title: Zebrafish as a new model to study effects of periodontal pathogens on cardiovascular diseases.
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.
authors: Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors: Magdalena
authors: M
authors: Widziolek
authors: The Batson Centre, University of Sheffield, Sheffield, UK.|The Krebs Institute, Department of Molecular Biology and Microbiology, University of Sheffield, Sheffield, UK.
authors: Tomasz K
authors: TK
authors: Prajsnar
authors: Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
authors: Simon
authors: S
authors: Tazzyman
authors: School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
authors: Graham P
authors: GP
authors: Stafford
authors: Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.|Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, USA.
authors: Jan
authors: J
authors: Potempa
authors: School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
authors: Craig
authors: C
authors: Murdoch
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002318:Cardiovascular Diseases / Q000382:microbiology* / Q000473:pathology; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000382:microbiology*; D000080867:Gingipain Cysteine Endopeptidases; D007814:Larva / Q000382:microbiology; D010518:Periodontitis / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000472:pathogenicity*; D015027:Zebrafish / Q000196:embryology
chemical_list: D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D003546:Cysteine Endopeptidases