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Plasmin inhibition by bacterial serpin: Implications in gum disease
Author(s) -
SochajGregorczyk Alicja,
Ksiazek Miroslaw,
Waligorska Irena,
Straczek Anna,
Benedyk Malgorzata,
Mizgalska Danuta,
Thøgersen Ida B.,
Enghild Jan J.,
Potempa Jan
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901490rr
Subject(s) - plasmin , chemistry , serpin , fibrinolysis , protease , biochemistry , in vivo , microbiology and biotechnology , biophysics , enzyme , biology , psychology , psychiatry , gene
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.