Three autoinducer molecules act in concert to control virulence gene expression in Vibrio cholerae.

Roman Herzog,Kai Papenfort,Kilian Schumacher,Kathrin S Fröhlich,Nikolai Peschek

doi:10.1093/nar/gky1320

Roman Herzog, Kai Papenfort + Show 3 more

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https://doi.org/10.1093/nar/gky1320

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Abstract

Bacteria use quorum sensing to monitor cell density and coordinate group behaviours. In Vibrio cholerae, the causative agent of the diarrheal disease cholera, quorum sensing is connected to virulence gene expression via the two autoinducer molecules, AI-2 and CAI-1. Both autoinducers share one signal transduction pathway to control the production of AphA, a key transcriptional activator of biofilm formation and virulence genes. In this study, we demonstrate that the recently identified autoinducer, DPO, also controls AphA production in V. cholerae. DPO, functioning through the transcription factor VqmA and the VqmR small RNA, reduces AphA levels at the post-transcriptional level and consequently inhibits virulence gene expression. VqmR-mediated repression of AphA provides an important link between the AI-2/CAI-1 and DPO-dependent quorum sensing pathways in V. cholerae. Transcriptome analyses comparing the effect of single autoinducers versus autoinducer combinations show that quorum sensing controls the expression of ∼400 genes in V. cholerae and that all three autoinducers are required for a full quorum sensing response. Together, our data provide a global view on autoinducer interplay in V. cholerae and highlight the importance of RNA-based gene control for collective functions in this major human pathogen.

Highlights

To efficiently interact with their environment, bacteria often work in groups to solve complex tasks
These analyses identified 11 mRNAs showing at least 2.5-fold regulation by VqmR (Table 1)
Gene regulation by quorum sensing (QS) is crucial for virulence factor production and collective functions of various bacterial pathogens, including V. cholerae [26]

Summary

Introduction

To efficiently interact with their environment, bacteria often work in groups to solve complex tasks. In Vibrio cholerae, the causative agent of cholera disease, QS is intimately linked to several collective functions, including biofilm formation [3], type VI secretion [4,5], competence [6,7], phage resistance [8] and virulence gene expression [9]. CAI-1 and AI-2 are synthesized by the CqsA and LuxS enzymes and accumulate to concentrations of ∼0.3 ␮M (CAI-1) and ∼1–2 ␮M (AI-2) in cell-free supernatants of Vibrio species [10,11]. Their cognate receptors are the membrane-bound proteins CqsS and LuxPQ, respectively [11,12,13,14,15,16]. Two other receptor proteins, CqsR and VpsS, have been reported to channel information through LuxO, indicating the existence of at least four sensory inputs for this pathway [21]

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