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Infection and Immunity, November 2005, p. 7126-7132, Vol. 73, No. 11
0019-9567/05/$08.00+0 doi:10.1128/IAI.73.11.7126-7132.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Demonstration of Factor H-Like Protein 1 Binding to Treponema denticola, a Pathogen Associated with Periodontal Disease in Humans
John V. McDowell,1
Justin Lankford,1
Lola Stamm,3
Tania Sadlon,4
David L. Gordon,4 and
Richard T. Marconi1,2*
Department of Microbiology and Immunology,1
Center for the Study of Biological Complexity, Medical College of Virginia at Virginia Commonwealth University, Richmond, Virginia 23298-0678,2
Department of Epidemiology, Infectious Diseases Program, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,3
Department of Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, South Australia, Australia4
Received 16 June 2005/
Returned for modification 29 July 2005/
Accepted 5 August 2005
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.
* Corresponding author. Mailing address: Department of Microbiology and Immunology, P.O. Box 980678, Richmond, VA 23298-0678. Phone: (804) 828-3779. Fax: (804) 828-9946. E-mail:
rmarconi{at}hsc.vcu.edu.
Editor: D. L. Burns
Infection and Immunity, November 2005, p. 7126-7132, Vol. 73, No. 11
0019-9567/05/$08.00+0 doi:10.1128/IAI.73.11.7126-7132.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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