title: Adsorption of components of the plasma kinin-forming system on the surface of Porphyromonas gingivalis involves gingipains as the major docking platforms.
abstract: Enhanced production of proinflammatory bradykinin-related peptides, the kinins, has been suggested to contribute to the pathogenesis of periodontitis, a common inflammatory disease of human gingival tissues. In this report, we describe a plausible mechanism of activation of the kinin-generating system, also known as the contact system or kininogen-kallikrein-kinin system, by the adsorption of its plasma-derived components such as high-molecular-mass kininogen (HK), prekallikrein (PK), and Hageman factor (FXII) to the cell surface of periodontal pathogen Porphyromonas gingivalis. The adsorption characteristics of mutant strains deficient in selected proteins of the cell envelope suggested that the surface-associated cysteine proteinases, gingipains, bearing hemagglutinin/adhesin domains (RgpA and Kgp) serve as the major platforms for HK and FXII adhesion. These interactions were confirmed by direct binding tests using microplate-immobilized gingipains and biotinylated contact factors. Other bacterial cell surface components such as fimbriae and lipopolysaccharide were also found to contribute to the binding of contact factors, particularly PK. Analysis of kinin release in plasma upon contact with P. gingivalis showed that the bacterial surface-dependent mechanism is complementary to the previously described kinin generation system dependent on HK and PK proteolytic activation by the gingipains. We also found that several P. gingivalis clinical isolates differed in the relative significance of these two mechanisms of kinin production. Taken together, these data show the importance of this specific type of bacterial surface-host homeostatic system interaction in periodontal infections.
authors.affiliation: Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Rapala-Kozik
authors.forename: Grazyna
authors.initials: G
authors.lastname: Bras
authors.forename: Barbara
authors.initials: B
authors.lastname: Chruscicka
authors.forename: Justyna
authors.initials: J
authors.lastname: Karkowska-Kuleta
authors.forename: Aneta
authors.initials: A
authors.lastname: Sroka
authors.forename: Heiko
authors.initials: H
authors.lastname: Herwald
authors.forename: Ky-Anh
authors.initials: KA
authors.lastname: Nguyen
authors.forename: Sigrun
authors.initials: S
authors.lastname: Eick
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kozik
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000327:Adsorption; D019921:Biotinylation; D002462:Cell Membrane; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D000080867:Gingipain Cysteine Endopeptidases; D007704:Kininogens / Q000235:genetics / Q000378:metabolism; D007705:Kinins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D007704:Kininogens; D007705:Kinins; D008565:Membrane Proteins; D003546:Cysteine Endopeptidases