Infection proteomics

人畜共患病病原体钩端螺旋体是钩端螺旋体病的病原体，钩端螺旋体病是一种具有全球重要性的疾病，通过接触传染性体液和组织，或通过直接接触被尿液污染的土壤或淡水而获得。钩端螺旋体是一种自由生活的螺旋体细菌属，包括环境和致病物种。致病性钩端螺旋体具有特别的科学价值，因为它们能够适应和生长在包括土壤和淡水在内的各种环境中。值得注意的是，这些生物还具有抵抗哺乳动物宿主防御系统的选择压力的遗传能力，并且可以在人和动物中获得高数量的钩端螺旋体。目前人们对促进钩端螺旋体适应这些不同环境的差异基因和蛋白质表达谱知之甚少。在本研究方案中，我们将比较哺乳动物宿主中钩端螺旋体的全球蛋白质表达谱。这些研究将通过全蛋白质组水平的分析提供对钩端螺旋体感染过程的洞察。本研究的总体目标是评估病原体在感染过程中的蛋白质表达谱；这些研究将构成感染过程中任何病原体的第一次全球蛋白质表达分析。从我们的模式病原体钩端螺旋体上进行的研究获得的信息将使未来能够对其他表现出不同感染能力的病原体进行研究。如果我们在整个蛋白质组规模上对感染过程的了解取得进展，将对微生物学、细菌发病机制、分子生物学和其他与感染和免疫有关的学科的各个领域做出重大贡献。此外，这些研究的进展将直接使加拿大受益，因为钩端螺旋体病和其他由病原体引起的疾病在加拿大各地都有发生。

The zoonotic pathogen Leptospira is the causative agent of leptospirosis, a disease of global importance that is acquired by exposure to infectious body fluids and tissues or by direct contact with urine-contaminated soil or fresh water.  Leptospira are a genus of free-living spirochetal bacteria, comprising both environmental and pathogenic species. The pathogenic Leptospira are of particular scientific interest due to their ability to adapt to and grow in a variety of environments, including soil and fresh water. Remarkably, the organisms also have the genetic capacity to resist the contrasting selective pressures of the mammalian host defense system and can attain high numbers in both humans and animals.  Little is currently known about the differential gene and protein expression profiles facilitating Leptospira adaptation to these various milieus.  In this research proposal, we will compare global protein expression profiles of leptospires in the mammalian host.  These studies will provide insight into the leptospiral infection process via analyses at the whole-proteome level.  The overall objective of this research is to assess the protein expression profile of a pathogen during infection; these investigations will constitute the first global protein expression analysis of any pathogen during the infection process.  Information gained from studies performed on our model pathogen, Leptospira, will allow future investigations on additional pathogens that exhibit diverse infection capabilities.  Advances in our understanding of the infection process at the whole proteome scale will significantly contribute to the varied fields of microbiology, bacterial pathogenesis, molecular biology and other disciplines relating to infection and immunity.  In addition, advances made in these studies will directly benefit Canada, since leptospirosis and other diseases caused by pathogenic organisms occur throughout the country.