Demonstration of factor H-like protein 1 binding to Treponema denticola, a pathogen associated with periodontal disease in humans.
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.
McDowell
John V
JV
Department of Microbiology and Immunology, P.O. Box 980678, Richmond, VA 23298-0678, USA.
Lankford
Justin
J
Stamm
Lola
L
Sadlon
Tania
T
Gordon
David L
DL
Marconi
Richard T
RT
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*
D001426:Bacterial Proteins; D001798:Blood Proteins; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D003179:Complement C3b; D017242:Complement Factor H; D006493:Heparin