PUBLICATION
Mechanisms of vascular damage by systemic dissemination of the oral pathogen Porphyromonas gingivalis
- Authors
- Farrugia, C., Stafford, G.P., Potempa, J., Wilkinson, R.N., Chen, Y., Murdoch, C., Widziolek, M.
- ID
- ZDB-PUB-200719-18
- Date
- 2020
- Source
- The FEBS journal 288(5): 1479-1495 (Journal)
- Registered Authors
- Wilkinson, Robert
- Keywords
- Porphyromonas gingivalis, Cardiovascular disease, endothelial cells, gingipain, periodontal disease
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Antigens, CD/genetics
- Antigens, CD/metabolism
- Bacteroidaceae Infections/etiology*
- Bacteroidaceae Infections/genetics
- Bacteroidaceae Infections/metabolism
- Bacteroidaceae Infections/pathology
- Cadherins/genetics
- Cadherins/metabolism
- Capillary Permeability/drug effects
- Cardiomegaly/etiology*
- Cardiomegaly/genetics
- Cardiomegaly/metabolism
- Cardiomegaly/pathology
- Edema/etiology*
- Edema/genetics
- Edema/metabolism
- Edema/pathology
- Embryo, Nonmammalian
- Endothelial Cells/drug effects*
- Endothelial Cells/metabolism
- Endothelial Cells/pathology
- Fluorescein Angiography
- Gene Expression/drug effects
- Genes, Reporter
- Gingipain Cysteine Endopeptidases/biosynthesis
- Gingipain Cysteine Endopeptidases/toxicity*
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Humans
- Larva/drug effects
- Larva/microbiology
- Platelet Endothelial Cell Adhesion Molecule-1/genetics
- Platelet Endothelial Cell Adhesion Molecule-1/metabolism
- Porphyromonas gingivalis/growth & development
- Porphyromonas gingivalis/metabolism
- Porphyromonas gingivalis/pathogenicity*
- Primary Cell Culture
- Signal Transduction
- Zebrafish
- PubMed
- 32681704 Full text @ FEBS J.
Citation
Farrugia, C., Stafford, G.P., Potempa, J., Wilkinson, R.N., Chen, Y., Murdoch, C., Widziolek, M. (2020) Mechanisms of vascular damage by systemic dissemination of the oral pathogen Porphyromonas gingivalis. The FEBS journal. 288(5):1479-1495.
Abstract
Several studies have shown a clear association between periodontal disease and increased risk of cardiovascular disease. Porphyromonas gingivalis (Pg), a key oral pathogen, and its cell surface expressed gingipains, induce oedema in a zebrafish larvae infection model although the mechanism of these vascular effects is unknown. Here we aimed to determine whether Pg-induced vascular damage is mediated by gingipains. In vitro, human endothelial cells from different vascular beds were invaded by wild-type (W83) but not gingipain-deficient (ΔK/R-ab) Pg. W83 infection resulted in increased endothelial permeability as well as decreased cell surface abundance of endothelial adhesion molecules PECAM-1 and VE-cadherin compared to infection with ΔK/R-ab. In agreement, when transgenic zebrafish larvae expressing fluorescently labelled PECAM-1 or VE-cadherin were systemically infected with W83 or ΔK/R-ab, a significant reduction in adhesion molecule fluorescence was observed specifically in endothelium proximal to W83 bacteria through a gingipain dependent mechanism. Furthermore, this was associated with increased vascular permeability in vivo when assessed by dextran leakage microangiography. These data are the first to show that Pg directly mediates vascular damage in vivo by degrading PECAM-1 and VE-cadherin. Our data provide a molecular mechanism by which Pg might contribute to cardiovascular disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping