Rickettsia conorii O antigen is the target of bactericidal Weil-Felix antibodies

Genetic analysis of Rickettsia has been difficult. We developed a transposon and selection scheme to facilitate the isolation of Rickettsia conorii mutants with insertional lesions. Here, we demonstrate that the R. conorii polysaccharide synthesis operon (pso) encompasses genetic determinants for biosynthesis of the O antigen, which also affect the composition of outer-membrane proteins, invasion of host cells, and pathogenesis. The O antigen provides essential barrier functions and plays a major role in host-pathogen interactions. Our findings suggest that infected hosts develop protective immunity against R. conorii via the production of antibodies targeting the O antigen. Conservation of pso among rickettsial species suggests that it may play a universal role in O-antigen synthesis, disease pathogenesis, and the development of immunity.