Francisella Infection in Ticks

描述（由申请方提供）：土拉热弗朗西斯菌是土拉菌病的病原体，土拉菌病是一种通过啮齿动物、兔形动物及其体外寄生虫在环境中维持的人畜共患疾病。低感染剂量、与肺炎相关的高死亡率和基因工程F。土拉热促使人们更加努力地鉴定治疗剂或疫苗的关键靶点。新的遗传方法和工具已被开发为弗朗西斯菌，允许在理解组织培养和动物模型系统中感染期间发生的一些生物学结果方面取得快速进展。本申请提出开发弗朗西斯氏菌感染的第一个蜱-小鼠模型，并研究传播、组织定位和确定蜱发育不同阶段期间细菌负荷的变化。两个实验室的技能集中在这些主要目标上。Coburn博士带来了她在分析蜱传疏螺旋体感染方面的经验，Frank博士贡献了她在A型和B F型的遗传学和发病机制方面的专业知识。tularensis项目。蜱传F.土拉热是人类传播的主要方式，但对这些节肢动物载体中细菌的获取、维持或复制知之甚少。为了解决这一关键的知识差距，我们将建立第一个定义良好的蜱鼠感染模型系统使用非选择剂F。土拉热菌菌株LVS.总的来说，我们建议填补我们对tick/F的理解中的一个重要空白。tularensis生物学，并为未来的工作铺平了道路，使用遗传方法来确定介导蜱虫维持和传播到哺乳动物宿主的细菌的重要组成部分。这些细菌成分可以作为治疗或疫苗干预的新靶点。

DESCRIPTION (provided by applicant): Francisella tularensis is the etiologic agent of tularemia, a zoonotic disease maintained in the environment by rodents, lagamorphs and their ectoparasites. The low infectious dose, the high mortality rate associated with pneumonic disease and the potential to genetically engineer F. tularensis have prompted increased efforts to identify critical targets for therapeutics or vaccines. New genetic approaches and tools have been developed for Francisella, allowing rapid progress in understanding some of the biological outcomes occurring during infections both in tissue culture and in animal model systems. This application proposes to develop the first tick-mouse model of Francisella infection and to study transmission, tissue localization and define the changes in bacterial burden during different stages of tick development. The skill sets of two laboratories are focused on these major goals. Dr. Coburn brings her experience in the analysis of tick-borne Borrelia infections and Dr. Frank contributes her expertise in the genetics and pathogenesis of types A and B F. tularensis to the project. Tick-borne F. tularensis is a major mode of transmission to humans, yet little is known about the acquisition, maintenance or replication of the bacteria in these arthropod vectors. To address this critical knowledge gap, we will establish the first well-defined tick-mouse infection model system using the non-select agent F. tularensis strain LVS. Overall, we propose to fill an important gap in our understanding of tick/F. tularensis biology and pave the way for future work using genetic approaches to identify important components of the bacterium that mediate maintenance in the tick and transmission to mammalian hosts. These bacterial components may serve as novel targets for therapeutic or vaccine interventions.