VIRULENCE ASSOCIATED TRAITS & LEGIONELLA PATHOGENESIS

嗜肺军团菌的致病机制 一种叫做军团病的急性有时致命的肺炎 疾病，大概是由有毒的L. 嗜肺菌在宿主巨噬细胞内生存和繁殖。 无毒湖嗜肺菌，其容易通过传代分离， Mueller-Hinton琼脂培养基在 巨噬细胞 最近的研究旨在辨别差异 等基因强毒与无毒L.嗜肺性 有毒的L.嗜肺菌通过寄生虫进入宿主细胞 直接机制涉及表面蛋白质结构的 细菌。 至少有八种表面蛋白抗原与 与毒力菌株，并像定向摄取表型， 失去了L。在体外培养嗜肺菌。 的作用 诱导摄取表型和毒性相关表面 蛋白质在发病机制中的作用尚不清楚，但据认为， 毒力相关性状可能影响细胞内的命运， L.嗜肺菌 这项研究计划的目标是 确定定向吸收的贡献和相关的 表面蛋白抗原与发病机制的关系。 这将是 通过1）分离与毒力有关的基因来完成 相关表型和表征基因产物 表达，2）将毒力相关基因转移到 同基因无毒对应物以试图恢复毒性， 和3）体外诱变毒力相关基因， 基因置换，从野生型亲本构建菌株 只缺少一个功能性基因。 描述的变种人 然后将在适当的体外和动物模型中进行测试， 评估定向摄取表型的作用， 表面蛋白表达与细胞内存活相关 和发病机制。

The pathogenesis of Legionella pneumophila, the etiological agent of the acute and sometimes fatal pneumonia called Legionnaires' disease, is presumably mediated by the ability of virulent L. pneumophila to survive and multiply within host macrophages. Avirulent L. pneumophila, which are easily isolated by passage on Mueller-Hinton agar medium are readily degraded within macrophages. Recent studies aimed at discerning differences between isogenic virulent and avirulent L. pneumophila indicated that virulent L. pneumophila enter host cells by a parasite directed mechanism involving surface protein structure of the bacterium. At least eight surface protein antigens are associated with virulent strains and, like the directed uptake phenotype, are lost when L. pneumophila is cultured in vitro. The role of the induced uptake phenotype and the virulence-associated surface proteins in pathogenesis is not known but it is thought that these virulence associated traits may influence the intracellular fate of L. pneumophila. The goal of this research proposal is to determine the contribution of directed uptake and the associated surface protein antigen to pathogenesis. This will be accomplished by 1) isolating the genes involved in the virulence associated phenotypes and characterizing the products of gene expression, 2) transferring the virulence associated genes to the isogenic avirulent counterpart in an attempt to restore virulence, and 3) mutagenizing the virulence associated gene in vitro and, by gene replacement, constructing strains from wild type parents that lack only a single functional gene. The mutants described will then be tested in appropriate in vitro and animal models to assess the role of the directed uptake phenotype and the associated expression of surface proteins to intracellular survival and pathogenesis.