Vibrio Virulence Determinants in a Benign Colonization

描述（由申请人提供）：本研究的长期目标是确定表征有益细菌在动物上皮组织中定植的遗传和细胞事件。发光细菌费氏弧菌的鱿鱼Euprymna的发光器官的特定共生感染将被用作一个模型系统，通过它来解决这些目标。最近的调查集中在事件特征的启动和持久性的协会使用新孵化的，未殖民化的青少年，和共生的成年鱿鱼。实验使用细菌突变体和宿主细胞事件来操纵和测定宿主和细菌相互识别的信号和反应的复杂序列。最近开发的基因组工具，包括基于V. fischeri基因组序列的细菌和宿主微阵列和13，000个成员的鱿鱼EST基因文库，为了解这种有益关联的启动和持续的遗传机制提供了一个难得的机会。拟议的研究计划包括三个具体目标： 1.研究细菌首次接触宿主时相互信号活动的作用 2.了解共生体与宿主吞噬细胞和上皮细胞之间的相互作用 3.以确定驱动共生体每日排出和再生的机制。 该系统作为有益和致病性弧菌感染以及弧菌毒力进化的模型。具体来说，基因组比较已经揭示了共同的殖民/毒力因子重要的共生体和病原体。这里提出的工作也将提供新的信息，具体的，稳定的协会与水生无脊椎动物可能作为人类致病性弧菌物种的环境水库。

DESCRIPTION (provided by applicant): The long-term objectives of this research are to define the genetic and cellular events that characterize colonization of animal epithelial tissue by beneficial bacteria. The specific 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 through which to address these objectives. Recent investigations have centered on the events characterizing the initiation and persistence of the association using newly hatched, uncolonized juveniles, and symbiotic adult squid. Experiments use bacterial mutants and host cellular events to manipulate and assay the complex succession of signaling and responses by which the host and bacterium recognize each other. Recently developed genomic tools, including bacterial and host microarrays based on the V. fischeri genome sequence and a 13,000 member squid EST gene library, provide an exceptional opportunity to understand the genetic mechanisms underlying the initiation and persistence of this beneficial association. The proposed research plan integrates 3 specific aims: 1. To examine the role of reciprocal signaling activities as the bacterium first encounters the host 2. To understand the interactions between the symbionts and host phagocytes and epithelial cells 3. To determine the mechanisms driving the daily expulsion and regrowth of the symbionts. This system serves as a model of both beneficial and pathogenic Vibrio infection, as well as the evolution of virulence in vibrios. Specifically, genomic comparisons have already revealed shared colonization/virulence factors important to both symbionts and pathogens. The work proposed here will also provide new information about how specific, stable associations with aquatic invertebrates may serve as environmental reservoirs for human pathogenic Vibrio species.