Submitted for publication (PrePrint)
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.
Watve, Samit; Barrasso, Kelsey; Jung, Sarah A.; Davis, Kristen J.; Hawver, Lisa A.; Khataokar, Atul; Palaganas, Ryan G.; Neiditch, Matthew B.; Perez, Lark; and Ng, Wai-Leung, "Ethanolamine regulates CqsR quorum-sensing signaling in Vibrio cholerae" (2019). Faculty Scholarship for the College of Science & Mathematics. 195.
Samit Watve, Kelsey Barrasso, Sarah A. Jung, Kristen J. Davis, Lisa A. Hawver, Atul Khataokar, Ryan G. Palaganas, Matthew B. Neiditch, Lark J. Perez, & Wai-Leung Ng. (2019). Ethanolamine regulates CqsR quorum-sensing signaling in Vibrio cholerae. bioRxiv 589390; doi: https://doi.org/10.1101/589390