Vibrio cholerae high cell density quorum sensing activates the host intestinal innate immune response

doi:10.1016/j.celrep.2022.111368

Cell Reports

Volume 40, Issue 12, 20 September 2022, 111368

https://doi.org/10.1016/j.celrep.2022.111368 Get rights and content

Under a Creative Commons license

open access

Highlights

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V. cholerae HapR represses pathogen tryptophan consumption
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Host enterocytes convert dietary tryptophan to serotonin
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Intestinal serotonin synthesis activates IMD signaling and prolongs host survival
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HapR orchestrates a commensal interaction between host and pathogen

Summary

Quorum sensing fundamentally alters the interaction of Vibrio cholerae with aquatic environments, environmental hosts, and the human intestine. At high cell density, the quorum-sensing regulator HapR represses not only expression of cholera toxin and the toxin co-regulated pilus, virulence factors essential in human infection, but also synthesis of the Vibrio polysaccharide (VPS) exopolysaccharide-based matrix required for abiotic and biotic surface attachment. Here, we describe a feature of V. cholerae quorum sensing that shifts the host-pathogen interaction toward commensalism. By repressing pathogen consumptive anabolic metabolism and, in particular, tryptophan uptake, V. cholerae HapR stimulates host intestinal serotonin production. This, in turn, activates host intestinal innate immune signaling to promote host survival.

Graphical abstract

Research topic(s)

CP: Microbiology

CP: Immunology

Keywords

Vibrio cholerae

quorum sensing

Drosophila melanogaster intestine

tryptophan metabolism

innate immunity

serotonin

infection

posterior midgut

immune deficiency pathway

antimicrobial peptide

Data and code availability

RNA-seq data for WT V. cholerae and a ΔhapR mutant grown to early stationary phase (NCBI: PRJNA810852) and Drosophila intestines infected with these two strains (NCBI: PRJNA811240) have been deposited in the NCBI repository. No code was generated as a part of these studies. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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⁶: Lead contact