The quorum sensing transcription factor AphA directly regulates natural competence in Vibrio cholerae.

James R J Haycocks,David C Grainger,Gemma Z L Warren,Triana N Dalia,Ankur B Dalia,Jennifer L Chlebek,Lucas M Walker

doi:10.1371/journal.pgen.1008362

James R J Haycocks, David C Grainger + Show 5 more

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https://doi.org/10.1371/journal.pgen.1008362

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Abstract

Many bacteria use population density to control gene expression via quorum sensing. In Vibrio cholerae, quorum sensing coordinates virulence, biofilm formation, and DNA uptake by natural competence. The transcription factors AphA and HapR, expressed at low and high cell density respectively, play a key role. In particular, AphA triggers the entire virulence cascade upon host colonisation. In this work we have mapped genome-wide DNA binding by AphA. We show that AphA is versatile, exhibiting distinct modes of DNA binding and promoter regulation. Unexpectedly, whilst HapR is known to induce natural competence, we demonstrate that AphA also intervenes. Most notably, AphA is a direct repressor of tfoX, the master activator of competence. Hence, production of AphA markedly suppressed DNA uptake; an effect largely circumvented by ectopic expression of tfoX. Our observations suggest dual regulation of competence. At low cell density AphA is a master repressor whilst HapR activates the process at high cell density. Thus, we provide deep mechanistic insight into the role of AphA and highlight how V. cholerae utilises this regulator for diverse purposes.

Highlights

Vibrio cholerae colonises two distinct habitats; the human intestine and aquatic ecosystems [1]
We show that a “switch” within the microbial cell, known to activate disease processes in the human host, controls DNA uptake
Regulation of natural competence in Vibrio cholerae evenly; 27% were located within a 0.5 Mbp section of chromosome II accounting for only 12% of the total genome (Fig 1A, right arm of chromosome II)

Summary

Introduction

Vibrio cholerae colonises two distinct habitats; the human intestine and aquatic ecosystems [1]. The microbe forms biofilms on chitinous surfaces [2,3]. This induces expression of the gene regulatory protein TfoX [4,5,6,7]. Biofilms disperse upon entering the human gut [1,15]. This triggers the expression of virulence factors. The toxin co-regulated pilus (TCP) and cholera toxin (CT) are produced [16]. These factors are encoded by the tcpPH and ctxAB operons respectively

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