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.
Highlights
Staphylococcus aureus manipulates blood coagulation by secreting von Willebrand factor binding protein and coagulase
We used affinity chromatography with non-catalytic Coa and von Willebrand factor binding protein (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
FXIII bound to the C1 and C2 truncations but not to the C3 no the C4 variants (Fig. 2, B and C). These results suggest that FXIII requires the D1 and D2 domains as well as the central domain of vWbp for binding
Summary
Staphylococcus aureus manipulates blood coagulation by secreting von Willebrand factor binding protein (vWbp) and coagulase. 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. 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. Microbial recognition by pathogen-associated molecular pattern recognition receptors triggers the release of cytokines, which activate the extrinsic blood coagulation cascade, thereby depositing fibrin around bacterial invaders (11). Exploiting the presence of coagulation factors in their zymogen form in the bloodstream, all clinical isolates of S. aureus secrete two hemostasis factors, coagulase (Coa) (12) and von Willebrand factor binding protein (vWbp) (13), that bind to and activate prothrombin in a non-proteolytic manner (14).
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