Rickettsia parkeri Sca2 promotes dissemination in an intradermal infection mouse model

Arthropod-borne pathogens cause severe human and animal diseases worldwide; however, current animal models are often inadequate in recapitulating key features of infection. Here, we report an intradermal infection model for Rickettsia parkeri, which causes eschar-associated spotted fever rickettsiosis in humans. We show that infection of mice lacking both interferon receptors (Ifnar-/-Ifngr-/-) with R. parkeri causes skin lesion formation similar to human eschars and disseminated disease with as few as 10 bacteria. Using this model, we found that the actin-based motility protein Sca2 is dispensable for R. parkeri survival in organs but is required for R. parkeri dissemination from the skin to peripheral tissues and for causing lethal disease. We also found that immunizing mice with sca2 and ompB mutant R. parkeri protects against subsequent rechallenge with wild-type bacteria. This study characterizes a mouse model that mimics aspects of human rickettsial disease and reveals a pathogenic role for the R. parkeri actin-based motility protein Sca2 in dissemination.