Murine Lyme arthritis results from Borrelia burgdorferi colonization of joints and the ensuing host response. In a mammalian host, B. burgdorferi persists in a wide range of tissues and we hypothesize that spirochetes induced selected genes - in precise host location and in time - and that these gene products are critical for the spirochete persistence and genesis of the disease, such as Lyme arthritis. Using microarray-based differential analysis of B. burgdorferi gene expression in murine tissues, and quantitative RT-PCR, we have now identified a spirochete gene, bmpA, which is preferentially upregulated in murine joints compared to other tissues. Interestingly, transfer of BmpA-specific antibodies into B. burgdorferi-infected mice selectively reduced spirochete numbers and inflammation in the joints. The goals of this proposal are, therefore, to generate B. burgdorferi lacking bmpA and further explore the role of this joint-induced protein in the pathogenesis of Lyme arthritis. We will assess if bmpA mutant B. burgdorferi will be infectious in mice but unable to effectively persist in joints. Also, we will determine if the bmpA mutant fails to induce arthritis and whether complementation of the mutant B. burgdorferi with the bmpA gene will restore the original phenotype. As BmpA is highly induced in infected joints, we will determine if this specific spirochete protein plays a greater role in triggering the host inflammatory response. We will measure alteration of selected host immunomodulatory factors in mice infected with wild type or bmpA mutants. These data will delineate the critical role of the differentially produced B. burgdorferi antigens in the spirochete infection of joints. Furthermore, our may lead to the new strategies for the treatment of Lyme arthritis.
