Borrelila burgdorferi interacts intimately with host cells. both by extracellular adherence and by direct uptake into the mammalian cell. The bacterial- and host-encoded factors that mediate these phenomena have yet to be identified. The long term objectives of this research are to identify strategies used by B. burgdorferi to promote adherence and entry into host cells, and to determine which bacterial- and host-encoded factors are required for these events. Preliminary studies indicate that a variety of molecular techniques can be used to approach these goals. To this end, the following experiments will be performed to initiate an analysis of B. burgdorferi-host cell interaction: 1) Adherence and entry into neural, endothelial, and synovial cultured cells will be characterized in detail. The relative affinity of the spirochete for each cell type and the effect of various states of cellular activation on these processes will be determined. 2) Molecular clones of B. burgdorferi that encode factors promoting adherence and entry into mammalian cells will be isolated. The clones will be subjected to a detailed genetic analysis, and investigated in regards to their potential tissue tropism. 3) The ability of the identified B. burgdorferi adherence factors to promote cellular penetration will be investigated using immunochemical and hybrid protein techniques. 4) Mammalian cell receptors for adhesion factors will be identified by the isolation of monoclonal antibodies that block B. burgdorferi-host cell interaction. Lyme disease is apparently the result of a persistent strategy infection by B. burgdorferi. Entry into host cells is a potential strategy for Borrelia burgdorferi to protect itself from immune clearance mechanisms and establish such a persistent state. An investigation of how the entry process occurs would allow a better understanding of the disease process initiated by this spirochete, as well as the development of new chemotherapies that block this step in the infection process.
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