Comparative Genome Analysis of Leptospira Species

钩端螺旋体病是由钩端螺旋体属中的螺旋体引起的一种世界性人畜共患病。这 疾病现在被认为是全球重要的新兴传染病之一，最新的 发生在尼加拉瓜、巴西、印度、马来西亚、泰国和美国的疫情。临床部 钩端螺旋体病的表现多种多样，从相对轻微的流感样疾病到严重的综合征不等。 与高死亡率相关的多器官感染。拟议研究的最终目标是 增进我们对致病和非致病的基本生物学和遗传差异的了解 钩端螺旋体菌株，采用一系列基于基因组的技术。具体的假设 这一提议背后的原因是，钩端螺旋体菌株具有重大的遗传差异，这可能与 它们的致病能力，以及致病物种改变了适当基因的表达 以应对环境中遇到的变化。因此，我们的目标是增加我们的 应用比较基因组学方法了解钩端螺旋体不同菌株的物种多样性 杂交技术，并了解调控网络(S)控制基因表达，使 钩端螺旋体能够感知并适应作为寄生或自由生活的有机体的生长。具体的 AIMS还旨在通过监测全基因组来研究钩端螺旋体与其宿主之间的相互作用 钩端螺旋体与宿主细胞接触后基因表达的变化及鉴定 在宿主-病原体相互作用过程中差异表达的基因。 加深对钩端螺旋体生物学的了解将为开发应对 这种病原体，也将作为一个模型，以了解基础生物学和致病潜力 新出现的致病物种。

Leptospirosis is a worldwide zoonotic disease that is caused by spirochetes in the genus Leptospira. This disease is now regarded as one of the important emerging infectious diseases worldwide, with the latest outbreaks occurring in Nicaragua, Brazil, India, Malaysia, Thailand and the United States. The clinical manifestations of leptospirosis are varied, ranging from a relatively mild flu-like illness to a severe syndrome of multi-organ infection that is associated with a high mortality. The ultimate goal of the proposed research is to increase our understanding of the basic biology and genetic differences between pathogenic and nonpathogenic strains of Leptospira, employing a range of genome based technologies. The specific hypothesis behind this proposal is that strains of Leptospira have major genetic differences that may be associated with their ability to cause disease, and that the pathogenic species alter the expression of appropriate genes in order to cope with the changes encountered in the environment. As such, we aim to increase our understaning of species diversity of different strains of Leptospira employing comparative genome hybridization techniques, and to understand the regulatory network(s) controlling gene expression that allow Leptospira species to sense and adapt to growth as either a parasitic or free-living organism. The Specific Aims are also designed to study the interaction between Leptospira and its host by monitoring the genomewide changes in leptospiral gene expression upon contact with host cells and to identify and characterize genes that are differentially expressed during host-pathogen interaction. An increased understanding of Leptospira biology will present opportunities to develop methods to address this pathogen, and will also serve as a model to understand the basic biology and pathogenic potential of emerging pathogenic species.