title: Demonstration of factor H-like protein 1 binding to Treponema denticola, a pathogen associated with periodontal disease in humans.
abstract: Treponema denticola is an important contributor to periodontal disease. In this study we investigated the ability of T. denticola to bind the complement regulatory proteins factor H and factor H-like protein 1 (FHL-1). The binding of these proteins has been demonstrated to facilitate evasion of the alternative complement cascade and/or to play a role in adherence and invasion. Here we demonstrate that T. denticola specifically binds FHL-1 via a 14-kDa, surface-exposed protein that we designated FhbB. Consistent with its FHL-1 binding specificity, FhbB binds only to factor H recombinant fragments spanning short consensus repeats (SCRs) 1 to 7 (H7 construct) and not to SCR constructs spanning SCRs 8 to 15 and 16 to 20. Binding of H7 to FhbB was inhibited by heparin. The specific involvement of SCR 7 in the interaction was demonstrated using an H7 mutant (H7AB) in which specific charged residues in SCR 7 were replaced by alanine. This construct lost FhbB binding ability. Analyses of the ability of FHL-1 bound to the surface of T. denticola to serve as a cofactor for factor I-mediated cleavage of C3b revealed that C3b is cleaved in an FHL-1/factor I-independent manner, perhaps by an unidentified protease. Based on the data presented here, we hypothesize that the primary function of FHL-1 binding by T. denticola might be to facilitate adherence to FHL-1 present on anchorage-dependent cells and in the extracellular matrix.
authors.affiliation: Department of Microbiology and Immunology, P.O. Box 980678, Richmond, VA 23298-0678, USA.
authors.forename: John V
authors.initials: JV
authors.lastname: McDowell
authors.forename: Justin
authors.initials: J
authors.lastname: Lankford
authors.forename: Lola
authors.initials: L
authors.lastname: Stamm
authors.forename: Tania
authors.initials: T
authors.lastname: Sadlon
authors.forename: David L
authors.initials: DL
authors.lastname: Gordon
authors.forename: Richard T
authors.initials: RT
authors.lastname: Marconi
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D018441:Biofilms; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism*; D003179:Complement C3b / Q000502:physiology; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000737:chemistry*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D010510:Periodontal Diseases / Q000382:microbiology*; D011485:Protein Binding; D048373:Treponema denticola / Q000378:metabolism*; D014211:Treponemal Infections / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D001798:Blood Proteins; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D003179:Complement C3b; D017242:Complement Factor H; D006493:Heparin