REQUIREMENTS FOR BACTERIAL COLONIZATION OF ANIMAL TISSUE

动物组织细菌定植的要求

• 批准号: 7591183
• 负责人: Karen L Visick
• 金额: $ 27.58万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7591183
• 关键词: Accounting; Address; Alleles; Anabolism; Animal Model; Animals; Area; Bacteria; Biological Models; Cell Communication; Cell surface; Cells; Communication; Complex; Defect; Disease; Environment; Eukaryota; Foundations; Gastroenteritis; Gene Cluster; Gene Targeting; Genes; Genetic; Genetic Transcription; Hawaiian population; Human; Immune response; Infection; Laboratories; Lead; Liquid substance; Mediating; Modification; Nature; Nutrient; Organ; Organism; Pathway interactions; Phase; Phenotype; Phosphotransferases; Physiological; Polysaccharides; Process; Production; Prokaryotic Cells; Proteins; Public Health; Regulatory Pathway; Research; Research Personnel; Role; Seawater; Signal Transduction; Solid; Specificity; Squid; Staging; Study models; Surface; Surface Properties; Symbiosis; Vibrio fischeri; Vibrio vulnificus; Work; animal tissue; antimicrobial drug; design; mutant; novel; pathogen; prevent; programs; research study; response; sensor

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.

我们研究的长期目标是定义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 在夏威夷鱿鱼Euprymna scolope和它的细菌伙伴鱼弧菌之间，提供了 用于研究细菌-动物相互作用的简单、优雅的模型系统。只有费斯切里轮虫在乌贼上定居。 到目前为止的证据表明，费氏弧菌积极参与实现观察到的 协会。然而，决定这种特异性的因素还不清楚。我们已经确定了一个 费氏弧菌启动共生所需的一组基因(SYP，共生多糖基因座)， 以及控制SYP转录的未连接的传感器激酶调节因子RSCs。另外四个监管机构是 建议或已知也控制SYP转录，包括a^依赖的反应调节因子，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，这些蛋白质被预测为 感知并对环境做出反应。特定等位基因(RSCS*)的多拷贝表达可引起裂纹伊蚊 表达与细胞间相互作用改变一致的SYP依赖的新表型：皱纹集落 关于固体复合介质和液体微量介质中膜的形成。 控制SYP转录的调控机制，并确定与SYP相关的其他基因 依赖表型。我们将鉴定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。 SYP突变体的缺陷，并探索可能的解释。这里提出的实验 将扩大我们对殖民是如何启动的以及如何在 原核生物与真核生物期间建立了长期的联合关系。与公众的相关性 健康在于这个模型系统有可能揭示细菌与细菌相互作用的新机制 动物寄主。这些信息可能会使设计新的抗菌剂成为可能。我们的 研究生物体与引起人类胃肠炎的细菌密切相关，包括新兴的 病原菌、副溶血性弧菌和创伤弧菌。研究这一模型也可能导致 预防、减少或治疗此类感染。