B GINGIVALIS POLYSACCHARIDES--STRUCTURE AND FUNCTION

细菌包封常与疾病有关

Bacterial encapsulation is frequently correlated with an enhancement of virulence. Encapsulated strains of Escherichia coli, Neisseria meningitidis, and Haemophilus influenzae demonstrate enhanced invasive properties and cause serious disease, while their unencapsulated counterparts are generally much less virulent. In the USA, capsular polysaccharide vaccines are commercially available for the prevention of disease by Ii. influenza type b, Streptococcus pneumoniae, and other encapsulated bacteria. Bacteroides gingivalis is an anaerobic gram-negative bacteria associated with periodontal disease. Previous studies have demonstrated the presence of a capsule on B. gingivalis and have attributed antiphagocytic properties to this capsule. This proposal will study the ability of this polysaccharide to contribute to this microorganism's virulence and the ability of this polysaccharide to function as an immunogen and induce the formation of protective antibodies, thus resulting in protection from infection with this bacteria. This proposal seeks to characterize the polysaccharides from different strains of B_. gingivalis, to use these polysaccharides as immunogens, and to study their biological effects. Polysaccharides will be isolated from different strains and chemically and immunochemically characterized. The immunogenicity of these polysaccharide will then be assessed by using: modified polysaccharide derivatives, polysaccharide-protein conjugate vaccines, different immunological adjuvants, and agents that can either stimulate or suppress different T cell populations which are involved in the immune response to polysaccharide antigens. The ability of these polysaccharide immunogens to modify the development of infection in an experimental mouse virulence model will then be investigated. The interaction of the polysaccharide with the serum complement system and its effect on phagocytosis by neutrophils will be determined. Finally, unencapsulated strains of B. gingivalis will be derived either by natural selection or through transposon mutagenesis and the virulence properties of these unencapsulated strains will be compared with the encapsulated bacteria. The results of these studies should greatly enhance our knowledge of the immunogenicity of bacterial polysaccharide antigens and to the contribution of the capsule to the virulence observed for B. gingivalis.