Tight regulation of surface antigenic expression is crucial for the pathogenic strategy of the Lyme disease spirochete, Borrelia burgdorferi. Here, we report the influence of increasing expression of
decorin-
binding protein A (
DbpA), one of the most investigated spirochetal surface adhesins, on the 50% infectious dose (ID(50)), dissemination, tissue colonization, pathogenicity, and persistence of B. burgdorferi in the murine host. Our in vitro assays showed that increasing
DbpA expression dramatically increased the interaction of B. burgdorferi with
decorin and sensitivity to growth inhibition/killing by anti-
DbpA antibodies; however, this increased interaction did not affect spirochetal growth and replication in the presence of
decorin. Increasing
DbpA expression significantly reduced ID(50) values and severely impaired dissemination in
severe combined immunodeficiency (SCID) and immunocompetent mice. During
infection of SCID mice, B. burgdorferi with increased
DbpA expression was able to effectively colonize heart and skin tissues, but not joint tissues, completely abrogating
arthritis virulence. Although increasing
DbpA expression did not affect spirochetal persistence in the skin, it diminished the ability of B. burgdorferi to persist in the heart and joint tissues during
chronic infection of immunocompetent mice. Taken together, the study highlights the importance of controlling
surface antigen expression in the infectivity, dissemination, tissue colonization, pathogenicity, and persistence of B. burgdorferi during mammalian
infection.