Genome-wide mapping of Vibrio cholerae VpsT binding identifies a mechanism for c-di-GMP homeostasis

Thomas Guest, James R J Haycocks, Gemma Z L Warren, David C Grainger

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Abstract

Many bacteria use cyclic dimeric guanosine monophosphate (c-di-GMP) to control changes in lifestyle. The molecule, synthesized by proteins having diguanylate cyclase activity, is often a signal to transition from motile to sedentary behaviour. In Vibrio cholerae, c-di-GMP can exert its effects via the transcription factors VpsT and VpsR. Together, these proteins activate genes needed for V. cholerae to form biofilms. In this work, we have mapped the genome-wide distribution of VpsT in a search for further regulatory roles. We show that VpsT binds 23 loci and recognises a degenerate DNA palindrome having the consensus 5'-W-5R-4[CG]-3Y-2W-1W+1R+2[GC]+3Y+4W+5-3'. Most genes targeted by VpsT encode functions related to motility, biofilm formation, or c-di-GMP metabolism. Most notably, VpsT activates expression of the vpvABC operon that encodes a diguanylate cyclase. This creates a positive feedback loop needed to maintain intracellular levels of c-di-GMP. Mutation of the key VpsT binding site, upstream of vpvABC, severs the loop and c-di-GMP levels fall accordingly. Hence, as well as relaying the c-di-GMP signal, VpsT impacts c-di-GMP homeostasis.

Original languageEnglish
Pages (from-to)149-159
Number of pages11
JournalNucleic Acids Research
Volume50
Issue number1
Early online date15 Dec 2021
DOIs
Publication statusPublished - 11 Jan 2022

Bibliographical note

© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

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