Abstract

The facultative pathogen Vibrio cholerae transitions between its human host and aquatic reservoirs where it colonizes chitinous surfaces. Growth on chitin induces expression of chitin utilization genes, genes involved in DNA uptake by natural transformation, and a type VI secretion system that allows contact-dependent killing of neighboring bacteria. We have previously shown that the transcription factor CytR, thought to primarily regulate the pyrimidine nucleoside scavenging response, is required for natural competence in V. cholerae. Through high-throughput RNA sequencing (RNA-seq), we show that CytR positively regulates the majority of competence genes, the three type VI secretion operons, and the four known or predicted chitinases. We used transcriptional reporters and phenotypic analysis to determine the individual contributions of quorum sensing, which is controlled by the transcription factors HapR and QstR; chitin utilization that is mediated by TfoX; and pyrimidine starvation that is orchestrated by CytR, toward each of these processes. We find that in V. cholerae, CytR is a global regulator of multiple behaviors affecting fitness and adaptability in the environment.

Highlights

  • Vibrio cholerae is the causative agent of the diarrheal disease cholera and occupies a range of freshwater and marine environments

  • CytR is a global regulator in Vibrio cholerae In Escherichia coli, the cytidine repressor CytR negatively regulates a small set of pyrimidine nucleoside scavenging and metabolism genes, including uridine dephosphorylase, udp [17]

  • We find that CytR is required for expression of the majority of known competence genes, the three Type VI secretion system (T6SS) clusters, and four known chitinase genes (Fig 1B)

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Summary

Introduction

Vibrio cholerae is the causative agent of the diarrheal disease cholera and occupies a range of freshwater and marine environments. The bacterium has been found in association with plants, algae, cyanobacteria, fish, and marine and freshwater invertebrates [1] and its attachment to copepods has been implicated in disease transmission [2]. When V. cholerae associates with chitin, in addition to chitin utilization enzymes, it produces a DNA uptake apparatus for natural transformation [4]. Components of this apparatus include a pilus that extends into the extracellular environment as well as inner and outer membrane channels that transport DNA molecules into the cytoplasm where it can recombine, allowing horizontal gene transfer [5, 6]. It was recently discovered that in V. cholerae, growth on PLOS ONE | DOI:10.1371/journal.pone.0138834 September 24, 2015

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