Vibrio cholerae quorum sensing as an intestinal symbiosis factor in a model arthropod host

Abstract/Project Summary Vibrio cholerae is a human diarrheal pathogen and an environmental organism that persists in the arthropod intestine. Our preliminary results suggest that the V. cholerae high cell density quorum sensing regulator HapR orchestrates the metabolic transition of this microbe from intestinal pathogen to intestinal symbiont by extending host life span, activating host innate immunity and epithelial repair mechanisms, and promoting host metabolic homeostasis. Here we use the powerful genetics of the model arthropod Drosophila melanogaster to understand the lines of communication between host and pathogen that underlie this transition. We will identify bacterial metabolites that activate host innate immunity and trace the host pathways that are co-opted by the bacterium for this purpose. We will determine whether the arthropod intestinal mucus or peritrophic membrane supports growth of V. cholerae and whether digestion by HapR-activated degradative enzymes activates peritrophic membrane synthesis. Finally, we will explore the role of V. cholerae-derived tryptophan in promoting host metabolic homeostasis. These studies not only expand our appreciation of the role of V. cholerae HapR in the host-pathogen interaction but also provide a new paradigm of quorum sensing control of the host-microbe symbiosis.