Barrasso, K. | bioRxiv Science

bioRxiv2021

Impact of a human gut microbe on Vibrio cholerae host colonization through biofilm enhancement

Recent studies indicate that the human intestinal microbiota could impact the outcome of infection by Vibrio cholerae, the etiological agent of the diarrheal disease cholera. A commensal bacterium, Paracoccus aminovorans, was previously identified in high abundance in stool collected from individuals infected with V. cholerae when compared to stool from uninfected persons. However, if and how P. aminovorans interacts with V. cholerae has not been experimentally determined; moreover, whether any association between this bacterium alters the behaviors of V. cholerae to affect the disease outcome is unclear. Here we show that P. aminovorans and V. cholerae together form dual-species biofilm structures at the air-liquid interface, with previously uncharacterized novel features. Importantly, the presence of P. aminovorans within the murine small intestine enhances V. cholerae colonization in the same niche that is dependent on the Vibrio exopolysaccharide (VPS) and other major components of mature V. cholerae biofilm. These studies illustrate that dual-species biofilm formation is a plausible mechanism used by a gut microbe to increase the virulence of the pathogen, and this interaction may alter outcomes in enteric infections. Significance StatementWhile ample evidence suggests that the outcome of some enteric infections can be affected by the intestinal microbiota, how specific gut microbes change the behaviors of a pathogen is unclear. Here we characterize the interaction between Vibrio cholerae and Paracoccus aminovorans, a gut microbe known to increase in abundance in the intestines during active V. cholerae infection in humans. These two bacteria form a dual-species biofilm structure at the air-liquid interface, and the gut microbe increases the host colonization efficiency of V. cholerae. Importantly, our study identifies a previously unknown mechanism of gut microbe-pathogen interaction that has the potential to alter the disease outcome.

microbiology↗

bioRxiv2019

Ethanolamine regulates CqsR quorum-sensing signaling in Vibrio cholerae

The pathogen that causes cholera, Vibrio cholerae, uses the cell-cell communication process known as quorum sensing (QS) to regulate virulence factor production and biofilm formation in response to changes in population density and complexity. QS is mediated through the detection of extracellular chemical signals called autoinducers. Four histidine kinases, LuxPQ, CqsS, CqsR and VpsS, have been identified as receptors to activate the key QS regulator LuxO at low cell density. At high cell density, detection of autoinducers by these receptors leads to deactivation of LuxO, resulting in population-wide gene expression changes. While the cognate autoinducers that regulate the activity of CqsS and LuxQ are known, the signals that regulate CqsR have not been determined. Here we show that the common metabolite ethanolamine specifically interacts with the ligand-binding CACHE domain of CqsR in vitro and induces the high cell-density QS response through CqsR kinase inhibition in V. cholerae cells. We also identified residues in the CqsR CACHE domain important for ethanolamine detection and signal transduction. Moreover, mutations disrupting endogenous ethanolamine production in V. cholerae delay the onset of, but do not abolish, the high cell-density QS gene expression. Finally, we demonstrate that modulation of CqsR QS response by ethanolamine occurs inside animal hosts. Our findings suggest that V. cholerae uses CqsR as a dual-function receptor to integrate information from the self-made signals as well as exogenous ethanolamine as an environmental cue to modulate QS response.\n\nIMPORTANCEMany bacteria use quorum sensing to regulate cellular processes that are important for their survival and adaptation to different environments. Quorum sensing usually depends on the detection on chemical signals called autoinducers made endogenously by the bacteria. We show here ethanolamine, a common metabolite made by various bacteria and eukaryotes, can modulate the activity of one of the quorum-sensing receptors in Vibrio cholerae, the etiological agent of the disease cholera. Our results raise the possibility that V. cholerae or other quorum-sensing bacteria can combine environmental sensing and quorum sensing to control group behaviors.

microbiology↗