Bacteriodes fragilis is the most commonly isolated anaerobic pathogen isolated from infections such as intraabdominal abscess formation and anaerobic bacteremia in humans. The complex capsular polysaccharide (CPC) of B. fragilis has been identified as the primary virulence factor for this organism. Studies have shown that this macromolecule mediates abscess formation in the infected host and induces a form of T-cell immunity that is unusual for bacterial polysaccharides. The CPC comprises a complex of two discrete, surface expressed polysaccharides, termed polysaccharides A and B. Each of these polymers possesses free amino and carboxyl or phosphate groups that serve, in part, to link these polysaccharides together by ionic interactions. Moreover, the charged substituent groups on the B.fragllis polysaccharides mediate the ability of these polymers to provoke abscess formation and confer protection against abscess induction in animal model of sepsis. These studies provide a structural rationale for the distinct biologic properties associated with the CPC and demonstrate that this encapsulation motif represents a novel type of capsular polysaccharide found in association with bacteria pathogenic for humans. Investigation of the T cell dependent properties associated with the B.fragilis polysaccharides demonstrated that each of the component polymers are mitogenic for T cells, a trait previously thought to be associated only with protein based antigens. The long term objective of this proposal is to elucidate the mechanism by which the B.fragilis polysaccharides induce the formation of a specific pathobiologic host response in humans---abscess induction.
Specific aims to achieve this goal include: 1) determination of polysaccharide A binding to T-cells and/or antigen presenting cells in vitro, 2) characterization of the nature of the polysaccharide A -T cell/antigen presenting cell interaction, and 3) immunologic assessment of the mitogenic properties associated with polysaccharide A. These studies will determine how this novel class of T cell mitogens interacts with the cell mediated immune system as prelude to T cell activation. This research will expand our understanding of how bacteria promote abscess formation in the peritoneal cavity and may lead to better therapeutic measures to prevent or treat this disease process.
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