This project examines mechanisms of pathogenesis of obligately intracellular bacteria. Studies on Coxiella burnetii, the etiologic agent of Q fever, have continued to focus on the lipopolysaccharides (LPS). Our demonstration last year of structural and/or antigenic variation in the LPS of strains of C. burnetii isolated from chronic Q fever endocarditis vs. acute Q fever has led us to analyze the role of LPS in pathogenesis. Studies in animal model systems have demonstrated that the LPS is a major determinant of virulence affecting both the fever response and ability of the microorganism to persist in the host. Comparisons of the virulence of endocarditis vs. acute type strains of C. burnetii have shown that both are extremely infectious, although the acute type strain has over 100,000-fold greater ability to induce a fever response. Structural analyses have revealed that the wild type LPS sterically blocks access of antibodies to the surface of C. burnetii. Surface proteins are accessible on the avirulent phase of C. burnetii. The role of serum complement in killing of avirulent C. burnetii has been demonstrated, thus providing an explanation for the avirulence of the phase II organisms. The two virulent phases 9mi/I and 9mi/Cr avoid complement killing by different mechanisms. Work with Chlamydia trachomatis has continued to focus on the putative adhesins. Affinity chromatography procedures for the purification of these molecules have been developed and purified proteins used to generate monoclonal antibodies. These antibodies will be used in attempts to molecularly clone the adhesins.
