IAI Accepts, published online ahead of print on 9 February 2009

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Infect. Immun. doi:10.1128/IAI.01544-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Analysis of a unique interaction between the complement regulatory protein factor H and the periodontal pathogen Treponema denticola

John V. McDowell, Bernice Huang, J. Christopher Fenno, and Richard T. Marconi^*

Department of Microbiology and Immunology, Center for the Study of Biological Complexity, Medical College of Virginia at Virginia Commonwealth University, Richmond, VA 23298-0678; and Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan

^* To whom correspondence should be addressed. Email: rmarconi{at}vcu.edu.

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 like protein 1 (FHL-1). However, using dentilisin deficient mutants of T. denticola, here we describe that T. denticola preferentially binds Factor H (FH) and not FHL-1, and that the FH is then cleaved by dentilisin, to yield a FH sub-fragment of 50 kDa. FH bound to dentilisin deficient mutants but was not cleaved and retained its ability to serve as a co-factor for Factor I in the cleavage of C3b. To assess the molecular basis of the interaction of FhbB with FH, mutational analyses were conducted. Substitution 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 within are the first to demonstrate retention at the cell surface of a proteolytic cleavage product of FH. The precise role for this FH fragment in the host-pathogen interaction remains to be determined.