The phosphorelay BarA/SirA activates the non-cognate regulator RcsB in Salmonella enterica

Salvail, Hubert; Groisman, Eduardo A.

doi:10.1371/journal.pgen.1008722

Cited by 20 publications

(11 citation statements)

References 67 publications

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“…We recently discovered similar coordinate control of surface-based phage immunity and CRISPR–Cas by the Rcs envelope stress response phosphorelay ( 20 ). Interestingly, a recent study in Salmonella discovered that SirA (PigQ in Serratia ) activated the rcsDB operon and that BarA ( Serratia PigW) could phosphorylate the RcsB transcriptional regulator ( 83 ). We have also previously shown that pigQ transcription is quorum sensing-dependent ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

The Rsm (Csr) post-transcriptional regulatory pathway coordinately controls multiple CRISPR–Cas immune systems

Campa

Smith

Hampton

et al. 2021

Nucleic Acids Research

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CRISPR–Cas systems provide bacteria with adaptive immunity against phages and plasmids; however, pathways regulating their activity are not well defined. We recently developed a high-throughput genome-wide method (SorTn-seq) and used this to uncover CRISPR–Cas regulators. Here, we demonstrate that the widespread Rsm/Csr pathway regulates the expression of multiple CRISPR–Cas systems in Serratia (type I-E, I-F and III-A). The main pathway component, RsmA (CsrA), is an RNA-binding post-transcriptional regulator of carbon utilisation, virulence and motility. RsmA binds cas mRNAs and suppresses type I and III CRISPR–Cas interference in addition to adaptation by type I systems. Coregulation of CRISPR–Cas and flagella by the Rsm pathway allows modulation of adaptive immunity when changes in receptor availability would alter susceptibility to flagella-tropic phages. Furthermore, we show that Rsm controls CRISPR–Cas in other genera, suggesting conservation of this regulatory strategy. Finally, we identify genes encoding RsmA homologues in phages, which have the potential to manipulate the physiology of host bacteria and might provide an anti-CRISPR activity.

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Section: Discussionmentioning

confidence: 99%

The Rsm (Csr) post-transcriptional regulatory pathway coordinately controls multiple CRISPR–Cas immune systems

Campa

Smith

Hampton

et al. 2021

Nucleic Acids Research

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“…RcsB can also act in combination with other auxiliary transcriptional factors in a phosphorylation dependent or independent manner ( 3 ). In addition, the sensor protein BarA can also activate the RcsB protein in an RcsC- and RcsD-independent manner ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Structure-based analyses ofSalmonellaRcsB variants unravel new features of the Rcs regulon

Huesa

Giner‐Lamia

Pucciarelli

et al. 2021

Nucleic Acids Research

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RcsB is a transcriptional regulator that controls expression of numerous genes in enteric bacteria. RcsB accomplishes this role alone or in combination with auxiliary transcriptional factors independently or dependently of phosphorylation. To understand the mechanisms by which RcsB regulates such large number of genes, we performed structural studies as well as in vitro and in vivo functional studies with different RcsB variants. Our structural data reveal that RcsB binds promoters of target genes such as rprA and flhDC in a dimeric active conformation. In this state, the RcsB homodimer docks the DNA-binding domains into the major groove of the DNA, facilitating an initial weak read-out of the target sequence. Interestingly, comparative structural analyses also show that DNA binding may stabilize an active conformation in unphosphorylated RcsB. Furthermore, RNAseq performed in strains expressing wild-type or several RcsB variants provided new insights into the contribution of phosphorylation to gene regulation and assign a potential role of RcsB in controlling iron metabolism. Finally, we delimited the RcsB box for homodimeric active binding to DNA as the sequence TN(G/A)GAN4TC(T/C)NA. This RcsB box was found in promoter, intergenic and intragenic regions, facilitating both increased or decreased gene transcription.

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“…At first glance this data seems inconsistent. However, it may simply reflect the fact that RcsB is also subject to post-transcriptional regulation, as has been reported recently in other bacteria [37,38]. Although exploring these mechanisms is outside the scope of this study, it is possible that this post-transcriptional regulation of RcsB occurs also in Yersinia, and especially under conditions where bacteria are more sensitive to stress caused by loss of Cpx signalling.…”

Section: Cpxr Inhibits Rcsb Gene Transcriptionmentioning

confidence: 63%

CpxR regulates the Rcs phosphorelay system in controlling the Ysc-Yop type III secretion system in Yersinia pseudotuberculosis

Fei

Chao

et al. 2021

Microbiology

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The CpxRA two-component regulatory system and the Rcs phosphorelay system are both employed by the Enterobacteriaceae family to preserve bacterial envelope integrity and function when growing under stress. Although both systems regulate several overlapping physiological processes, evidence demonstrating a molecular connection between Cpx and Rcs signalling outputs is scarce. Here, we show that CpxR negatively regulates the transcription of the rcsB gene in the Rcs phosphorelay system in Yersinia pseudotuberculosis . Interestingly, transcription of rcsB is under the control of three promoters, which were all repressed by CpxR. Critically, synthetic activation of Cpx signalling through mislocalization of the NlpE lipoprotein to the inner membrane resulted in an active form of CpxR that repressed activity of rcsB promoters. On the other hand, a site-directed mutation of the phosphorylation site at residue 51 in CpxR generated an inactive non-phosphorylated variant that was unable to regulate output from these rcsB promoters. Importantly, CpxR-mediated inhibition of rcsB transcription in turn restricted activation of the Ysc-Yop type III secretion system (T3SS). Moreover, active CpxR blocks zinc-mediated activation of Rcs signalling and the subsequent activation of lcrF transcription. Our results demonstrate a novel regulatory cascade linking CpxR-RcsB-LcrF to control production of the Ysc-Yop T3SS.

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The phosphorelay BarA/SirA activates the non-cognate regulator RcsB in Salmonella enterica

Cited by 20 publications

References 67 publications

The Rsm (Csr) post-transcriptional regulatory pathway coordinately controls multiple CRISPR–Cas immune systems

The Rsm (Csr) post-transcriptional regulatory pathway coordinately controls multiple CRISPR–Cas immune systems

Structure-based analyses ofSalmonellaRcsB variants unravel new features of the Rcs regulon

CpxR regulates the Rcs phosphorelay system in controlling the Ysc-Yop type III secretion system in Yersinia pseudotuberculosis

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