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

鱿鱼-弧菌共生中群体信号串扰的分析

• 批准号: 8603305
• 负责人: Timothy Miyashiro
• 金额: $ 24.9万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2016-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8603305
• 关键词: Address; Adolescent; Animals; Award; Bacteria; Behavior; Benign; Biochemical; Biological; Biological Models; Cells; Chemicals; Chronic; Communication; Complement; Complex; Confocal Microscopy; Development; Employee Strikes; Environment; Epithelial; Gastrointestinal tract structure; Gene Expression; Genes; Genetic; Hawaiian population; Health; Homeostasis; Horizontal Disease Transmission; Human; Hybrids; Immune response; Immune system; Infection; Infectious Agent; Institution; Interdisciplinary Study; Investigation; Laboratories; Light; Marines; Mentorship; Microbe; Modeling; Molecular; Mucins; Mucous body substance; Mutation; Nature; Organ; Organism; Outcome; Phosphotransferases; Plants; Population; Process; Proteins; Regulatory Pathway; Regulon; Research; Research Design; Research Personnel; Role; Seawater; Signal Transduction; Signaling Protein; Squid; Surface; Symbiosis; System; Testing; Tissues; Vibrio; Vibrio cholerae; Vibrio fischeri; Vibrio vulnificus; Vibrionaceae; Virulence Factors; base; computerized data processing; design; hatching; insight; member; microbial; pathogen; post-doctoral training; prevent; programs; quorum sensing; research study; response; sensor; success

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.

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。探索宿主慢性感染的基本原理 上皮组织中的有益微生物，我一直在研究它们之间的互惠共生 海洋细菌费氏弧菌和夏威夷鱿鱼Euprymna scolope。尤其是，我 重点研究了费氏弧菌的LuxU-Luxo信号系统，即 在弧菌科的所有成员中都保守，包括霍乱弧菌和弧菌等病原体。 创伤。虽然这个信号系统调节致病弧菌的毒力因子，但我的 目前的研究表明，LUXU-LUXO信号对费氏弧菌的建立也很重要 与鱿鱼的共生关系。最近，我发现多个传感器蛋白相互作用 LuxU-Luxo调节通路，表明一个复杂的信号网络控制着 细菌定植相关基因的表达。在这里，我建议研究这种形式的 信号串扰，因为它在本质上起作用。具体地说，我计划系统地描述 从遗传和生化角度研究鲁克素与感受器蛋白的相互作用 接近了。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 相应的规则。最后，我将确定由LuxU-Luxo系统发出的信号 对宿主粘液分泌有影响，这种影响在费氏弧菌成功定殖后终止 鱿鱼。这个K99奖项将使我能够完成我的博士后培训 爱德华·鲁比博士和玛格丽特·麦克福尔-倪博士的指导，所以我可能会推出一个全面的 跨学科研究计划，将宿主与微生物的相互作用作为一个独立的 一家大型研究机构的调查员。