title: Binding of complement inhibitor C4b-binding protein contributes to serum resistance of Porphyromonas gingivalis.
abstract: The periodontal pathogen Porphyromonas gingivalis is highly resistant to the bactericidal activity of human complement, which is present in the gingival crevicular fluid at 70% of serum concentration. All thirteen clinical and laboratory P. gingivalis strains tested were able to capture the human complement inhibitor C4b-binding protein (C4BP), which may contribute to their serum resistance. Accordingly, in serum deficient of C4BP, it was found that significantly more terminal complement component C9 was deposited on P. gingivalis. Moreover, using purified proteins and various isogenic mutants, we found that the cysteine protease high molecular weight arginine-gingipain A (HRgpA) is a crucial C4BP ligand on the bacterial surface. Binding of C4BP to P. gingivalis appears to be localized to two binding sites: on the complement control protein 1 domain and complement control protein 6 and 7 domains of the alpha-chains. Furthermore, the bacterial binding of C4BP was found to increase with time of culture and a particularly strong binding was observed for large aggregates of bacteria that formed during culture on solid blood agar medium. Taken together, gingipains appear to be a very significant virulence factor not only destroying complement due to proteolytic degradation as we have shown previously, but was also inhibiting complement activation due to their ability to bind the complement inhibitor C4BP.
authors.affiliation: Department of Laboratory Medicine, Section of Medical Protein Chemistry, University Hospital Malmö, Lund University, Malmö, Sweden.
authors.forename: Michal
authors.initials: M
authors.lastname: Potempa
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
authors.forename: Marcin
authors.initials: M
authors.lastname: Okroj
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Popadiak
authors.forename: Sigrun
authors.initials: S
authors.lastname: Eick
authors.forename: Ky-Anh
authors.initials: KA
authors.lastname: Nguyen
authors.forename: Kristian
authors.initials: K
authors.lastname: Riesbeck
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016866:Bacteroidaceae Infections / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D001770:Blood Bactericidal Activity / Q000235:genetics / Q000276:immunology*; D003167:Complement Activation / Q000235:genetics / Q000276:immunology; D050716:Complement C4b-Binding Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003186:Complement C9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D008024:Ligands; D009154:Mutation; D016966:Porphyromonas gingivalis / Q000201:enzymology / Q000276:immunology* / Q000472:pathogenicity; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017433:Protein Structure, Secondary / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D050716:Complement C4b-Binding Protein; D003186:Complement C9; D000080867:Gingipain Cysteine Endopeptidases; D008024:Ligands; D037521:Virulence Factors; D003546:Cysteine Endopeptidases