Project summary: Lyme disease is the most common tick-borne disease in the northern hemisphere. The incidence of Lyme disease is steadily increasing as the Ixodes tick population expands. This proposal will identify the critical functional determinants of outer surface protein C (OspC), an essential virulence factor. In addition, we will determine how sequence variation in OspC influences infectivity and dissemination properties. Cutting edge genetic approaches will be employed to dissect the role that OspC plays in the pathobiology of the Lyme disease spirochetes. The outcome of these analyses will also advance ongoing efforts to develop vaccines and diagnostic antigens for use in humans.