title: Multiple ligands of von Willebrand factor-binding protein (vWbp) promote Staphylococcus aureus clot formation in human plasma.
abstract: Staphylococcus aureus secretes coagulase (Coa) and von Willebrand factor-binding protein (vWbp) to activate host prothrombin and form fibrin cables, thereby promoting the establishment of infectious lesions. The D1-D2 domains of Coa and vWbp associate with, and non-proteolytically activate prothrombin. Moreover, Coa encompasses C-terminal tandem repeats for binding to fibrinogen, whereas vWbp has been reported to associate with von Willebrand factor and fibrinogen. Here we used affinity chromatography with non-catalytic Coa and vWbp to identify the ligands for these virulence factors in human plasma. vWbp bound to prothrombin, fibrinogen, fibronectin, and factor XIII, whereas Coa co-purified with prothrombin and fibrinogen. vWbp association with fibrinogen and factor XIII, but not fibronectin, required prothrombin and triggered the non-proteolytic activation of FXIII in vitro. Staphylococcus aureus coagulation of human plasma was associated with the recruitment of prothrombin, FXIII, and fibronectin as well as the formation of cross-linked fibrin. FXIII activity in staphylococcal clots could be attributed to thrombin-dependent proteolytic activation as well as vWbp-mediated non-proteolytic activation of FXIII zymogen.
authors: From the Department of Microbiology, University of Chicago, Chicago, Illinois 60637.
authors: Lena
authors: L
authors: Thomer
authors: Olaf
authors: O
authors: Schneewind
authors: Dominique
authors: D
authors: Missiakas
mesh_terms: D001426:Bacterial Proteins / Q000097:blood / Q000378:metabolism*; D001777:Blood Coagulation; D003030:Coagulase / Q000097:blood / Q000378:metabolism; D005176:Factor XIII / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011516:Prothrombin / Q000378:metabolism; D013203:Staphylococcal Infections / Q000097:blood*; D013211:Staphylococcus aureus / Q000378:metabolism / Q000472:pathogenicity; D037521:Virulence Factors / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D003030:Coagulase; D005353:Fibronectins; D008024:Ligands; D046911:Macromolecular Substances; D037521:Virulence Factors; D014841:von Willebrand Factor; D011516:Prothrombin; D005340:Fibrinogen; D005176:Factor XIII
keywords: Coagulase; Coagulation Factors; Factor XIII; Fibrin; Fibrinogen; Fibronectin; Staphylococcus aureus; vWbp
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