Streptomyces coelicolor Encodes a Urate-Responsive Transcriptional Regulator with Homology to PecS from Plant Pathogens

Abstract

Many transcriptional regulators control gene activity by responding to specific ligands. Members of the multiple-antibiotic resistance regulator (MarR) family of transcriptional regulators feature prominently in this regard, and they frequently function as repressors in the absence of their cognate ligands. Plant pathogens such as Dickeya dadantii encode a MarR homolog named PecS that controls expression of a gene encoding the efflux pump PecM in addition to other virulence genes. We report here that the soil bacterium Streptomyces coelicolor also encodes a PecS homolog (SCO2647) that regulates a pecM gene (SCO2646). S. coelicolor PecS, which exists as a homodimer, binds the intergenic region between pecS and pecM genes with high affinity. Several potential PecS binding sites were found in this intergenic region. The binding of PecS to its target DNA can be efficiently attenuated by the ligand urate, which also quenches the intrinsic fluorescence of PecS, indicating a direct interaction between urate and PecS. In vivo measurement of gene expression showed that activity of pecS and pecM genes is significantly elevated after exposure of S. coelicolor cultures to urate. These results indicate that S. coelicolor PecS responds to the ligand urate by attenuated DNA binding in vitro and upregulation of gene activity in vivo. Since production of urate is associated with generation of reactive oxygen species by xanthine dehydrogenase, we propose that PecS functions under conditions of oxidative stress.

PecS regulates the urate-responsive expression of type 1 fimbriae in Klebsiella pneumoniae CG43

“…NT, nickel transporter; CL, citrate lyase; HP, hypothetical protein. Huang et al, 2013b). In addition, a putative CpxR binding sequence, GTAAA-(N) 4-8 -GTAAA (Yamamoto & Ishihama, 2006), could be identified.…”

“…6e). Analysis of the 59 upstream non-coding sequence of hns reveals three putative palindromic-like sequences (CTTNNNNNNAAG) predicted as the binding site for D. dadantii PecS (Huang, et al, 2013b). We propose that, in the presence of excess urates and the absence of CpxAR, PecS is no longer able to bind the promoter sequence of hns, which in turn reduces the expression of HNS and consequently the repression of HNS on the expression of type 1 fimbriae is released.…”

“…The plant pathogens may use urate as a signal to release the PecS-mediated suppression, which in turn increases virulent gene expression for effective colonization (Hommais et al, 2008;Perera & Grove, 2010;Mhedbi-Hajri et al, 2011). However, S. coelicolor PecS is proposed as the oxidative stress response activator as urate production is associated with the generation of reactive oxygen species (Huang et al, 2013b).…”

“…In addition, the binding activity of PecS to pecO could be attenuated by exogenous urate in A. tumefaciens and S. coelicolor (Perera & Grove, 2010Huang et al, 2013b). Urates are secreted for the prevention of extended tissue damage when a plant is invaded by phytopathogens (Alamillo & García-Olmedo, 2001;Averyanov, 2009).…”

A MarR Family Transcriptional Regulator, DptR3, Activates Daptomycin Biosynthesis and Morphological Differentiation in Streptomyces roseosporus

“…S. coelicolor TamR controls the expression of the gene encoding trans-aconitate methyltransferase (tam) and is important for metabolic flux through the citric acid cycle during oxidative stress (18). S. coelicolor PecS was proposed to function under oxidative stress conditions by responding to the ligand urate (19). S. coelicolor PcaV controls the transcription of genes encoding ␤-ketoadipate pathway enzymes (which are essential for aromatic catabolism) through its interaction with the pathway substrate protocatechuate (PCA) (20).…”