Analysis of a unique interaction between the complement regulatory protein factor H and the periodontal pathogen Treponema denticola.
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 approximately 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.
McDowell
John V
JV
Department of Microbiology and Immunology, Medical College of Virginia at Virginia Commonwealth University, Richmond, VA 23298-0678, USA.
Huang
Bernice
B
Fenno
J Christopher
JC
Marconi
Richard T
RT
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002918:Chymotrypsin / Q000378:metabolism; D017242:Complement Factor H / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010447:Peptide Hydrolases; D010510:Periodontal Diseases / Q000382:microbiology; D017422:Sequence Analysis, DNA; D048373:Treponema denticola / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014211:Treponemal Infections; D037521:Virulence Factors
D001426:Bacterial Proteins; D008074:Lipoproteins; D037521:Virulence Factors; D017242:Complement Factor H; D010447:Peptide Hydrolases; C102570:dentilisin; D002918:Chymotrypsin