability to detect changes in the cellular redox environment and regulate gene expression in response. SoxS, an AraC-type regulator recruits RNA polymerase to the promoters of .100 genes (the SoxRS regulon), whose protein products cumulatively restore redox homeostasis and repair oxidant-induced cellular damage [14]
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