Our research approach is to understand the virulence of Treponema pallidum, the causative agent of syphilis, by identifying, purifying and characterizing outer envelope proteins of the spirochete that possess important biological functions. Emphasis focuses on treponemal proteins that mediate surface parasitism of eucaryotic cells, probably through recognition of fibronectin or fibronectin-like macromolecules associated with host cell membranes. Chemical dissection of fibronectin will permit analysis of the specific binding region(s) or domain(s) for treponemal outer envelope ligands. This should lead to improved purification of the specific T. pallidum adhesin proteins. A combination of methodologies will be employed which include use of radiolabeling techniques, affinity chromatography, gel electrophoresis, aqueous and selected detergent extracts of treponemal components, radio-immunoassays and microELISA techniques, monoclonal and monospecific antibody reagents, autoradiography-fluorography and electron microscopy. Long term objectives are to define the virulence determinants of T. pallidum and the pathogenesis of syphilis by focusing on receptor-ligand mechanisms of recognition between host macromolecules and surface proteins of T. pallidum. Data presented in the Preliminary Studies and Appendix sections suggest tha these interactions may influence the disease process.
