Identification of Francisella tularensis extracellular proteins expressed in vivo

描述(申请人提供)：本研究方案的目标是鉴定图拉氏方济氏菌S4的毒力因子。在自然界中，图拉氏丝虫引起人畜共患疾病图拉热症。图拉氏丝虫是一种A类选择药物，因为它具有高度传染性，而且可能容易通过气雾化传播。世界范围内的恐怖主义活动导致人们越来越担心图拉氏丝虫可能被用作生物恐怖武器；作为回应，美国国家过敏和传染病研究所扩大了其生物防御研究计划，以努力开发新的图拉氏丝虫疗法和疫苗。这项拟议研究的长期目标是为治疗图拉热症的治疗方法的发展确定新的目标。我们将使用遗传方法来鉴定在宿主细胞生长过程中特异表达的图拉氏F菌基因。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。在特定目的2中，将筛选基因组文库中体内表达的基因，并在特定目的中，将在动物模型中测试体内表达基因中的3个零突变。这项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大量线索。公共卫生相关性：这项研究项目的重点是确定图拉氏方济氏菌引起图拉热症的机制。

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.