Examination of Borrelia burgdorferi OspC as an adhesin and at the host-pathogen interface

Borrelia burgdorferi is a tick-transmitted spirochete that causes Lyme disease. As an extracellular bacterium it employs adhesion mechanisms that are postulated to help the bacteria disseminate throughout the host and establish a persistent infection. Using various in vitro methods, a number of different molecules on the surface of host cells have been identified previously as receptors to which Borrelia burgdorferi binds.;Using a novel approach, a filamentous phage display selection in vivo, a number of Borrelia burgdorferi proteins have been identified as candidate adhesins, among them the members of the OspF family and OspC. We examined their roles as candidate adhesins and began work toward identification of their respective receptors. The members of the OspF family are part of the larger family of the Erp proteins; some Erp members have been previously identified as adhesins. It has been shown that OspC is required for the establishment of an infection in mammals even in the absence of an adaptive immune response. We hypothesized that it may play a role in the modulation of the innate immune response of the host to promote the successful establishment of infection.;We showed that ErpK, a representative of the OspF family, is a candidate adhesin that binds to a receptor located on the surface of the epithelial cell line A459. In addition, we found that OspC is a candidate adhesin of Borrelia burgdorferi, and that its potential receptor belongs to the glycosaminoglycan family. We have also found that OspC does not alter the host's innate immune response, as the same cytokines are produced at similar levels at the site of the infection in the skin, and by infection of macrophages in vitro, in response to infection by wild-type and OspC-deficient Borrelia burgdorferi. Nonetheless, its presence is important for the survival of the bacteria in vivo. This suggests that OspC may play a role in helping the bacteria sense and adapt to the new environment inside the mammalian host. A wide array of cytokines was tested and it was shown for the first time that MCP-1 and KC are produced in the skin of mice at the site of the infection. Additionally, we report for the first time that VEGF is being produced in the skin of mice due to a Borrelia burgdorferi infection. VEGF induces the permeability of blood vessels so its secretion may be advantageous for the growth of the bacteria due to the availability of more nutrients in the area. Also, it may help them jump into circulation faster in order to disseminate to other parts of the body.