<i>Rickettsia conorii</i> O antigen is the target of bactericidal Weil-Felix antibodies.

Abstract

Rickettsial diseases have long been diagnosed with serum antibodies cross-reactive against <i>Proteus vulgaris</i> (Weil-Felix reaction). Although Weil-Felix antibodies are associated with the development of immunity, their rickettsial target and contribution to disease pathogenesis are not established. Here, we developed a transposon for insertional mutagenesis of <i>Rickettsia conorii</i>, isolating variants defective for replication in cultured cells and in spotted fever pathogenesis. Mutations in the <i>polysaccharide synthesis operon</i> (<i>pso</i>) abolish lipopolysaccharide O-antigen synthesis and Weil-Felix serology and alter outer-membrane protein assembly. Unlike wild-type <i>R. conorii</i>, <i>pso</i> mutants cannot elicit bactericidal antibodies that bind O antigen. The <i>pso</i> operon is conserved among rickettsial pathogens, suggesting that bactericidal antibodies targeting O antigen may generate universal immunity that could be exploited to develop vaccines against rickettsial diseases.