COLONIZATION OF EPITHELIUM BY SYMBIOTIC VIBRIO FISCHERI

这项研究的长期目标是确定生物化学和 表征动物细菌定植的分子事件 上皮组织 为了实现这一目标，我们选择了 系统的发光器官的良性，共生感染 发光细菌费氏弧菌（Vibrio fischeri）对鱿鱼Euprymna的影响。 这 系统提供了一个简单的，实验上可访问的，研究范式 特定宿主-细菌相互作用。 我们最近的调查 集中在事件特征的启动，殖民化， 新孵化的鱿鱼幼鱼中共生感染的持续性 使用细菌突变体和宿主形态发生过程来操纵和 分析复杂的信号传导和反应序列， 宿主和细菌之间进行交流。 我们的具体目标是： 1. 确定是否需要利用cAMP的能力， 费氏弧菌成功定殖宿主上皮，以及 这种要求的遗传基础可能是。 2. 发现其基因受F. fischeri调控的V. fischeri定植因子 自诱导物积累。 3. 检查V. fischeri Cix-模拟物Hvn是否负责 霍乱毒素样作用，在宿主上皮细胞中诱导， 共生殖民 4. 确定宿主将cAMP排泄到光中的程度 对细菌定植的反应。 我们认为，这个系统可以作为良性和致病的模型， 感染，也许是弧菌毒力状态的进化; 鉴定增强光的细菌和宿主决定因素 器官共生可能揭示与已知的霍乱弧菌毒力的趋同 这些因素，并促进尚未描述的发现。 这项工作 也将有助于我们理解良性肿瘤 软体动物组织的定居作为人类病原体的储存库， 弧菌属。 这里概述的工作将是第一个遗传和分子 研究表明，该菌是一种新的病原菌，双孢菌共生。 预计在 细菌中诱导基因的鉴定将导致 寻找信号通路的其他组成部分， 细菌定殖的起始、特异性和稳定维持 上皮组织。

The long term objectives of this research are to define the biochemical and molecular events that characterize the bacterial colonization of animal epithelial tissue. To accomplish this goal we have chosen as a model system the benign, symbiotic infection of the light-emitting organ of the squid Euprymna scolopes by the luminous bacterium Vibrio fischeri. This system provides a simple, experimentally accessible, paradigm for studying specific host-bacterial interactions. Our recent investigations have centered on the events characterizing the initiation, colonization, and persistence of the symbiotic infection in newly hatched juvenile squids using bacterial mutants and host morphogenic processes to manipulate and assay the complex succession of signaling and responses through which the host and bacterium communicate. Our specific aims are to: 1. Determine whether the ability to utilize cAMP is required for a successful V. fischeri colonization of host epithelium, and what the genetic basis for that requirement may be. 2. Discover V. fischeri colonization factors whose genes are regulated by autoinducer accumulation. 3. Examine whether the V. fischeri Cix-analog, Hvn is responsible for the cholera-toxin like effects that are induced in host epithelia during symbiotic colonization. 4. Determine the extent to which the host excretes cAMP into the light organ crypts in response to bacterial colonization. We believe that this system serves as a model of both benign and pathogenic infection and, perhaps of evolution of the virulence state in vibrios; that is, identification of bacterial and host determinants that potentiate light organ symbiosis may reveal convergences with known V. cholerae virulence factors, and promote the discovery of as yet undescribed ones. This work will also aid our understanding of the mechanisms by which benign colonizations of mollusk tissue serve as a reservoir for human pathogenic Vibrio species. The work outlined here will be among the first genetic and molecular studies of athe V. fischeri- E. scolopes symbiosis. It is expected that the identification of inducible genes in the bacterium will lead to a search for other components of signaling pathways that coordinate initiation, specificity and stable maintenance of a bacterial colonization of epithelial tissues.