title: Interactions between surface proteins of Streptococcus pyogenes and coagulation factors modulate clotting of human plasma.
abstract: Invasive and toxic infections caused by Streptococcus pyogenes are connected with high morbidity and mortality. Typical symptoms of these infections are hypotension, edema formation, tissue necrosis, and bleeding disorders. Here we report that components of the coagulation system including fibrinogen, factors V, XI, and XII, and H-kininogen, are assembled at the surface of S. pyogenes through specific interactions with bacterial surface proteins. In plasma environment, absorption of fibrinogen by S. pyogenes causes a hypocoagulatory state resulting in prolonged clotting times and impaired fibrin network formation. Moreover, the binding of coagulation factors and the subsequent activation of the coagulation system at the bacterial surface lead to the formation of a fibrin network covering S. pyogenes bacteria adhering to epithelial cells. The results suggest that interactions between S. pyogenes and components of the coagulation system contribute to some of the symptoms seen in severe infections caused by this important human pathogen.
authors.affiliation: Department of Cell and Molecular Biology, Section for Molecular Pathogenesis, Lund University, Lund, Sweden. Heiko.Herwald@medkem.lu.se
authors.forename: H
authors.initials: H
authors.lastname: Herwald
authors.forename: M
authors.initials: M
authors.lastname: Mörgelin
authors.forename: B
authors.initials: B
authors.lastname: Dahlbäck
authors.forename: L
authors.initials: L
authors.lastname: Björck
mesh_terms: D000942:Antigens, Bacterial; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D001426:Bacterial Proteins / Q000502:physiology*; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology / Q000648:ultrastructure; D005337:Fibrin / Q000378:metabolism / Q000648:ultrastructure; D005342:Fibrinolysis; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000502:physiology; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D013290:Streptococcal Infections / Q000097:blood; D013297:Streptococcus pyogenes / Q000472:pathogenicity* / Q000502:physiology / Q000648:ultrastructure
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001779:Blood Coagulation Factors; D002352:Carrier Proteins; D008565:Membrane Proteins; C064006:protein H, Streptococcus; C014689:streptococcal M protein; D005337:Fibrin