Analysis of quorum-signaling crosstalk within the squid-vibrio symbiosis

项目摘要 有益微生物对真核生物的整体健康至关重要， 包括人类探讨宿主慢性感染的基本原理 我一直在研究它们之间的互利共生关系 海洋细菌费氏弧菌和夏威夷鱿鱼Euprymna piglopes。我特别 已经专注于表征V. fischeri的LuxU-LuxO信号系统， 在弧菌科的所有成员中保守，包括病原体如霍乱弧菌和弧菌。 创伤。虽然这个信号系统调节致病性弧菌的毒力因子，但我 目前的研究表明，LuxU-LuxO信号传导对于费氏弧菌建立 与乌贼的共生关系最近，我发现多个传感器蛋白与 LuxU-LuxO调节通路，表明一个复杂的信号网络控制着 参与细菌定殖的基因的表达。在这里，我建议审查这种形式的 信号串扰，因为它在自然界中起作用。具体来说，我计划系统地描述 LuxU和传感器蛋白之间的相互作用， 接近。我还将确定哪些传感器蛋白在宿主中是活跃的，并确定它们的 相应的调节子。最后，我将确定是否由LuxU-LuxO系统信令 影响宿主粘液分泌，在费氏弧菌成功定殖后停止分泌 鱿鱼这个K99奖将使我能够完成我的博士后培训下， 爱德华·鲁比博士和玛格丽特·麦克福尔-恩盖博士的指导，所以我可能会推出一个全面的 跨学科研究计划，研究宿主-微生物相互作用作为一个独立的 一家大型研究机构的研究员。

Project Summary Beneficial microbes are essential for the overall health of eukaryotic organisms, including humans. To explore the fundamental principles underlying chronic infections of host epithelial tissue by beneficial microbes, I have been studying the mutualistic symbiosis between the marine bacterium Vibrio fischeri and the Hawaiian squid Euprymna scolopes. In particular, I have focused on characterizing the LuxU-LuxO signaling system of V. fischeri, which is conserved in all members of the Vibrionaceae, including pathogens such as V. cholerae and V. vulnificus. While this signaling system regulates virulence factors in pathogenic vibrios, my current research shows that LuxU-LuxO signaling is also important for V. fischeri to establish the symbiosis with squid. Recently, I have discovered that multiple sensor proteins interact with the LuxU-LuxO regulatory pathway, suggesting that a complex signaling network controls the expression of genes involved in bacterial colonization. Here, I propose to examine this form of signaling crosstalk as it functions in nature. Specifically, I plan to systematically characterize the interactions between LuxU and the sensor proteins using both genetic and biochemical approaches. I will also identify which sensor proteins are active in the host and determine their corresponding regulons. Finally, I will determine whether signaling by the LuxU-LuxO system has an impact on host mucus secretion, which terminates after V. fischeri successfully colonizes the squid. This K99 award will enable me to complete my postdoctoral training under the mentorships of Drs. Edward Ruby and Margaret McFall-Ngai, so I may launch a comprehensive interdisciplinary research program to study host-microbe interactions as an independent investigator at a major research institution.