Francisella tularensis purine auxotrophs as vaccines candidates

土拉热弗朗西丝菌是一种兼性胞内型人畜共患病病原体，是土拉菌病的病原体。它 具有1-10个生物体之间的感染剂量，并且能够引起急性衰弱疾病， 高死亡率的人类。F. tularensis已被指定为A类选择代理，因为它是一个 生物战的潜在代理人目前对这种病毒所利用的毒力决定因素知之甚少。 在宿主中引起疾病的微生物。此外，没有许可的疫苗可用于发生 故意释放这种细菌。对F.土拉热 宿主将大大提高我们对这种生物体所利用的机制的理解， 疾病，并促进能够提供保护性免疫的新型疫苗株的构建。在 这个新的机会应用程序，一个未标记的purMCD缺失突变体将产生在A型 菌株F.土拉热菌，并分析其作为活减毒疫苗候选物和宿主的能力 用于基于体内表达技术（IVET）毒力基因鉴定菌株。总的来说，这些 这些研究有望为F.土拉热症 主持人重要的是，本申请中提出的实验将提供先进的概念验证， 嘌呤营养缺陷型作为F.土拉热。

Francisella tularensis is a facultative intracellular zoonotic pathogen and the etiological agent of tularemia. It has an infectious dose of between 1-10 organisms, and is capable of causing an acute debilitating disease in humans with high mortality rates. F. tularensis has been designated a Category A Select Agent as it is a potential agent of biowarfare. Little is currently known about the virulence determinants utilized by this organism to cause disease in the host. In addition, there is no licensed vaccine available in the event of an intentional release of this bacterium. Identification of genes contributing to virulence of F. tularensis within the host would greatly improve our understanding of the mechanisms utilized by this organism to cause disease, and facilitate the construction of novel vaccine strains capable of providing protective immunity. In this New Opportunities application, an unmarked purMCD deletion mutant will be generated in a type A strain of F. tularensis and analyzed for its ability to serve as a live attenuated vaccine candidate and host strain for in vivo expression technology (IVET)-based virulence gene identification. Collectively, these studies are expected to provide important insights into the genes required by F. tularensis for growth within the host. Importantly, experiments proposed in this application will provide advanced proof-of-concept of purine auxotrophs as viable live vaccine candidates for F. tularensis.