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Updated: May 8, 2026

In Vitro and In Vivo Model to Study Bacterial Adhesion to the Vessel Wall Under Flow Conditions
Published on: June 11, 2015
Multiple ligands of von Willebrand factor-binding protein (vWbp) promote Staphylococcus aureus clot formation in
Lena Thomer1, Olaf Schneewind, Dominique Missiakas
1From the Department of Microbiology, University of Chicago, Chicago, Illinois 60637.
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.
Insights
Staphylococcus aureus virulence factors, coagulase (Coa) and von Willebrand factor-binding protein (vWbp), bind plasma proteins like prothrombin and fibrinogen. This interaction promotes blood clot formation and aids bacterial infection establishment.
Area of Science:
- Microbiology
- Biochemistry
- Infectious Diseases
Background:
- Staphylococcus aureus utilizes virulence factors like coagulase (Coa) and von Willebrand factor-binding protein (vWbp) to manipulate host prothrombin, facilitating infection.
- Coa and vWbp's D1-D2 domains activate prothrombin non-proteolytically, while Coa binds fibrinogen and vWbp binds von Willebrand factor and fibrinogen.
Purpose of the Study:
- To identify plasma protein ligands for S. aureus Coa and vWbp using affinity chromatography.
- To elucidate the role of these interactions in Staphylococcus aureus-mediated coagulation and virulence.
Main Methods:
- Affinity chromatography using non-catalytic Coa and vWbp.
- Analysis of protein-protein interactions in human plasma.
- In vitro functional assays for Factor XIII activation.
Main Results:
- vWbp bound prothrombin, fibrinogen, fibronectin, and Factor XIII (FXIII).
- Coa bound prothrombin and fibrinogen.
- vWbp-mediated FXIII activation required prothrombin and occurred non-proteolytically.
- Staphylococcal coagulation involved prothrombin, FXIII, fibronectin recruitment, and cross-linked fibrin formation.
Conclusions:
- Coa and vWbp bind distinct but overlapping sets of host plasma proteins.
- vWbp contributes to both non-proteolytic FXIII activation and prothrombin activation, enhancing S. aureus virulence.
- The identified interactions are crucial for Staphylococcus aureus-induced coagulation and infection progression.
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