Increasing the Interaction of Borrelia burgdorferi with Decorin Significantly Reduces the 50 Percent Infectious Dose and Severely Impairs Dissemination

摘要

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 (ID50), 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 ID50 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.