VIRULENCE ASSOCIATED TRAITS & LEGIONELLA PATHOGENESIS

病原菌嗜肺军团菌的致病机制 一种称为军团肺炎的急性肺炎，有时甚至是致命的 病原菌的致病能力可能与致病力有关。 嗜肺性肺炎在宿主巨噬细胞内生存和繁殖。 无毒嗜肺性乳杆菌，很容易通过传代分离出来 米勒-辛顿琼脂培养基易在 巨噬细胞。最近旨在辨别差异的研究 在同基因强毒和无毒嗜肺乳杆菌之间 致病性嗜肺性乳杆菌通过寄生虫进入宿主细胞 涉及细菌表面蛋白结构的定向机制 细菌。至少有8种表面蛋白抗原是相关的 与强毒菌株和定向摄取表型一样，是 当嗜肺性乳杆菌在体外培养时丢失。美国政府的角色 诱导摄取表型与毒力相关表面 蛋白质在发病机制中的作用尚不清楚，但人们认为这些 毒力相关性状可能会影响细胞内的命运 嗜肺性乳杆菌。这项研究提案的目标是 确定定向摄取的贡献和相关的 表面蛋白抗原对发病机制的影响。这将是 通过1)分离与毒力有关的基因来完成 基因的相关表型及其产物的表征 表达，2)将毒力相关基因转移到 同基因无毒的对应物试图恢复致病性， 3)在体外诱变毒力相关基因，并通过 基因置换，构建野生型亲本菌株 它只缺少单一的功能基因。突变体描述了 然后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和 表面蛋白的表达与细胞内存活的关系 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.