The Treponema denticola FhbB protein contributes to immune evasion by binding factor H (FH). Cleavage of FH by the T. denticola protease, dentilisin, may contribute to the local immune dysregulation that is characteristic of periodontal disease (PD). Although three FhbB phyletic types have been defined (FhbB1, FhbB2, and FhbB3), the in vivo expression patterns and antigenic heterogeneity of FhbB have not been assessed. Here, we demonstrate that FhbB is a dominant early antigen that elicits FhbB type-specific antibody (Ab) responses. Using the murine skin abscess model, we demonstrate that the presence or absence of FhbB or dentilisin significantly influences Ab responses to infection and skin abscess formation. Competitive binding analyses revealed that ␣-FhbB Ab can compete with FH for binding to T. denticola and block dentilisin-mediated FH cleavage. Lastly, we demonstrate that dentilisin cleavage sites reside within critical functional domains of FH, including the complement regulatory domain formed by CCPs 1 to 4. Analysis of the FH cleavage products revealed that they lack cofactor activity. The data presented here provide insight into the in vivo significance of dentilisin, FhbB and its antigenic diversity, and the potential impact of FH cleavage on the regulation of complement activation. P eriodontal disease (PD) of infectious etiology is a significant human and veterinary health concern. PD is a chronic inflammatory disease that degrades tissue and reabsorbs bone that surrounds and supports teeth, leading to endentulism (1). PD results from a dysbiosis of the polymicrobial community of the subgingival crevice. The transition of the bacterial population from predominantly Gram-positive organisms to destructive anaerobic spirochetes and Gram-negative organisms (2-4) is accompanied by local dysregulation of immunoregulatory mechanisms (5-8). Specific periopathogens, including Treponema denticola and Porphyromonas gingivalis, are thought to play leading roles in this process (8)(9)(10). This study is focused on T. denticola, an anaerobic, proteolytic (tissue degrading) spirochete of humans that is a dominant periopathogen and member of the "red microbial complex" (4, 11). T. denticola and other oral treponemes are also key players in root canal and endodontic infections (12, 13).Periopathogens thrive in the subgingival crevice, an anatomical niche bathed in gingival crevicular fluid (GCF). GCF is derived from serum and local tissue exudate (14) and is rich in immune effectors, including activated complement, C-reactive protein, opsonins (C3b and iC3b), anaphylatoxins, and proinflammatory cytokines (reviewed in references 1 and 15). T. denticola evades complement mediated destruction by binding factor H (FH), a negative regulator of the complement system (9, 16-18). FH, an abundant 150-kDa serum glycoprotein (ϳ300 g ml of serum Ϫ1 ) (19,20), consists of 20 imperfect repeat domains (CCPs) of 50 to 60 amino acids each that comprise different functional domains (21-25).The FH binding protein of T. denticola, Fh...

AMIX is effective in vitro in inhibiting growth and other processes central to virulence. AMIX could serve could serve as a new selective therapeutic tool for the treatment of periodontal disease.

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