VIBRIO VIRULENCE DETERMINANTS IN A BENIGN COLONIZATION

描述：（改编自研究者摘要）：长期 这项研究的目的是确定生物化学和遗传事件， 动物上皮组织细菌定植的特征。的 乌贼发光器官的良性共生感染 发光细菌费氏弧菌的寄生虫将被用作模型 为实现这些目标而建立的体系。最近对此的调查 协会集中在事件的特点，其启动， 在共生的头48小时内建立和住宿 感染新孵化的幼鱿鱼。实验方法 使用细菌突变体和宿主形态发生指示剂， 操纵和分析信号和反应的复杂连续性， 宿主和细菌在这些阶段的沟通， 殖民过程。 拟议的研究计划整合了3个具体目标：（1）确定如何 组织嗜性由宿主促进，并被费氏弧菌细胞利用; (2)研究宿主吞噬细胞在联合中的作用;（3） 定义了luxAIR基因的产物是如何介导隐窝肿胀 上皮细胞和正常定植水平的实现， 细菌 预计这项研究的结果将提供洞察如何 一种新发现的宿主来源的粘液样结构促进了费氏弧菌 迁移到内部宿主组织，如何殖民细菌特别是 逃避宿主免疫系统，以及它们的加氧酶活性是否 荧光素酶引起宿主组织形态发生和营养供应。 该系统可作为良性和致病性弧菌感染的模型 也许还能解释弧菌毒力状态的进化。具体地说， 增强发光器官的细菌决定簇的鉴定 共生现象已经显示出与已知的霍乱弧菌毒力的趋同性 因素，并继续努力可能会促进发现尚未描述的 一个这里提出的工作还将提供有关 蛤、蜗牛、鱿鱼和 它们的亲属可能是人类致病菌的环境宿主， 弧菌属。

DESCRIPTION: (Adapted from the Investigator's Abstract): The long term objectives of this research are to define the biochemical and genetic events that characterize the bacterial colonization of animal epithelial tissue. The benign, symbiotic infection of the light-emitting organ of the squid Euprymna scolopes by the luminous bacterium Vibrio fischeri will be used as a model system by which to address these objectives. Recent investigations of this association have centered on the events characterizing its initiation, establishment, and accommodation during the first 48 hours of the symbiotic infection of newly hatched juvenile squids. The experimental approaches described herein use bacterial mutants and host morphogenic indicators to manipulate and assay the complex succession of signalling and responses through which the host and bacterium communicate during these stages of the colonization process. The proposed research plan integrates 3 specific aims: (1) to determine how tissue tropism is facilitated by the host, and exploited by V. fischeri cells; (2) to investigate the role of host phagocytes in the association; and, (3) to define how the products of the luxAIR genes mediate both the swelling of crypt epithelial cells and the achievement of normal colonization levels by the bacteria. It is expected that the results of this research will provide insight into how newly discovered host-derived, mucus-like structures facilitate V. fischeri migration to internal host tissues, how the colonizing bacteria specifically evade the host immune system, and whether the oxygenase activity of their luciferase evokes both host tissue morphogenesis and nutrient provision. This system serves as a model of both benign and pathogenic Vibrio infection and, perhaps, of the evolution of the virulence state in vibrios. Specifically, the identification of bacterial determinants that potentiate light organ symbiosis has already revealed convergences with known V. cholerae virulence factors, and continued efforts may promote the discovery of as yet undescribed ones. The work proposed here will also provide new information about the mechanisms by which specific, stable colonizations of clams, snails, squid and their relatives may serve as environmental reservoirs for human pathogenic Vibrio species.