scholarly journals Effect of Zymogen Domains and Active Site Occupation on Activation of Prothrombin by von Willebrand Factor-binding Protein

2012 ◽  
Vol 287 (46) ◽  
pp. 39149-39157 ◽  
Author(s):  
Heather K. Kroh ◽  
Paul E. Bock
Keyword(s):  
Von Willebrand Factor ◽  
Active Site ◽  
Binding Protein ◽  
Factor Binding ◽  
Site Occupation ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Adaptation of Staphylococcus aureus to ruminant and equine hosts involves SaPI-carried variants of von Willebrand factor-binding protein

2010 ◽  
Vol 77 (6) ◽  
pp. 1583-1594 ◽  
Author(s):  
David Viana ◽  
José Blanco ◽  
María Ángeles Tormo-Más ◽  
Laura Selva ◽  
Caitriona M. Guinane ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Von Willebrand Factor ◽  
Binding Protein ◽  
Factor Binding ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals The Expression of von Willebrand Factor-Binding Protein Determines Joint-Invading Capacity of Staphylococcus aureus, a Core Mechanism of Septic Arthritis

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Manli Na ◽  
Zhicheng Hu ◽  
Majd Mohammad ◽  
Mariana do Nascimento Stroparo ◽  
Abukar Ali ◽  
...  
Keyword(s):  
Septic Arthritis ◽  
Von Willebrand Factor ◽  
Binding Protein ◽  
Joint Diseases ◽  
Wild Type ◽  
Content Type ◽  
Factor Binding ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Deficient Mice

ABSTRACT Septic arthritis, one of the most dangerous joint diseases, is predominantly caused by Staphylococcus aureus. In contrast, coagulase-negative staphylococci are rarely found in septic arthritis. We hypothesize that coagulases released by S. aureus, including coagulase (Coa) and von Willebrand factor-binding protein (vWbp), play potent roles in the induction of septic arthritis. Four isogenic S. aureus strains differing in expression of coagulases (wild-type [WT] Newman, Δcoa, Δvwb, and Δcoa Δvwb) were used to induce septic arthritis in both wild-type and von Willebrand factor (vWF)-deficient mice. Septic arthritis severity was greatly reduced when wild-type mice were infected with the Δcoa Δvwb and Δvwb variants compared to WT or Δcoa strains, suggesting that vWbp rather than Coa is a major virulence factor in S. aureus septic arthritis. vWF-deficient mice were more susceptible to bone damage in septic arthritis, especially when the Δvwb strain was used. Importantly, no difference in arthritis severity between the Δvwb and WT strains was observed in vWF-deficient mice. Collectively, we conclude that vWbp production by S. aureus enhances staphylococcal septic arthritis. IMPORTANCE Septic arthritis remains one of the most dangerous joint diseases with a rapidly progressive disease character. Despite advances in the use of antibiotics, permanent reductions in joint function due to joint deformation and deleterious contractures occur in up to 50% of patients with septic arthritis. So far, it is still largely unknown how S. aureus initiates and establishes joint infection. Here, we demonstrate that von Willebrand factor-binding protein expressed by S. aureus facilitates the initiation of septic arthritis. Such effect might be mediated through its interaction with a host factor (von Willebrand factor). Our finding contributes significantly to the full understanding of septic arthritis etiology and will pave the way for new therapeutic modalities for this devastating disease.

scholarly journals Multimodal imaging of bacterial-host interface in mice and piglets with Staphylococcus aureus endocarditis

2020 ◽  
Vol 12 (568) ◽  
pp. eaay2104
Author(s):  
Peter Panizzi ◽  
Marvin Krohn-Grimberghe ◽  
Edmund Keliher ◽  
Yu-Xiang Ye ◽  
Jana Grune ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Von Willebrand Factor ◽  
Immune Cell ◽  
Binding Protein ◽  
Thrombin Inhibitor ◽  
Bacterial Colony ◽  
Factor Binding ◽  
Von Willebrand ◽  
Willebrand Factor

Acute bacterial endocarditis is a rapid, difficult to manage, and frequently lethal disease. Potent antibiotics often cannot efficiently kill Staphylococcus aureus that colonizes the heart’s valves. S. aureus relies on virulence factors to evade therapeutics and the host’s immune response, usurping the host’s clotting system by activating circulating prothrombin with staphylocoagulase and von Willebrand factor–binding protein. An insoluble fibrin barrier then forms around the bacterial colony, shielding the pathogen from immune cell clearance. Targeting virulence factors may provide previously unidentified avenues to better diagnose and treat endocarditis. To tap into this unused therapeutic opportunity, we codeveloped therapeutics and multimodal molecular imaging to probe the host-pathogen interface. We introduced and validated a family of small-molecule optical and positron emission tomography (PET) reporters targeting active thrombin in the fibrin-rich environment of bacterial colonies. The imaging agents, based on the clinical thrombin inhibitor dabigatran, are bound to heart valve vegetations in mice. Using optical imaging, we monitored therapy with antibodies neutralizing staphylocoagulase and von Willebrand factor–binding protein in mice with S. aureus endocarditis. This treatment deactivated bacterial defenses against innate immune cells, decreased in vivo imaging signal, and improved survival. Aortic or tricuspid S. aureus endocarditis in piglets was also successfully imaged with clinical PET/magnetic resonance imaging. Our data map a route toward adjuvant immunotherapy for endocarditis and provide efficient tools to monitor this drug class for infectious diseases.

scholarly journals Adhesion of Staphylococcus aureus to the vessel wall under flow is mediated by von Willebrand factor–binding protein

Blood ◽  
2014 ◽  
Vol 124 (10) ◽  
pp. 1669-1676 ◽  
Author(s):  
Jorien Claes ◽  
Thomas Vanassche ◽  
Marijke Peetermans ◽  
Laurens Liesenborghs ◽  
Christophe Vandenbriele ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Endothelial Cells ◽  
Von Willebrand Factor ◽  
Vessel Wall ◽  
Binding Protein ◽  
Factor Binding ◽  
Key Points ◽  
Platelet Aggregates ◽  
Von Willebrand ◽  
Willebrand Factor

Key PointsvWbp mediates adhesion of S aureus under flow to activated endothelial cells and the subendothelium via VWF. vWbp activates prothrombin and triggers the formation of bacteria–fibrin–platelet aggregates, which enhance adhesion to vessels under flow.

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