FIBRINOGEN BINDING AND VIRULENCE OF BACTEROIDES SPECIES

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Some forms of gingivitis and periodontitis are associated with proportional increases (emergence) of indigenous black-pigmented Bacteroides species in the subgingival microbiota, particularly Bacteroides gingivalis and Bacteroides intermedius. It is not known what virulence factor or factors permit emergence of these organisms, or whether emergence of these organisms contributes to the pathogenesis of gingivitis and periodontitis. A number of B. gingivalis and B. intermedius strains bind and adhere to fibrinogen and fibrin in vitro. Binding and adherence of these strains to fibrinogen are mediated by a bacterial protein (Mr 200k). Studies are proposed to investigate whether fibrinogen binding protein (FBP) is an in vivo virulence factor necessary for emergence of B. gingivalis in developing periodontitis lesions in the cynomolgus monkey. Elucidation of mechanisms of emergence of Bacteroides species is important in understanding their etiologic role in periodontal diseases. An understanding of these mechanisms is also necessary to achieve the long range goal of this research which is to develop strategies to block emergence of these organisms and thereby block the development of periodontitis. The following Specific Aims are proposed: 1. To purify fibrinogen binding proteins from human and cynomolgus strains of Bacteroides gingivalis and Bacteroides intermedius. 2. To characterize and compare fibrinogen binding proteins from monkey and human strains of Bacteroides gingivalis and Bacteroides intermedius. 3. To determine if Bacteroides gingivalis fibrinogen binding protein is an in vivo virulence factor in the cynomolgus monkey model of ligature-induced periodontitis by: (1) determining if active immunity to B. gingivalis FBP (a) prevents emergence of B. gingivalis or other Bacteroides species in the microbiota of developing periodontitis lesions, or (b) prevents development of periodontitis and (2) determining if B. gingivalis mutants lacking fibrinogen binding protein (FBP-) can implant and emerge in the microbiota of developing periodontitis lesions.