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Plasmin inhibition by bacterial serpin: Implications in gum disease
- Source :
- Sochaj-Gregorczyk, A, Ksiazek, M, Waligorska, I, Straczek, A, Benedyk, M, Mizgalska, D, Thøgersen, I B, Enghild, J J & Potempa, J 2020, ' Plasmin inhibition by bacterial serpin : Implications in gum disease ', FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 34, no. 1, pp. 619-630 . https://doi.org/10.1096/fj.201901490RR, FASEB J
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Tannerella forsythia is a periodontopathogen that expresses miropin, a protease inhibitor in the serpin superfamily. In this study, we show that miropin is also a specific and efficient inhibitor of plasmin; thus it represents the first proteinaceous plasmin inhibitor of prokaryotic origin described to date. Miropin inhibits plasmin through the formation of a stable covalent complex triggered by cleavage of the Lys(368)-Thr(369) (P2-P1) reactive site bond with a stoichiometry of inhibition of 3.8 and an association rate constant (k(ass)) of 3.3×10(5) M(−1)s(-1). The inhibition of the fibrinolytic activity of plasmin was nearly as effective as that exerted by α(2)-antiplasmin. Miropin also acted in vivo by reducing blood loss in a mice tail bleeding assay. Importantly, intact T. forsythia cells or outer membrane vesicles, both of which carry surface-associated miropin, strongly inhibited plasmin. In intact bacterial cells, the antiplasmin activity of miropin protects envelope proteins from plasmin-mediated degradation. In summary, in the environment of periodontal pockets, which are bathed in gingival crevicular fluid consisting of 70% of blood plasma, an abundance of T. forsythia in the bacterial biofilm can cause local inhibition of fibrinolysis, which could have possible deleterious effects on the tooth-supporting structures of the periodontium.
- Subjects :
- 0301 basic medicine
Plasmin
medicine.medical_treatment
Serpin
Biochemistry
Article
03 medical and health sciences
0302 clinical medicine
Forsythia
In vivo
Catalytic Domain
Fibrinolysis
Genetics
medicine
Animals
Humans
Tannerella forsythia
Protease Inhibitors
Fibrinolysin
periodontitis
Molecular Biology
Periodontal Diseases
Serpins
plasmin
Bacteria
biology
Chemistry
serpin
Biofilm
biology.organism_classification
Antifibrinolytic Agents
Mice, Inbred C57BL
stomatognathic diseases
030104 developmental biology
Female
fibrinolysis
Bacterial outer membrane
030217 neurology & neurosurgery
Biotechnology
medicine.drug
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....b2a237075ab349f02798f59ef0d235da