Adsorption of Components of the Plasma Kinin-Forming System on the Surface ofPorphyromonas gingivalisInvolves 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.

Activation of the Contact System at the Surface of Fusobacterium necrophorum Represents a Possible Virulence Mechanism in Lemièrre's Syndrome

“…Thus, the role of the contact system could be to promote a developing thrombus, which may provide a surface for assembly of the contact factors (32). Different surface molecules interact with HK, such as curli, fibrous proteins of Escherichia coli and Salmonella enterica serovar Typhimurium, the M protein of Streptococcus pyogenes (2,3), gingipains of Porphyromonas gingivalis (29), and lipopolysaccharide (26). Different regions of the HK molecule have been shown to bind to various cellular surfaces; domains D3, D4, and D5 of HK bind to platelets or endothelial cells (10)(11)(12)32), and D5 mediates binding and subsequent contact activation at bacterial surfaces (3,20).…”

Gingipains: Critical Factors in the Development of Aspiration Pneumonia Caused by <b><i>Porphyromonas gingivalis</i></b>

“…Furthermore, the aspiration of oral or gastric contents by young and healthy humans is an extremely rare event. The disease is mostly limited to individuals with an incompetent swallowing mechanism, such as stroke survivors, those with Parkinson’s disease or severe dementia, and users of antipsychotic drugs, proton pump inhibitors, and angiotensin-converting enzyme inhibitors; all of these factors tend to be associated with older individuals [55]. …”

<b><i>Porphyromonas gingivalis</i></b> Fimbriae Dampen P2X7-Dependent Interleukin-1β Secretion

“…Frozen stocks of WT P. gingivalis strain 381 and the major fimbriae mutant (DPG3) were previously described [20] and were grown anaerobically at 37°C on blood agar plates for 5 days as described [21]. Plate-grown organisms were used to inoculate liquid cultures of brain heart infusion broth (BD Biosciences) supplemented with yeast extract (0.5%; Sigma-Aldrich), hemin (10 μg/ml; Sigma-Aldrich), and menadione (1 μg/ml; Sigma-Aldrich).…”