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Infection and Immunity, April 2009, p. 1417-1425, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01544-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Analysis of a Unique Interaction between the Complement Regulatory Protein Factor H and the Periodontal Pathogen Treponema denticola{triangledown}

John V. McDowell,1 Bernice Huang,1 J. Christopher Fenno,3 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 Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan3

Received 19 December 2008/ Returned for modification 20 January 2009/ Accepted 2 February 2009

Treponema denticola, a spirochete associated with periodontitis, is abundant at the leading edge of subgingival plaque, where it interacts with gingival epithelia. T. denticola produces a number of virulence factors, including dentilisin, a protease which is cytopathic to host cells, and FhbB, a unique T. denticola lipoprotein that binds complement regulatory proteins. Earlier analyses suggested that FhbB specifically bound to factor H (FH)-like protein 1 (FHL-1). However, by using dentilisin-deficient mutants of T. denticola, we found that T. denticola preferentially binds FH and not FHL-1, and that FH is then cleaved by dentilisin to yield an FH subfragment of ~50 kDa. FH bound to dentilisin-deficient mutants but was not cleaved and retained its ability to serve as a cofactor for factor I in the cleavage of C3b. To assess the molecular basis of the interaction of FhbB with FH, mutational analyses were conducted. Replacement of specific residues in widely separated domains of FhbB and disruption of a central alpha helix with coiled-coil formation probability attenuated or eliminated FH binding. The data presented here are the first to demonstrate the retention at the cell surface of a proteolytic cleavage product of FH. The precise role of this FH fragment in the host-pathogen interaction remains to be determined.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, P.O. Box 980678, Virginia Commonwealth University, Richmond, VA 23298-0678. Phone: (804) 828-3779. Fax: (804) 828-9946. E-mail: rmarconi{at}vcu.edu

{triangledown} Published ahead of print on 9 February 2009.

Editor: J. B. Bliska

Infection and Immunity, April 2009, p. 1417-1425, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01544-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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