INVASION GENE AND VIRULENCE OF LEGIONELLA

描述(改编自申请者摘要)：嗜肺军团菌 引起称为军团肺炎的严重肺炎，有时甚至是致命性肺炎 疾病。军团病已被证明出现在 长期暴露在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 感染源源于1976年确认的军团菌疫情。 最近出现了大量的感染 在游轮上也是如此。约占所有生活用水的15% 供应品被认为含有军团菌。已经发现， 军团菌在感染期间几乎完全在细胞内复制 在环境中。因此，军团菌必须进入真核细胞 为了生存和参与进入的基因应该是关键的 疾病的产生。调查人员的最新数据表明 军团菌生长在环境宿主棘阿米巴中 Castellani，大约有2到4个对数对宿主细胞更具侵袭性 而不是在标准的实验室培养基中生长的细菌。电子显微镜 对进入的检查表明，一种新的机制，称为“盘绕” 吞噬作用“，负责细菌的吸收。这种机制出现了 导致军团菌进入激活状态后的生存能力增强 巨噬细胞。总而言之，这些研究表明， 供水中有毒军团菌的产量正在增长 合适的环境宿主，如果没有它，调查者就会假设 人类感染极有可能不会发生。《公约》的具体目标 目前的建议是：1)分离和鉴定涉及到 侵袭性和2)确定这些基因参与的毒力 军团菌。通过对进入机制和 监管它的因素，调查人员希望进一步 了解军团菌如何致病，并提供洞察力 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.