Ethanolamine regulates CqsR quorum-sensing signaling inVibrio cholerae

Abstract

17The pathogen that causes cholera, Vibrio cholerae, uses the cell-cell communication process 18 known as quorum sensing (QS) to regulate virulence factor production and biofilm formation in 19 response to changes in population density and complexity. QS is mediated through the detection 20 of extracellular chemical signals called autoinducers. Four histidine kinases, LuxPQ, CqsS, CqsR 21 and VpsS, have been identified as receptors to activate the key QS regulator LuxO at low cell 22 density. At high cell density, detection of autoinducers by these receptors leads to deactivation of 23 LuxO, resulting in population-wide gene expression changes. While the cognate autoinducers that 24 regulate the activity of CqsS and LuxQ are known, the signals that regulate CqsR have not been 25 determined. Here we show that the common metabolite ethanolamine specifically interacts with 26 the ligand-binding CACHE domain of CqsR in vitro and induces the high cell-density QS response 27through CqsR kinase inhibition in V. cholerae cells. We also identified residues in the CqsR 28 CACHE domain important for ethanolamine detection and signal transduction. Moreover, 29 mutations disrupting endogenous ethanolamine production in V. cholerae delay the onset of, but 30 do not abolish, the high cell-density QS gene expression. Finally, we demonstrate that modulation 31 of CqsR QS response by ethanolamine occurs inside animal hosts. Our findings suggest that V. 32 cholerae uses CqsR as a dual-function receptor to integrate information from the self-made signals 33 as well as exogenous ethanolamine as an environmental cue to modulate QS response. 34 IMPORTANCE 35Many bacteria use quorum sensing to regulate cellular processes that are important for their 36 survival and adaptation to different environments. Quorum sensing usually depends on the 37 detection on chemical signals called autoinducers made endogenously by the bacteria. We show 38 here ethanolamine, a common metabolite made by various bacteria and eukaryotes, can modulate 39 the activity of one of the quorum-sensing receptors in Vibrio cholerae, the etiological agent of the 40 disease cholera. Our results raise the possibility that V. cholerae or other quorum-sensing bacteria 41 can combine environmental sensing and quorum sensing to control group behaviors.42 43 44 Quorum sensing (QS) is used by a wide variety of bacteria to coordinate population-wide 45 changes in behaviors in response to cell density (1). Vibrio cholerae, which causes the diarrheal 46 disease cholera in the human host, uses QS to regulate virulence factor production, biofilm 47 formation, Type VI secretion, metabolic regulation, and natural competence to maintain 48 competitive fitness in various environments (2-10). Four parallel QS signaling systems pathways 49 have been identified in V. cholerae that rely on a phosphorelay to regulate downstream gene 50 expression (11) (Figure 1). At low cell-density (LCD), four histidine kinases CqsS, LuxPQ, CqsR, 51 and VpsS function in parallel to phosphorylate LuxO...

Biofilms by bacterial human pathogens: Clinical relevance - development, composition and regulation - therapeutical strategies

“…CqsA synthesizes the cholera autoinducer 1 (CAI-1), which binds to its cognate membrane-bound receptor CqsS, while LuxS produces the autoinducer 2 (AI-2) binding to the receptor LuxPQ [198]. Recent studies suggest that ethanolamine serves as a ligand for CqsR, while autophosphorylation of VpsS is blocked by nitric oxide via the nitric oxide-responsive hemoprotein NosP [199,200]. Importantly, all four autoinducer receptors feed into the same phosphorelay pathway and converge at the histidine phosphotransfer protein LuxU [198].…”

The Interface of Vibrio cholerae and the Gut Microbiome

“…85,106,107 Ethanolamine is sensed by the CqsR periplasmic CACHE ligand binding domain with high specificity, and addition of ethanolamine repressed Qrr sRNA expression and increased hapR expression leading to inhibition of colonization of the mouse small intestine. 106 Levels of ethanolamine may be controlled and sensed by numerous bacterial pathways. For instance, in pathogens such as enterohaemorrhagic E. coli (EHEC), ethanolamine has been shown to increase virulence gene expression.…”

Pectobacterium carotovorum: agente fitopatógeno causante de la pudrición blanda en la papa (Solanum tuberosum)

“…Además, en Pseudomonas aeruginosa (Schroeter) se ha descrito que regulan la interacción entre especies, así como el medio que la rodea (Abisado et al, 2018;Gurney et al, 2018;McCready et al, 2019;Visick & McFall-Ngai, 2000). Adicionalmente, en Escherichia coli (Escherich) y en Vibrio cholerae Angie Paola, Amaya Guerrero; et al (Pacini) regulan la formación de biofilms, importante en la patogénesis de la enfermedad (Culler et al, 2018;Jemielita et al, 2018;Ng et al, 2019).…”