Identification of Francisella tularensis extracellular proteins expressed in vivo

描述（由申请方提供）：本研究提案的目标是鉴定土拉热弗朗西斯菌Schu S4的毒力因子。在自然界中，F.土拉热引起人畜共患病土拉菌病。F.土拉热是A类选择性病原体，因为它具有高度传染性，并且可能易于通过雾化传播。世界范围内的恐怖活动导致人们越来越关注F的潜在用途。作为回应，国家过敏和传染病研究所扩大了其生物防御研究计划，努力开发新的F。土拉热病治疗剂和疫苗。拟议研究的长期目标是确定新的靶点，用于开发治疗土拉菌病的疗法。我们将使用遗传学方法来鉴定F。土拉热菌基因在宿主细胞生长期间特异性表达。根据我们的研究目标，提出了三个科学目标。在具体目标1中，将构建基因组文库。在具体目标2中，将筛选基因组文库中的体内表达基因，并且在具体目标3中，将在兔热病动物模型中测试体内表达基因中的无效突变体。拟议工作的结果将为药物发现，细胞生物学实验和微生物学实验提供许多线索。公共卫生相关性：该研究项目的重点是确定土拉热弗朗西斯菌引起土拉菌病的机制。

DESCRIPTION (provided by applicant): The goal of this research proposal is to identify virulence factors in Francisella tularensis Schu S4. In nature, F. tularensis causes the zoonotic disease tularemia. F. tularensis is a category A select agent because of its highly infectious nature and the potential ease of its dissemination by aerosolization. Worldwide terrorist activities have resulted in growing concerns about the potential use of F. tularensis as a bioterrorist weapon; in response, the National Institute of Allergy and Infectious Diseases has expanded its biodefense research program in an effort to develop new F. tularensis therapeutics and vaccines. The long-term goal of the proposed research is to identify novel targets for the development of therapeutics for the treatment of tularemia. We will use a genetic approach to identify F. tularensis genes that are specifically expressed during growth in host cells. In accordance with our research goals, three scientific aims are proposed. In specific aim 1 a genomic library will be constructed. In specific aim 2 the genomic library will be screened for in vivo expressed genes and in specific aim 3 null mutants in in vivo expressed genes will be tested in an animal model of tularemia. The results of the proposed work will provide numerous leads for drug discovery, cell biology experiments, and microbiological experiments. PUBLIC HEALTH RELEVANCE: This research project is focused on defining the mechanism by which Francisella tularensis causes the disease tularemia.