SEQUENCING AND CHARACTERIZATION OF THE LEGIONELLA GENOME

描述（改编自研究者摘要）：嗜肺军团菌， 军团病的病原体，是一种细胞内病原体 它在人类巨噬细胞和大多数新鲜的 供水。为了更好地了解它的生命周期和感染模式， 以及它与其他细胞内寄生虫的关系， 将确定序列，并鉴定其所有推定基因。测序 将通过混合BAC鸟枪/全基因组鸟枪策略来完成。基因 将通过先进的计算方法预测功能，包括 系统发育比较 L.将比较嗜肺菌的细胞内生活方式 在各种军团菌和L.嗜肺亚种，以确定 这些基因中潜在的功能基序。这些基因的表达模式 还将在不同生长阶段和模式期间比较基因（例如， 共生与植物）。这将通过北方分析或 使用具有报告基因标签的双功能杂交体。最后，等位基因 交换将用于在某些特定的基因中产生无效突变， 感兴趣的是确定它们在军团菌生命周期方面的功能 以及退伍军人症的发病机制。 军团菌的序列将是研究人员的宝贵资源， 领域完整的军团菌序列分析将为 关于这种生物的进化和生态学的信息，特别是当 与其他已经或正在形成的细菌相比 测序将它的基因组与那些 衣原体、立克次体和分枝杆菌，或艾滋病毒等病毒，也是 胞内病原体最后，在此过程中获得的信息 这项工作应该有助于设计治疗退伍军人症的策略。 疾病，这是致命的，在一个显着的百分比， 感染的人。

DESCRIPTION (Adapted from the Investigator's Abstract): Legionella pneumophila, the causative agent of Legionnaires' Disease, is an intracellular pathogen which reproduces within human macrophages and within amoebae in most fresh water supplies. To better understand its life cycle and mode of infectivity, as well as its relationship to other intracellular parasites, its complete genome sequence will be determined, and all its putative genes identified. Sequencing will be accomplished by a mixed BAC shotgun/whole genome shotgun strategy. Gene functions will be predicted by advanced computational methods, including phylogenetic comparisons. The genes involved in L. pneumophila's intracellular lifestyle will be compared in various Legionella species and L. pneumophila subspecies to determine potential functional motifs in these genes. The expression pattern of these genes will also be compared during different stages and modes of growth (e.g. symbiotic versus vegetative). This will be accomplished by northern analysis or the use of bifunctional hybrids with reporter gene tags. Finally, allelic exchange will be used to produce null mutations in some genes of particular interest to determine their functions with regard to the Legionella life cycle and the pathogenesis of Legionnaires' Disease. The sequence of Legionella will be a valuable resource for researchers in the field. Analysis of the complete Legionella sequence should provide important information on the evolution and ecology of this organism, especially when compared to that of other bacteria already or in the process of being sequenced. It will be especially useful to compare its genome with those of Chlamydia, Rickettsia, and Mycobacteria, or viruses such as HIV, which are also intracellular pathogens. Finally, information obtained in the course of this work should be useful in designing therapeutic strategies for Legionnaires' Disease, which is fatal in a significant percentage of antibiotic-treated infected individuals.