CsrA and three redundant small RNAs regulate quorum sensing in <i>Vibrio cholerae</i>

Lenz, Derrick H.; Miller, Melissa B.; Zhu, Jun; Kulkarni, Rahul; Bassler, Bonnie L.

doi:10.1111/j.1365-2958.2005.04902.x

Cited by 297 publications

(395 citation statements)

References 48 publications

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“…The Csr system appears to be conserved in all Gammaproteobacteria species, but details such as the number of CsrA paralogs and Csr sRNAs produced by a given species can differ (6,44,75,76). Not surprisingly, even among closely related Enterobacteriaceae species, the links between Csr and catabolite repression circuitry differ.…”

Section: Discussionmentioning

confidence: 99%

Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli

et al. 2016

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Cyclic AMP (cAMP) and the cAMP receptor protein (cAMP-CRP) and CsrA are the principal regulators of the catabolite repression and carbon storage global regulatory systems, respectively. cAMP-CRP controls the transcription of genes for carbohydrate metabolism and other processes in response to carbon nutritional status, while CsrA binds to diverse mRNAs and regulates translation, RNA stability, and/or transcription elongation. CsrA also binds to the regulatory small RNAs (sRNAs) CsrB and CsrC, which antagonize its activity. The BarA-UvrY two-component signal transduction system (TCS) directly activates csrB and csrC (csrB/C) transcription, while CsrA does so indirectly. We show that cAMP-CRP inhibits csrB/C transcription without negatively regulating phosphorylated UvrY (P-UvrY) or CsrA levels. A crp deletion caused an elevation in CsrB/C levels in the stationary phase of growth and increased the expression of csrB-lacZ and csrClacZ transcriptional fusions, although modest stimulation of CsrB/C turnover by the crp deletion partially masked the former effects. DNase I footprinting and other studies demonstrated that cAMP-CRP bound specifically to three sites located upstream from the csrC promoter, two of which overlapped the P-UvrY binding site. These two proteins competed for binding at the overlapping sites. In vitro transcription-translation experiments confirmed direct repression of csrC-lacZ expression by cAMP-CRP. In contrast, cAMP-CRP effects on csrB transcription may be mediated indirectly, as it bound nonspecifically to csrB DNA. In the reciprocal direction, CsrA bound to crp mRNA with high affinity and specificity and yet exhibited only modest, conditional effects on expression. Our findings are incorporated into an emerging model for the response of Csr circuitry to carbon nutritional status. IMPORTANCECsr (Rsm) noncoding small RNAs (sRNAs) CsrB and CsrC of Escherichia coli use molecular mimicry to sequester the RNA binding protein CsrA (RsmA) away from lower-affinity mRNA targets, thus eliciting major shifts in the bacterial lifestyle. CsrB/C transcription and turnover are activated by carbon metabolism products (e.g., formate and acetate) and by a preferred carbon source (glucose), respectively. We show that cAMP-CRP, a mediator of classical catabolite repression, inhibits csrC transcription by binding to the upstream region of this gene and also inhibits csrB transcription, apparently indirectly. We propose that glucose availability activates pathways for both synthesis and turnover of CsrB/C, thus shaping the dynamics of global signaling in response to the nutritional environment by poising CsrB/C sRNA levels for rapid response.T he Csr (carbon storage regulator) or Rsm (repressor of stationary-phase metabolites) system is a widely conserved bacterial posttranscriptional regulatory system (1-3). Its components, their functions, and the mechanisms by which the central regulator of this system, CsrA or RsmA, affects gene expression have been studied primarily in Gammaproteobacteria (4-6). The...

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Section: Discussionmentioning

confidence: 99%

Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli

et al. 2016

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“…reporter required growth at 30 uC. In-frame deletion mutants of luxO, hapR and varA were constructed as previously described (Lenz et al, 2005;Zhu et al, 2002). The in-frame deletion mutant for pckA and vc0191 was constructed by using pWM91 (Metcalf et al, 1996).…”

Section: Methodsmentioning

confidence: 99%

“…The signals that activate VarS/VarA-type systems have not yet been definitively established. VarS and VarA activate the transcription of csrB, csrC and csrD, which encode untranslated small RNAs that bind to and inhibit the activity of CsrA (Lenz et al, 2005;Liu et al, 1997;Weilbacher et al, 2003). CsrA is a post-transcriptional regulator that can act as both an activator and a repressor.…”

Section: Introductionmentioning

confidence: 99%

The VarS/VarA two-component system modulates the activity of the Vibrio cholerae quorum-sensing transcriptional regulator HapR

Tsou

Cai

et al. 2011

Microbiology

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The human pathogen Vibrio cholerae uses quorum sensing to regulate the expression of a number of phenotypes, including virulence factor production, in response to changes in cell density. It produces small molecules called autoinducers that increase in concentration as cell density increases, and these autoinducers bind to membrane sensors once they reach a certain threshold. This binding leads to signalling through a downstream phosphorelay pathway to alter the expression of the transcriptional regulator HapR. Previously, it was shown that the VarS/VarA two-component system acts on a component of the phosphorelay pathway upstream of HapR to regulate HapR expression levels. Here, we show that in addition to this mechanism of regulation, VarS and VarA also indirectly modulate HapR protein activity. This modulation is mediated by the small RNA CsrB but is independent of the known quorum-sensing system that links the autoinducers to HapR. Thus, the VarS/VarA two-component system intersects with the quorumsensing network at two levels. In both cases, the effect of VarS and VarA on quorum sensing is dependent on the Csr small RNAs, which regulate carbon metabolism, suggesting that V. cholerae may integrate nutrient status and cell density sensory inputs to tailor its gene expression profile more precisely to surrounding conditions.

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“…System I is the Cholera Autoinducer-1 (CAI-1)/CqsS system responsible for inter-vibrio and intra-species communication [2,30,31] System II-Autoinducer-2 (AI-2)/LuxP/Q responsible for inter species communication [2,30,31] and the System III -Unknown signals/VarS which is yet to be explored [32]. At LCD, both the enzymes CqsA and LuxS that synthesize CAI-1 & AI-2 [30,33] produce them in a lower concentration.…”

Section: Quorum Sensing In Vibrio Choleraementioning

confidence: 99%

“…LuxO is the point of convergence of both the system I and II [2,31,34,35]. System III converges with System I and System II at LuxO protein through activation of VarS/A pathway but the exact mechanism of the series of steps that occur to activate LuxO is unknown [2,32]. Phosphorylated LuxO along with r 54 is in turn, a transcriptional activator of the Quorum regulatory RNAs (Qrr1-4).…”

Section: Quorum Sensing In Vibrio Choleraementioning

confidence: 99%

Meddling Vibrio cholerae Murmurs: A Neoteric Advancement in Cholera Research

2015

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Cholera, a known diarrheal disease is associated with various risk factors like hypovolemic shock, rice watery stools, and death in developing countries. The overuse of antibiotics to treat cholera imposed a selective pressure for the emergence and spread of multi-drug resistant Vibrio cholerae strains. The failure of conventional antimicrobial therapy urged the researchers to find an alternative therapy that could meddle the cholera murmurs (Quorum Sensing). It seems to effectively overcome the conventional cholera therapies in parallel to decrease the morbidity and mortality rate in the developing countries. The paramount objective of this review essentially focuses on the different Quorum Sensing (QS) regulatory switches governing virulence and pathogenicity of Vibrio cholerae. This review also provides an insight into the plausible QS targets that could be exploited to bring about a breakthrough to the prevailing cholera therapy.

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CsrA and three redundant small RNAs regulate quorum sensing in Vibrio cholerae

Cited by 297 publications

References 48 publications

Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli

Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli

The VarS/VarA two-component system modulates the activity of the Vibrio cholerae quorum-sensing transcriptional regulator HapR

Meddling Vibrio cholerae Murmurs: A Neoteric Advancement in Cholera Research

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