VIBRIO VIRULENCE DETERMINANTS IN A BENIGN COLONIZATION

描述：(改编自《调查者摘要》)：长期 这项研究的目标是定义生化和遗传事件 这是动物上皮组织细菌定植的特征。这个 乌贼发光器官良性共生感染 发光细菌费氏弧菌的头节将被用作模型 实现这些目标的系统。最近对此的调查 协会都集中在其发起的事件上， 在共生的头48小时内建立和容纳 新孵化的鱿鱼幼鱼的感染。实验方法 这里描述的使用细菌突变体和宿主形态发生指示剂 操纵和分析复杂的信号和响应序列 寄主和细菌在这些阶段进行通信。 殖民进程。 拟议的研究计划包括3个具体目标：(1)确定如何 组织嗜性是由寄主促进的，并被费氏弧菌细胞利用； (2)研究宿主吞噬细胞在这种联系中的作用；及(3) 定义Luxair基因的产物如何调节隐窝的肿胀 上皮细胞和实现正常的定植水平 细菌。 预计这项研究的结果将为我们提供关于 新发现的宿主来源的粘液样结构有助于费氏弧菌 迁移到内部宿主组织，定植细菌如何特异性 逃避宿主免疫系统，以及他们体内的加氧酶活性 荧光素酶既能刺激宿主组织的形态发生，又能提供营养。 该系统既是良性弧菌感染的模型，也是致病性弧菌感染的模型。 也许还有弧菌毒力状态的进化。具体来说， 增强发光器的细菌决定簇的鉴定 共生已经揭示了与已知霍乱弧菌毒力的趋同 因素，以及持续的努力可能会促进尚未描述的 一个。这里提出的工作还将提供关于 文蛤、蜗牛、乌贼和乌贼的特定、稳定的定殖化机制 它们的近亲可能是人类致病的环境宿主。 弧菌物种。

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.