The VieB auxiliary protein negatively regulates the VieSA signal transduction system in Vibrio cholerae.

Stephanie L Mitchell,Ayman M Ismail,Andrew Camilli,Sophia A Kenrick

doi:10.1186/s12866-015-0387-7

Stephanie L Mitchell, Ayman M Ismail + Show 2 more

Open Access

https://doi.org/10.1186/s12866-015-0387-7

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Abstract

BackgroundVibrio cholerae is a facultative pathogen that lives in the aquatic environment and the human host. The ability of V. cholerae to monitor environmental changes as it transitions between these diverse environments is vital to its pathogenic lifestyle. One way V. cholerae senses changing external stimuli is through the three-component signal transduction system, VieSAB, which is encoded by the vieSAB operon. The VieSAB system plays a role in the inverse regulation of biofilm and virulence genes by controlling the concentration of the secondary messenger, cyclic-di-GMP. While the sensor kinase, VieS, and the response regulator, VieA, behave similar to typical two-component phosphorelay systems, the role of the auxiliary protein, VieB, is unclear.ResultsHere we show that VieB binds to VieS and inhibits its autophosphorylation and phosphotransfer activity thus preventing phosphorylation of VieA. Additionally, we show that phosphorylation of the highly conserved Asp residue in the receiver domain of VieB regulates the inhibitory activity of VieB.ConclusionTaken together, these data point to an inhibitory role of VieB on the VieSA phosphorelay, allowing for additional control over the signal output. Insight into the function and regulatory mechanism of the VieSAB system improves our understanding of how V. cholerae controls gene expression as it transitions between the aquatic environment and human host.

Highlights

Vibrio cholerae is a facultative pathogen that lives in the aquatic environment and the human host
VieB is a dose-dependent inhibitor of VieA-His6 phosphorylation Since many other described auxiliary proteins of two-component systems (TCS) negatively modulate their cognate TCS, we hypothesized that VieB functions as an inhibitor of the VieSA TCS
To test this we examined the effect of VieB on phosphotransfer between glutathione S-transferase (GST)-VieS-C (GST-tagged cytoplasmic portion of VieS) and VieA-His6

Summary

Introduction

Vibrio cholerae is a facultative pathogen that lives in the aquatic environment and the human host. One way V. cholerae senses changing external stimuli is through the three-component signal transduction system, VieSAB, which is encoded by the vieSAB operon. Vibrio cholerae is a human small intestinal pathogen that causes profuse secretory diarrhea and vomiting leading to severe dehydration, which if left untreated can result in death. Translocation of CT into the epithelial cells lining the small intestine leads to profuse secretory diarrhea and results in the exit of V. cholerae from the host back into the aquatic environment [1,2,3,4]. V. cholerae has served as a model organism for studying signal transduction and regulation of virulence genes. One way V. cholerae senses changing environments is through the VieSAB signal transduction system, which was previously discovered through a genetic screen for virulence gene regulators [12].

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