Periodontal disease is the major cause of tooth loss in adults and is the second most common infection in man after dental caries. The gram-negative bacillus, Bacteroides gingivalis, is a predominant isolate from advancing lesions of adult periodontitis and an increase in serum antibody levels specfic for Bacteroides gingivalis is consistently observed in adult periodontitis. These findings coupled with the infrequent occurrence of the organism, and low levels of antibody found in normal individuals, and the virulence factors produced by B. gingivalis provide evidence for its etiologic role in adult periodontitis. The purification and characterization of the capsular polysaccharide antigen of Bacteroides gingivalis should provide us with new insight into the pathogenesis of periodontal infection with Bacteroides gingivalis. The purification of the capsular polysaccharide antigen and its role in the pathogenecity of Bacteroides gingivalis will be the objective of this research plan which is composed of two phases. Phase I will involve the purification of the capsular polysaccharide from Bacteroides gingivalis and its chemical, structural, and immunochemical characterization. A radioactive antigen-binding assay for the measurement of anticapsular antibodies to Bacteroides gingivalis will be developed. The antigen will be purified from large-scale growth of bacteria by enzymatic and chromatographic methods. Routine chemical analysis will define its chemical composition. Structural analysis will be obtained by methylation analysis of the polysaccharide and modified derivatives by gas chromatography-mass spectroscopy. Immunochemical characterization will be by gel diffusion, crossed immunoelectrophoresis, quantitative precipitation studies, and radioactive antigen-binding assays. Phase II will evaluate the efficacy of immunization with the capsular polysaccharide toward the prevention of bacteremia and toward abscess formation in rodent models of infection. The ability of the capsular polysaccharide to modify the adherence of B. gingivalis to buccal epithelial cells and to selected gram-positive bacteria will be evaluated in attempts to understand the role of the capsule in adherence. Its ability to affect the phagocytosis of B. gingivalis by neutrophils will be examined in experiments designed to assess the potential virulence role of the capsular polysaccharide. The level of anticapsular antibody in serum, saliva, and gingival crevicular fluid will be measured and correlated to disease status in patients with adult periodontitis enrolled in a longitudinal study. Thus, Phase II will evaluate the biological effects and the host response elicited by the capsular polysaccharide.
| Wilson, M E; Schifferle, R E (1991) Evidence that the serotype b antigenic determinant of Actinobacillus actinomycetemcomitans Y4 resides in the polysaccharide moiety of lipopolysaccharide. Infect Immun 59:1544-51 |
| Schifferle, R E; Reddy, M S; Zambon, J J et al. (1989) Characterization of a polysaccharide antigen from Bacteroides gingivalis. J Immunol 143:3035-42 |
