This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The gram-negative coccobacillus Francisella tularensis is the causative agent of tularemia. The natural reservoir includes small mammals such as ground squirrels, hares, voles, muskrats, water rats, rabbits and other rodents. This illness is spread to humans from infected reservoirs and other small vertebrates through direct contact or transmission from an arthropod vector. Tularemia is manifested in various ways including ulcers at the site of inoculation, pharyngitis, lymphadenopathy, and pneumonia. Immediate treatment with appropriate antibiotics can reduce the possibility of life-threatening pneumonia. F. tularensis is a category A agent. The infectious dose for this agent by inhalation is reported to be as few as 10 organisms. Much less information is known about the mortality of GI tularemia. The ultimate goal for this project is to characterize pathogenesis of disease in nonhuman primates and to assess effectiveness of fluoroquinolone treatment in protecting against lethal disease.