SCM, a novel M-like protein from Streptococcus canis binds (Mini)-plasminogen with high affinity and facilitates bacterial transmigration
Résumé
Streptococcus canis is an important zoonotic pathogen capable of causing serious invasive diseases in domestic animals and humans. In this study we report the binding of human plasminogen to S. canis and the recruitment of proteolytically active plasmin on its surface. The binding receptor for plasmin-ogen was identified as a novel M-like protein designated S. canis M-like protein (SCM). Surface plasmon resonance analyses, radio-active dot blot analyses and heterologous expression on the surface of S. gordonii confirmed the plasminogen-binding capa-bility of SCM. The binding domain was located within the N-terminus of SCM, which specifically bound to the C-terminal part of plasminogen (mini-plasminogen) comprising kringle domain 5 and the catalytic domain. In the presence of urokinase, SCM mediated plasminogen activation on the bacterial surface that was inhibited by serine protease inhibitors and lysine amino acid analogues. Surface-bound plasmin effectively degraded purified fibrinogen as well as fibrin clots, resulting in the dissolution of fibrin thrombi. Electron microscopic illustration and time lapse imaging demonstrated bacterial transmigration through fibrinous thrombi. This study led for the first time to the identification of SCM as novel receptor for (mini)-plasminogen mediating fibrinolytic activity of S. canis.
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