COLONIZATION OF EPITHELIUM BY SYMBIOTIC VIBRIO FISCHERI

这项研究的长期目标是定义生化和 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，我们选择了作为榜样 人的发光器官的良性共生感染 乌贼Euprymna被发光细菌FISHERHERI吞噬。这 系统提供了一种简单的、可通过实验访问的研究范例 特定的宿主-细菌相互作用。我们最近的调查显示 集中在以启蒙运动、殖民主义和 共生感染在刚孵化的鱿鱼幼体中的持久性 利用细菌突变体和宿主形态发生过程操纵和 分析复杂的信号和响应序列，通过这些信号和响应 宿主和细菌进行交流。 我们的具体目标是： 1.确定是否需要使用cAMP的能力 费氏弧菌在宿主上皮的成功定植，以及 这一要求的遗传基础可能是。 2.发现其基因受调控的裂殖弧菌定植因子 自动诱导剂积累。 3.检查是否由V.FISHERI CIX-ADALUAL，HVN负责 在宿主上皮细胞中诱导的霍乱毒素样效应 共生殖民。 4.确定宿主将cAMP排泄到阳光中的程度 器官隐窝是对细菌定植的反应。 我们认为这个系统既是良性的，也是致病的 感染，可能是弧菌毒力状态的进化； IS，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霍乱弧菌毒力的趋同 因素，并促进尚未被描述的因素的发现。这部作品 也将有助于我们理解良性的 软体动物组织的定植是人类致病的蓄水池 弧菌物种。 这里概述的工作将是第一批遗传学和分子生物学研究 费氏拟青霉共生的研究。预计 对细菌中可诱导基因的鉴定将导致 搜索协调信号通路的其他组件 细菌定植的起始性、特异性和稳定性 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.