Vibrio Virulence Determinants in a Benign Colonization

描述(申请人提供)：这项研究的长期目标是确定有益细菌对动物上皮组织定植的遗传学和细胞学特征。发光细菌费氏弧菌对鱿鱼发光器官的特殊共生感染将被用作解决这些目标的模式系统。最近的研究集中在利用新孵化的、未定居的幼体和共生的成年鱿鱼来表征这种联系的发起和持续的事件。实验使用细菌突变体和宿主细胞事件来操纵和分析宿主和细菌相互识别的复杂的信号和响应序列。最近开发的基因组工具，包括基于费斯切里弧菌基因组序列的细菌和宿主微阵列以及13,000个成员的鱿鱼EST基因库，为理解这种有益关联的发起和持续的遗传机制提供了一个特殊的机会。拟议的研究计划包括3个具体目标： 1.研究细菌第一次与宿主接触时相互信号活动的作用 2.了解共生菌与宿主吞噬细胞和上皮细胞的相互作用 3.确定驱动共生体逐日排泄和再生长的机制。 该系统既是有益弧菌感染的模型，也是致病弧菌感染的模型，也是弧菌毒力进化的模型。具体地说，基因组比较已经揭示了共同的殖民/毒力因素对共生菌和病原体都很重要。这里提出的工作还将提供新的信息，说明与水生无脊椎动物的特定、稳定的联系如何可能成为人类致病弧菌物种的环境储藏库。

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.