PUBLICATION
Zebrafish as a new model to study effects of periodontal pathogens on cardiovascular diseases
- Authors
- Widziolek, M., Prajsnar, T.K., Tazzyman, S., Stafford, G.P., Potempa, J., Murdoch, C.
- ID
- ZDB-PUB-161026-8
- Date
- 2016
- Source
- Scientific Reports 6: 36023 (Journal)
- Registered Authors
- Prajsnar, Thomasz
- Keywords
- Bacterial pathogenesis, Pathogens
- MeSH Terms
-
- Adhesins, Bacterial/genetics
- Adhesins, Bacterial/metabolism*
- Animals
- Cardiovascular Diseases/microbiology*
- Cardiovascular Diseases/pathology
- Cysteine Endopeptidases/genetics
- Cysteine Endopeptidases/metabolism*
- Endothelium, Vascular/microbiology*
- Larva/microbiology
- Periodontitis/microbiology*
- Porphyromonas gingivalis/genetics
- Porphyromonas gingivalis/pathogenicity*
- Zebrafish/embryology
- PubMed
- 27777406 Full text @ Sci. Rep.
Citation
Widziolek, M., Prajsnar, T.K., Tazzyman, S., Stafford, G.P., Potempa, J., Murdoch, C. (2016) Zebrafish as a new model to study effects of periodontal pathogens on cardiovascular diseases. Scientific Reports. 6:36023.
Abstract
Porphyromonas gingivalis (Pg) is a keystone pathogen in the aetiology of chronic periodontitis. However, recent evidence suggests that the bacterium is also able to enter the bloodstream, interact with host cells and tissues, and ultimately contribute to the pathogenesis of cardiovascular disease (CVD). Here we established a novel zebrafish larvae systemic infection model showing that Pg rapidly adheres to and penetrates the zebrafish vascular endothelium causing a dose- and time-dependent mortality with associated development of pericardial oedemas and cardiac damage. The in vivo model was then used to probe the role of Pg expressed gingipain proteases using systemically delivered gingipain-deficient Pg mutants, which displayed significantly reduced zebrafish morbidity and mortality compared to wild-type bacteria. In addition, we used the zebrafish model to show efficacy of a gingipain inhibitor (KYT) on Pg-mediated systemic disease, suggesting its potential use therapeutically. Our data reveal the first real-time in vivo evidence of intracellular Pg within the endothelium of an infection model and establishes that gingipains are crucially linked to systemic disease and potentially contribute to CVD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping