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

摘要/项目摘要 霍乱弧菌是一种人类腹泻病原体，也是一种持续存在于节肢动物体内的环境微生物。 肠子。我们的初步结果表明霍乱弧菌高密度群体感应调节因子 HapR通过以下方式协调这种微生物从肠道病原体到肠道共生体的代谢转变 延长宿主寿命，激活宿主先天免疫和上皮修复机制，促进宿主 代谢动态平衡。在这里，我们使用了模式节肢动物黑腹果蝇强大的遗传学 以了解宿主和病原体之间的通信线路，这些线路是这种转变的基础。 我们将识别激活宿主先天免疫的细菌代谢物，并追踪 为此目的而被细菌所选择。我们将确定节肢动物的肠道粘液或 周围膜支持霍乱弧菌的生长及HapR激活的降解物是否消化 酶激活了周围膜的合成。最后，我们将探讨霍乱弧菌衍生的作用 色氨酸在促进宿主代谢稳态中的作用。这些研究不仅扩大了我们对 霍乱弧菌HapR在宿主-病原菌相互作用中的作用也提供了一种新的群体感应范式 控制寄主-微生物共生。

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.