title: Sequence divergence in the Treponema denticola FhbB protein and its impact on factor H binding.
abstract: Treponema denticola is an anaerobic spirochete whose abundance in the subgingival crevice correlates with the development and severity of periodontal disease. The ability of T. denticola to survive and thrive in the hostile environment of the periodontal pocket is due, at least in part, to its ability to bind factor H (FH), a negative regulator of the alternative complement pathway. The FH binding protein of T. denticola has been identified as FhbB and its atomic structure has been determined. The interaction of FH with T. denticola is unique in that FH bound to the cell surface is cleaved by the T. denticola protease, dentilisin. It has been postulated that FH cleavage by T. denticola leads to immune dysregulation in periodontal pockets. In this study, we conduct a comparative assessment of the sequence, properties, structure and ligand binding kinetics of the FhbB proteins of strains 33521 and 35405. The biological outcome of the interaction of these strains with FH could differ significantly as 33521 lacks dentilisin activity. The data presented here offer insight into our understanding of the interactions of T. denticola with the host and its potential to influence disease progression.
authors.affiliation: Department of Microbiology and Immunology, Medical College of Virginia at Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Miller
authors.forename: J V
authors.initials: JV
authors.lastname: McDowell
authors.forename: D V
authors.initials: DV
authors.lastname: Rhodes
authors.forename: A
authors.initials: A
authors.lastname: Allard
authors.forename: M
authors.initials: M
authors.lastname: Caimano
authors.forename: J K
authors.initials: JK
authors.lastname: Bell
authors.forename: R T
authors.initials: RT
authors.lastname: Marconi
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000032:analysis / Q000235:genetics*; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics*; D001483:Base Sequence / Q000235:genetics; D002918:Chymotrypsin / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D019295:Computational Biology; D017124:Conserved Sequence / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007155:Immunologic Factors / Q000276:immunology; D008024:Ligands; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D016297:Mutagenesis, Site-Directed; D010447:Peptide Hydrolases; D010514:Periodontal Pocket / Q000276:immunology / Q000382:microbiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D048373:Treponema denticola / Q000201:enzymology* / Q000235:genetics / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007106:Immune Sera; D007155:Immunologic Factors; D008024:Ligands; D017242:Complement Factor H; D010447:Peptide Hydrolases; C102570:dentilisin; D002918:Chymotrypsin
keywords: complement; factor H; immune evasion; periodontitis