title: SCM, a novel M-like protein from Streptococcus canis, binds (mini)-plasminogen with high affinity and facilitates bacterial transmigration.
abstract: Streptococcus canis is an important zoonotic pathogen capable of causing serious invasive diseases in domestic animals and humans. In the present paper we report the binding of human plasminogen to S. canis and the recruitment of proteolytically active plasmin on its surface. The binding receptor for plasminogen was identified as a novel M-like protein designated SCM (S. canis M-like protein). SPR (surface plasmon resonance) analyses, radioactive dot-blot analyses and heterologous expression on the surface of Streptococcus gordonii confirmed the plasminogen-binding capability 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. The present study has led, for the first time, to the identification of SCM as a novel receptor for (mini)-plasminogen mediating the fibrinolytic activity of S. canis.
authors.affiliation: Department of Medical Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany. Marcus.Fulde@helmholtz-hzi.de
authors.forename: Marcus
authors.initials: M
authors.lastname: Fulde
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.forename: Angela
authors.initials: A
authors.lastname: Hitzmann
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.forename: D Patric
authors.initials: DP
authors.lastname: Nitsche-Schmitz
authors.forename: Andreas
authors.initials: A
authors.lastname: Nerlich
authors.forename: Gursharan Singh
authors.initials: GS
authors.lastname: Chhatwal
authors.forename: Simone
authors.initials: S
authors.lastname: Bergmann
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D020134:Catalytic Domain; D002415:Cats; D004285:Dogs; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D018082:Kringles; D010949:Plasma; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D013291:Streptococcus / Q000302:isolation & purification / Q000502:physiology*; D013552:Swine
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; C084529:plasminogen-binding protein, bacteria; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D005341:Fibrinolysin