title: Streptococcus pyogenes triggers activation of the human contact system by streptokinase.
abstract: Severe invasive infectious diseases remain a major and life-threatening health problem. In serious cases, a systemic activation of the coagulation cascade is a critical complication that is associated with high mortality rates. We report here that streptokinase, a group A streptococcal plasminogen activator, triggers the activation of the human contact system. Activation of contact system factors at the surface of the Streptococcus pyogenes serotype M49 is dependent on streptokinase and plasminogen. Our results also show that secreted streptokinase is an efficient contact system activator, independent from a contact surface. This results in the processing of high-molecular-weight kininogen and the release of bradykinin, a potent vascular mediator. We further investigated whether the ability of 50 different clinical S. pyogenes isolates to activate the contact system is associated with an invasive phenotype. The data reveal that isolates from invasive infections trigger an activation of the contact system more potently than strains isolated from noninvasive infections. The present study gives new insights into the mechanisms by which S. pyogenes triggers the human contact system and stresses the function of soluble and surface located plasmin exploited as a group A streptococcal virulence factor through the action of streptokinase.
authors.affiliation: Institute of Medical Microbiology, Virology, and Hygiene, Rostock University Medical Centre, Rostock, Germany
authors.forename: Ramona
authors.initials: R
authors.lastname: Nitzsche
authors.forename: Maik
authors.initials: M
authors.lastname: Rosenheinrich
authors.forename: Bernd
authors.initials: B
authors.lastname: Kreikemeyer
authors.forename: Sonja
authors.initials: S
authors.lastname: Oehmcke-Hecht
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005174:Factor XII / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D010958:Plasminogen / Q000235:genetics / Q000378:metabolism; D011288:Prekallikrein / Q000235:genetics / Q000378:metabolism; D013290:Streptococcal Infections / Q000201:enzymology / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000235:genetics; D013300:Streptokinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D005174:Factor XII; D010958:Plasminogen; D011288:Prekallikrein; D013300:Streptokinase