Bile Salts And Alkaline Ph Reciprocally Modulate The Interaction Between The Periplasmic Domains Of Vibrio Cholerae Toxr And Toxs

Abstract

ToxR is a transmembrane transcription factor that is essential for virulence gene expression and human colonization by Vibrio cholerae. ToxR requires its operon partner ToxS, a periplasmic integral membrane protein, for full activity. These two proteins are thought to interact through their respective periplasmic domains, ToxRp and ToxSp. In addition, ToxR is thought to be responsive to various environmental cues, such as bile salts and alkaline pH, but how these factors influence ToxR is not yet understood. Using NMR and reciprocal pull down assays, we present the first direct evidence that ToxR and ToxS physically interact. Furthermore, using NMR and DSF, it was shown that the bile salts cholate and chenodeoxycholate interact with purified ToxRp and destabilize it. Surprisingly, bile salt destabilization of ToxRp enhanced the interaction between ToxRp and ToxSp. In contrast, alkaline pH, which is one of the factors that leads to ToxR proteolysis, decreased the interaction between ToxRp and ToxSp. Taken together, these data suggest a model whereby bile salts or other detergents destabilize ToxR, increasing its interaction with ToxS to promote full ToxR activity. Subsequently, as V. cholerae alkalinizes its environment in late stationary phase, the interaction between the two proteins decreases, allowing ToxR proteolysis to proceed.

Publication Date

7-1-2017

Publication Title

Molecular Microbiology

Volume

105

Issue

2

Number of Pages

258-272

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1111/mmi.13699

Socpus ID

85019227592 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/85019227592

This document is currently not available here.

Share

COinS