Conservation of thiol‐oxidative stress responses regulated by SigR orthologues in actinomycetes

Abstract

Summary Numerous thiol-reactive compounds cause oxidative stress where cells counteract by activation of survival strategies regulated by thiol-based sensors. In Streptomyces coelicolor, a model actinomycete, a sigma/antisigma pair SigR/RsrA controls the response to thiol-oxidative stress. To unravel its full physiological functions, chromatin immuno-precipitation combined with sequence and transcript analyses were employed to identify 108 SigR target genes in S. coelicolor and to predict orthologous regulons across actinomycetes. In addition to reported genes for thiol homeostasis, protein degradation and ribosome modulation, 64 additional operons were identified suggesting new functions of this global regulator. We demonstrate that SigR maintains the level and activity of the housekeeping sigma factor HrdB during thiol-oxidative stress, a novel strategy for stress responses. We also found that SigR defends cells against UV and thiol-reactive damages, in which repair UvrA takes a part. Using a refined SigR-binding sequence model, SigR orthologues and their targets were predicted in 42 actinomycetes. This revealed a conserved core set of SigR targets to function for thiol homeostasis, protein quality control, possible modulation of transcription and translation, flavin-mediated redox reactions, and Fe-S delivery. The composition of the SigR regulon reveals a robust conserved physiological mechanism to deal with thiol-oxidative stress from bacteria to human.

Expanding the Regulatory Network Governed by the Extracytoplasmic Function Sigma Factor σHin Corynebacterium glutamicum

“…In this context, it should be noted that the suf operon encoding proteins involved in Fe-S cluster biosynthesis is also included in the H regulon (14). Induction of genes for biosynthesis of stresssensitive cofactors, including the Fe-S cluster, lipoic acid, coenzyme A (CoA), and NAD, and of those for enzymes carrying the cofactors by alternative sigma factors have been known (30,56).…”

“…These findings provide new insights into the functions of H in the stress response and in the structure of the transcriptional regulatory network in C. glutamicum. Moreover, the C. glutamicum H regulon defined here has some components in common with the S. coelicolor R regulon, which has been recently identified by ChIP-chip analysis (30), indicating functional conservation of the H orthologs among Actinomycetales.…”

OxyR is a key regulator in response to oxidative stress in Streptomyces avermitilis

“…s R orthologues and their predicted regulons are well conserved in actinomycetes (Kim et al, 2012). In S. coelicolor, the activity of s R is regulated by anti-s factor RsrA, which is inactivated by formation of disulphide bonds and releases s R to transcribe its regulon under oxidative stress (Bae et al, 2004;Kang et al, 1999;Paget et al, 2001a, b).…”

“…The sigR gene in S. avermitilis also has a standard s R -dependent promoter (GGAAT-N 18 -GTT; p2) (Kim et al, 2012). Our 59-RACE analysis of sigR transcripts revealed that another promoter (p1), located 163 nt downstream of p2, was the constitutive promoter in the absence of stress (Fig.…”

“…The activity of s R is regulated by its peroxide-sensitive anti-s factor RsrA (Kang et al, 1999). Over 100 s R target genes have been identified in S. coelicolor, including those related to maintenance of thiol redox homeostasis and sulphur-containing amino acids (trxBA, trxC, mrxA, mrxB, mca, mshA, cysM, msrA and msrB), transcriptional regulators (hrdB, sigR, rsrA, sigR2 and rsrA2), proteolytic components of protein quality control ( pepN, ssrA, clpP1P2, clpX, clpC and lon) and ribosome-associated components (rpmE and relA) (Kim et al, 2012;Paget et al, 2001b). The transcriptional activator OxyR mediates H 2 O 2 induction of its own gene and of genes involved in the alkyl hydroperoxide reductase system (AhpCD) (Hahn et al, 2002).…”