Journal ArticleDOI
The Role of Gingipains in the Pathogenesis of Periodontal Disease
TLDR
Based on the important activities of gingipains in the bacterial infection and the pathogenesis of periodontitis, the bacterial proteinases can be targets for periodontal disease therapy.Abstract:
Gingipains are trypsin-like cysteine proteinases produced by Porphyromonas gingivalis, a major causative bacterium of adult periodontitis. HRgpA (95 kDa) and RgpB (50 kDa), products of 2 distinct but related genes, rgpA and rgpB, respectively, are specific for Arg-Xaa peptide bonds. Kgp, a product of the kgp gene, is specific for Lys-Xaa bonds. HRgpA and Kgp are non-covalent complexes containing separate catalytic and adhesion/ hemagglutinin domains, while RgpB has only a catalytic domain with a primary structure essentially identical to that of the catalytic subunit of HRgp. HRgpA and RgpB induce vascular permeability enhancement through activation of the kallikrein/kinin pathway and activate the blood coagulation system, which, respectively, are potentially associated with gingival crevicular fluid production and progression of inflammation leading to alveolar bone loss in the periodontitis site. Kgp is the most potent fibrinogen/fibrin degrading enzyme of the 3 gingipains in human plasma and is involved in the bleeding tendency at the diseased gingiva. HRgpA activates coagulation factors and degrades fibrinogen/fibrin more efficiently than RgpB due to the adhesion/hemagglutinin domains, which have affinity for phospholipids and fibrinogen. Gingipains degrade macrophage CD14, thus inhibiting activation of the leukocytes through the lipopolysaccharide (LPS) receptor, and thereby facilitating sustained colonization of P. gingivalis. Gingipains play a role in bacterial housekeeping and infection, including amino acid uptake from host proteins and fimbriae maturation. Based on the important activities of gingipains in the bacterial infection and the pathogenesis of periodontitis, the bacterial proteinases can be targets for periodontal disease therapy. Immunization with RgpB, HRgpA, or a portion of HRgpA catalytic domain attenuated P. gingivalis induced disorders in mice. In addition, a trypsin-like proteinase inhibitor retarded P. gingivalis growth specifically. Gingipains are potent virulence factors of P. gingivalis, and are likely to be associated with the development of periodontitis. It is, therefore, suggested that gingipain inhibition by vaccination and gingipain-specific inhibitors is a useful therapy for adult periodontitis caused by P. gingivalis infection.read more
Citations
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Journal ArticleDOI
Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: The 'red complex', a prototype polybacterial pathogenic consortium in periodontitis
Journal ArticleDOI
Host response mechanisms in periodontal diseases
Nora Silva,Loreto Abusleme,Denisse Bravo,Nicolas Dutzan,Jocelyn García-Sesnich,Rolando Vernal,Marcela Hernández,Jorge Gamonal +7 more
TL;DR: A characterization of the progression ofperiodontitis as a stage that presents a significantly host immune and inflammatory response to the microbial challenge that determine of susceptibility to develop the destructive/progressive periodontitis under the influence of multiple behavioral, environmental and genetic factors.
Journal ArticleDOI
The Junctional Epithelium: from Health to Disease:
TL;DR: The junctional epithelium is located at a strategically important interface between the gingival sulcus, populated with bacteria, and the periodontal soft and mineralized connective tissues that need protection from becoming exposed to bacteria and their products.
Journal ArticleDOI
Dichotomy of gingipains action as virulence factors: from cleaving substrates with the precision of a surgeon’s knife to a meat chopper‐like brutal degradation of proteins
TL;DR: Gingipains are absolutely essential for bacterial survival/proliferation in vivo and for the pathological outcome of the experimental infection of P. gingivalis, the most prevailing form of periodontal disease.
Journal ArticleDOI
Community-wide transcriptome of the oral microbiome in subjects with and without periodontitis.
Ana E. Duran-Pinedo,Tsute Chen,Ricardo Teles,Jacqueline R. Starr,Xiaoshan Wang,Keerthana Krishnan,Jorge Frias-Lopez +6 more
TL;DR: The overall picture of metabolic activities showed that iron acquisition, lipopolysaccharide synthesis and flagellar synthesis were major activities defining disease, and the vast majority of virulence factors upregulated in subjects with periodontitis came from organisms that are not considered major periodontal pathogens.
References
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Journal ArticleDOI
Microbiology of periodontal disease
TL;DR: This review is based on a discussion at the 1986 Annual Meeting of the American Association of Dental Research of recent literature in this field which primarily concerned all of the relevant papers that were available to me and that had been published in the last 2 years.
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The use of crevicular fluid prostaglandin E2 levels as a predictor of periodontal attachment loss
TL;DR: Analysis of MCF-PGE levels as a screening test indicate that this measurement has a high degree of sensitivity, specificity, and a predictive value of 0.92–0.95, which has significant merit as a diagnostic tool to determine if a patient is in a state of remission or about to undergo an attachment loss episode.
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Implantation of Bacteroides gingivalis in nonhuman primates initiates progression of periodontitis
TL;DR: The successful implantation of a rifampin-resistant strain of the putativeperiodontal pathogen Bacteroides gingivalis into the periodontal microbiota of monkeys resulted in an increase in the systemic levels of antibody to the microorganism and rapid and significant bone loss.
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Measurement of interleukin-1 alpha and -1 beta in gingival crevicular fluid: implications for the pathogenesis of periodontal disease.
TL;DR: It is demonstrated that IL-1 is produced and released locally in periodontal disease at concentrations sufficient to mediate tissue inflammation and bone resorption and may serve as a marker ofperiodontal tissue destruction.
Journal ArticleDOI
Role of bacterial proteinases in matrix destruction and modulation of host responses
TL;DR: Gingipains seem to be key players in subverting host defense systems with, significantly, the complement and neutrophils being the main target and a strong effect on mechanisms controlling host matrix metalloproteinase activity at the level of gene expression and zymogen activation.