Francisella tularensis purine auxotrophs as vaccines candidates

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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.