INVASION GENE AND VIRULENCE OF LEGIONELLA

性状（改编自申请人摘要）：嗜肺军团菌 会导致严重的有时致命的肺炎， 疾病 军团病已被证明出现在个人， 长期暴露于来自家庭供水的气溶胶中， 含有军团菌 第一个证据表明，空气处理设备是 感染源源自1976年一次经证实的军团菌流行。 最近出现了大量的感染病例 在游轮上也一样。 约15%的生活用水 被认为含有军团菌 已经发现 军团菌在感染过程中几乎完全在细胞内复制 和环境。 因此，军团菌必须进入真核细胞， 为了生存，参与进入的基因应该是至关重要的， 疾病的生产。 调查人员最近的数据显示， 军团菌生长在环境宿主--阿米巴原虫 Castellani，对宿主细胞的侵入性大约高出2到4个对数 在标准实验室培养基中生长的细菌。 电镜 对入口的检查表明，一种称为“盘绕”的新机制 吞噬作用”负责细菌的摄取。 这种机制似乎 导致军团菌进入活化的 巨噬细胞 总之，这些研究表明，一个关键因素， 在供水中产生的有毒军团菌是在 适当的环境宿主，没有它，研究者假设 人类感染很可能不会发生。 的具体目标 目前的建议是：1）分离和表征参与的基因 2）确定这些基因参与的毒力， 军团菌 通过审查进入机制和 调节它的因素，研究人员希望进一步研究 了解军团菌如何导致疾病，并提供见解 转化为预防疾病的新方法。

DESCRIPTION (Adapted from the applicant's abstract): Legionella pneumophila causes the severe and sometimes lethal pneumonia termed Legionnaire's disease. Legionnaire's disease has been shown to arise in individuals that undergo prolonged exposure to aerosols from domestic water supplies that contain Legionella. The first evidence that air-handling devices were the source of infection stems from a confirmed Legionella epidemic in 1976. There have recently been a large number of infections that have arisen aboard cruise ships as well. Approximately 15% of all domestic water supplies are thought to contain Legionella. It has been found that Legionella replicates almost exclusively intracellularly during infection and in the environment. Thus, Legionella must enter a eukaryotic cell in order to survive and the genes involved in entry should be critical for production of disease. The investigator's recent data indicate that Legionella grown in an environmental host, the amoebae Acanthamoeba castellani, are approximately two to four logs more invasive for host cells than bacteria grown in the standard laboratory medium. Electron microscopic examination of entry has shown that a novel mechanism, termed "coiling phagocytosis", is responsible for bacterial uptake. This mechanism appears to result in enhanced survival of Legionella after entry into activated macrophages. Taken together, these studies indicate that a key factor in the production of virulent Legionella in water supplies is growth within the appropriate environmental host, without which the investigator hypothesizes that human infections will most likely not occur. The specific aims of the current proposal are to: 1) isolate and characterize the genes involved in invasion and 2) determine the involvement of these genes in virulence of Legionella. Through an examination of the mechanisms of entry and the factors that regulate it, the investigator hopes to further the understanding of how Legionella causes disease as well as provide insight into novel methods for disease prevention.