Plasmin inhibition by bacterial serpin: Implications in gum disease

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Alicja Sochaj-Gregorczyk, Malopolska Center of Biotechnology, Jagiellonian University, Krakow, Poland.
  • ,
  • Miroslaw Ksiazek, Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, USA.
  • ,
  • Irena Waligorska, Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
  • ,
  • Anna Straczek, Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
  • ,
  • Malgorzata Benedyk, Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
  • ,
  • Danuta Mizgalska, Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
  • ,
  • Ida B Thøgersen
  • ,
  • Jan J Enghild
  • Jan Potempa, Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, USA.

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 Lys368-Thr369 (P2-P1) reactive site bond with a stoichiometry of inhibition of 3.8 and an association rate constant (kass) of 3.3 × 105 M-1s-1. The inhibition of the fibrinolytic activity of plasmin was nearly as effective as that exerted by α2-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.

OriginalsprogEngelsk
TidsskriftFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Vol/bind34
Nummer1
Sider (fra-til)619-630
Antal sider12
ISSN0892-6638
DOI
StatusUdgivet - 2020

Se relationer på Aarhus Universitet Citationsformater

ID: 176407833