REQUIREMENTS FOR BACTERIAL COLONIZATION OF ANIMAL TISSUE

我们研究的长期目标是确定允许细菌与宿主交流的信号 并确定它们对宿主环境作出反应的途径。共生协会 夏威夷鱿鱼Euprymna speakopes和它的细菌伙伴Vibrio fischeri之间的关系，提供了一个 简单，优雅的模型系统，用于研究细菌与动物的相互作用。只有V.fischeri殖民鱿鱼。 迄今为止的证据表明，V.fischeri积极参与了观察到的特异性， 协会然而，决定这种特异性的因素还不清楚。我们已经确定了一 费氏弧菌启动共生所需的基因簇（syp，共生多糖位点）， 和控制syp转录的未连接的传感激酶调节因子rscS。四个额外的监管机构是 提出或已知也控制syp转录，包括α 1依赖性反应调节因子，SypG， 和2个额外的双组分调节器。因此，syp由至少3种蛋白质控制，预测它们 对环境的感知和反应。特定等位基因（rscS*）的多拷贝表达导致费氏弧菌 表达与改变的细胞-细胞相互作用一致的syp依赖性新表型：褶皱集落 对固体复合培养基和液体基本培养基中的膜形成的影响。 控制syp转录的调节机制，并鉴定与syp相关的其他基因。 依赖表型我们将鉴定由syp基因座产生的多糖，并鉴定任何 细胞表面性质的差异。最后，我们将更详细地研究共生的本质 缺陷的syp突变体，并探讨可能的解释，以占它。实验提出了这里 将扩大我们对殖民化如何启动以及信号交换如何发生的理解。 原核生物和真核生物在建立长期关联的过程中。与公众的相关性 健康在于这个模型系统的潜力，以揭示新的机制，细菌与 动物宿主这些信息可能有助于设计新的抗菌剂。我们 研究微生物与引起人类胃肠炎的细菌密切相关， 病原体，副溶血性弧菌和创伤弧菌。研究这一模型也可能导致一些方法， 预防、减少或治疗此类感染。

The long-term objective of our research is to define signals that allow bacteria to communicate with a host and to identify the pathways by which they respond to the host environment. The symbiotic association between the Hawaiian squid, Euprymna scolopes, and its bacterial partner, Vibrio fischeri, provides a simple, elegant model system for studying bacteria-animal interactions. Only V.fischeri colonizes the squid. The evidence to date suggests that V.fischeri actively participates in achievingthe observed specificity of the association. The factors that dictate this specificity, however, are not yet understood. We have identified a cluster of genes (syp, symbiosis polysaccharide locus) that is required for V. fischeri to initiate symbiosis, and an unlinked sensor kinase regulator, rscS, that controls syp transcription. Four additional regulators are proposed or known to also control syp transcription, including a a^-dependent response regulator, SypG, and 2 additional 2-component regulators. Thus, syp is controlled by at least 3 proteins that are predicted to sense and respond to the environment. Multi-copy expression of a particular allele (rscS*) causes V.fischeri to express syp-dependent novel phenotypes consistent with altered cell-cell interactions: wrinkled colonies on solid complex media and pellicle formation in liquid minimal medium.Wepropose to elucidate the major regulatory mechanisms controlling syp transcription and identify additional genes associated with syp- dependent phenotypes. We will identify the polysaccharide produced by the syp locus and identify any differences in cell surface properties. Finally, we will examine in more detail the nature of the symbiosis defect of syp mutants and explore possible explanations to account for it. The experiments proposed here will expand our understanding of how colonization is initiated and how signal exchange occurs between a prokaryote and a eukaryote during the establishment of a long-term association. The relevance to public health lies in the potential of this model system to reveal novel mechanisms by which bacteria interact with an animal host. Such information could potentially allow the design of new antimicrobial agents. Our research organism is closely related to bacteria that cause gastroenteritis in humans, includingthe emerging pathogens, V.parahaemolyticus and V. vulnificus. Studying this model may also lead to approaches that prevent, reduce or treat such infections.