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Vibrio cholerae CsrA Regulates ToxR Levels in Response to Amino Acids and Is Essential for Virulence.

Mey AR, Butz HA, Payne SM - MBio (2015)

Bottom Line: Conversely, specific amino acid substitutions in CsrA were associated with defects in ToxR production in response to NRES.Unlike previously described effects of CsrA on virulence gene regulation, the effects of CsrA on ToxR were not mediated through quorum sensing and HapR.By linking environmental sensing to the ToxR regulon, CsrA effectively acts as a switch that controls pathogenesis in response to specific signals.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biosciences and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, USA armey@austin.utexas.edu.

No MeSH data available.


Related in: MedlinePlus

Overview of the VarA/S-CsrB/C/D-CsrA pathway. Dashed arrows indicate that the exact mechanism of regulation is currently unknown. We show here that CsrA positively regulates the level of ToxR protein in response to amino acids. Var/Csr-mediated regulation of biofilm and virulence gene expression via the quorum sensing pathway is described by Lenz et al. (25). The regulation of omp gene expression by ToxR is well established (8, 10–12, 14).
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fig1: Overview of the VarA/S-CsrB/C/D-CsrA pathway. Dashed arrows indicate that the exact mechanism of regulation is currently unknown. We show here that CsrA positively regulates the level of ToxR protein in response to amino acids. Var/Csr-mediated regulation of biofilm and virulence gene expression via the quorum sensing pathway is described by Lenz et al. (25). The regulation of omp gene expression by ToxR is well established (8, 10–12, 14).

Mentions: Homologs of the VarS/VarA system are found in many bacterial species, including Escherichia coli (BarA/UvrY) and Pseudomonas species (GacS/GacA). These systems regulate processes as diverse as central carbon metabolism, motility, biofilm formation, quorum sensing, production of virulence determinants, and oxidative stress (reviewed in references 21 and 22). In V. cholerae, the VarS/VarA system is involved in carbon metabolism (23), quorum sensing and biofilm formation (24, 25), expression of virulence determinants (26, 27), fitness in infant mice and rabbits (23, 27), and survival in pond water after being shed from the mammalian host (23). VarS is predicted to be a sensor kinase that phosphorylates and activates its cognate response regulator VarA in response to an unknown signal. Activated VarA induces transcription of three noncoding small RNAs (sRNAs), CsrB/C/D (25), which bind the regulatory protein CsrA and sequester it in an inactive state (Fig. 1). Each of the three V. cholerae Csr sRNAs contains multiple CsrA recognition sequences and is predicted to bind 15 to 20 CsrA molecules (25), as has been shown for the CsrA-antagonizing sRNA CsrB in E. coli (28). CsrA is a global, posttranscriptional regulator that acts by binding to mRNA targets and affecting their translation or stability. CsrA is likely the primary target of signaling through the VarS/A system in V. cholerae (25), but it is not known whether the CsrA/B/C/D system is subject to VarS/A-independent regulation.


Vibrio cholerae CsrA Regulates ToxR Levels in Response to Amino Acids and Is Essential for Virulence.

Mey AR, Butz HA, Payne SM - MBio (2015)

Overview of the VarA/S-CsrB/C/D-CsrA pathway. Dashed arrows indicate that the exact mechanism of regulation is currently unknown. We show here that CsrA positively regulates the level of ToxR protein in response to amino acids. Var/Csr-mediated regulation of biofilm and virulence gene expression via the quorum sensing pathway is described by Lenz et al. (25). The regulation of omp gene expression by ToxR is well established (8, 10–12, 14).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526715&req=5

fig1: Overview of the VarA/S-CsrB/C/D-CsrA pathway. Dashed arrows indicate that the exact mechanism of regulation is currently unknown. We show here that CsrA positively regulates the level of ToxR protein in response to amino acids. Var/Csr-mediated regulation of biofilm and virulence gene expression via the quorum sensing pathway is described by Lenz et al. (25). The regulation of omp gene expression by ToxR is well established (8, 10–12, 14).
Mentions: Homologs of the VarS/VarA system are found in many bacterial species, including Escherichia coli (BarA/UvrY) and Pseudomonas species (GacS/GacA). These systems regulate processes as diverse as central carbon metabolism, motility, biofilm formation, quorum sensing, production of virulence determinants, and oxidative stress (reviewed in references 21 and 22). In V. cholerae, the VarS/VarA system is involved in carbon metabolism (23), quorum sensing and biofilm formation (24, 25), expression of virulence determinants (26, 27), fitness in infant mice and rabbits (23, 27), and survival in pond water after being shed from the mammalian host (23). VarS is predicted to be a sensor kinase that phosphorylates and activates its cognate response regulator VarA in response to an unknown signal. Activated VarA induces transcription of three noncoding small RNAs (sRNAs), CsrB/C/D (25), which bind the regulatory protein CsrA and sequester it in an inactive state (Fig. 1). Each of the three V. cholerae Csr sRNAs contains multiple CsrA recognition sequences and is predicted to bind 15 to 20 CsrA molecules (25), as has been shown for the CsrA-antagonizing sRNA CsrB in E. coli (28). CsrA is a global, posttranscriptional regulator that acts by binding to mRNA targets and affecting their translation or stability. CsrA is likely the primary target of signaling through the VarS/A system in V. cholerae (25), but it is not known whether the CsrA/B/C/D system is subject to VarS/A-independent regulation.

Bottom Line: Conversely, specific amino acid substitutions in CsrA were associated with defects in ToxR production in response to NRES.Unlike previously described effects of CsrA on virulence gene regulation, the effects of CsrA on ToxR were not mediated through quorum sensing and HapR.By linking environmental sensing to the ToxR regulon, CsrA effectively acts as a switch that controls pathogenesis in response to specific signals.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biosciences and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, USA armey@austin.utexas.edu.

No MeSH data available.


Related in: MedlinePlus