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Updated: Dec 31, 2025
Porphyromonas gingivalis as a Model Organism for Assessing Interaction of Anaerobic Bacteria with Host Cells
Published on: December 17, 2015
Plasmin inhibition by bacterial serpin: Implications in gum disease
Alicja Sochaj-Gregorczyk1, Miroslaw Ksiazek1,2,3, Irena Waligorska2
1Malopolska Center of Biotechnology, Jagiellonian University, Krakow, Poland.
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 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.
Insights
Tannerella forsythia produces miropin, a novel prokaryotic plasmin inhibitor. This bacterial protease inhibitor found in periodontal pockets can locally inhibit fibrinolysis, potentially harming tooth-supporting structures.
Area of Science:
- Microbiology
- Biochemistry
- Periodontology
Background:
- Tannerella forsythia is a key periodontopathogen.
- Protease inhibitors regulate physiological processes.
- Plasmin plays a role in tissue remodeling and inflammation.
Purpose of the Study:
- To characterize miropin as a plasmin inhibitor.
- To investigate the origin and function of miropin.
- To assess the role of miropin in periodontal disease pathogenesis.
Main Methods:
- Biochemical assays to determine miropin's inhibitory activity against plasmin.
- Analysis of miropin-plasmin complex formation and kinetics.
- In vivo studies using a mouse tail bleeding model.
- Investigation of miropin's effect on T. forsythia cells and outer membrane vesicles.
Main Results:
- Miropin is a specific and efficient inhibitor of plasmin, forming a stable covalent complex.
- It is the first described proteinaceous plasmin inhibitor of prokaryotic origin.
- Miropin effectively inhibits plasmin's fibrinolytic activity in vitro and reduces blood loss in vivo.
- Surface-associated miropin on T. forsythia cells inhibits plasmin and protects bacterial envelope proteins.
Conclusions:
- Miropin represents a novel class of plasmin inhibitors derived from bacteria.
- Local inhibition of fibrinolysis by T. forsythia in periodontal pockets may contribute to periodontitis progression.
- Miropin's anti-plasmin activity has implications for understanding host-pathogen interactions in periodontitis.
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