a francisella tularensis schu s4 purine auxotroph is highly attenuated in mice but offers limited protection against homologous intranasal challenge一个土拉杆菌内schu s4嘌呤营养缺陷型高度减毒老鼠但提供有限的保护同源鼻内的挑战.pdfVIP

A Francisella tularensis Schu S4 Purine Auxotroph Is Highly Attenuated in Mice but Offers Limited Protection against Homologous Intranasal Challenge 1 1 3 3 1 Roger D. Pechous , Travis R. McCarthy , Nrusingh P. Mohapatra , Shilpa Soni , Renee M. Penoske , 1,2 1 3 1 Nita H. Salzman , Dara W. Frank , John S. Gunn , Thomas C. Zahrt * 1 Department of Microbiology and Molecular Genetics and Center for Biopreparedness and Infectious Diseases, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America, 2 Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America, 3 Center for Microbial Interface Biology, Department of Molecular Biology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, United States of America Abstract Background: Francisella tularensis is a Gram-negative coccobacillus that causes the febrile illness tularemia. Subspecies that are pathogenic for humans include those comprising the type A (subspecies tularensis) or type B (subspecies holarctica) biovars. An attenuated live vaccine strain (LVS) developed from a type B isolate has previously been used to vaccinate at-risk individuals, but offers limited protection against high dose (.1000 CFUs) challenge with type A strains delivered by the respiratory route. Due to differences between type A and type B F. tularensis strains at the genetic level, it has been speculated that utilization of an attenuated type A strain as a live vaccine might offer better protection against homologous respiratory challenge compared with LVS. Here, we report the construction