Scientists from Proteolysis and Post-translational Modification of Proteins Research Group at the MCB in collaboration with researchers from JU Department of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology have recently published a paper that focuses on a bacterial protease inhibitor called miropin and its possible implication in periodontitis.
Periodontitis, also known as gum disease, is a chronic inflammation that progressively destroys the soft tissues and bones, which are surrounding, and supporting teeth. This condition affects up to 50% of the adult population worldwide and is the major cause of tooth loss. The onset of periodontitis is marked by the dysbiosis of oral microbiota inhabiting periodontal pockets. Tannerella forsythia belongs to the bacterial species whose overrepresentation in the dental plaque correlates with the development and progression of periodontitis.
T. forsythia expresses miropin, a protease inhibitor in the serpin (serine protease inhibitors) superfamily. Miropin, similarly to other serpins, forms a covalent complex with a protease, ultimately resulting in an extensive conformational change of the inhibitor and partial denaturation of its target. However, unlike the vast majority serpins, miropin can inhibit multiple serine and cysteine proteases of various specificities.
Miropin-dependent inhibition of plasmin
In a paper recently published in the FASEB Journal, researchers show that T. forsythia cells or outer membrane vesicles, both of which carry surface‐associated miropin, strongly inhibited human plasmin, the protease responsible for fibrin clot resolution (fibrinolysis), but none of the coagulation proteases. Moreover, miropin also acted in vivo by reducing blood loss in a mice tail bleeding assay. This makes miropin the first proteinaceous plasmin inhibitor of prokaryotic origin described to date. The biological significance of miropin-dependent inhibition of plasmin in the context of periodontitis was further proposed in the paper. 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.
It should be stressed that both in human and mice deficiencies in plasmin activity result in development of periodontitis.
The manuscript, entitled “Plasmin inhibition by bacterial serpin: Implications in gum disease” was published in the FASEB Journal on 26 November 2019 (the full-text article can be found here)
Written by Alicja Sochaj-Gregorczyk