OBJECTIVE: When @entity281 , @entity794 ( @entity16330 ) overcomes shear forces of flowing blood by binding to @entity2880 factor (VWF). Staphylococcal VWF-binding protein (vWbp) interacts with VWF, but it is unknown how this secreted protein binds to the bacterial cell wall. We hypothesized that vWbp interacts with a staphylococcal surface protein, mediating the adhesion of @entity16330 to VWF and vascular endothelium under shear stress. METHODS: We studied the binding of @entity16330 to vWbp, VWF and endothelial cells in a micro-parallel flow chamber using various mutants deficient in Sortase A (SrtA) and SrtA-dependent surface proteins, and @entity7878 expressing single staphylococcal surface proteins. In vivo adhesion of bacteria was evaluated in the @entity19 mesenteric circulation using real-time intravital vascular microscopy. RESULTS: vWbp bridges the bacterial cell wall and VWF, allowing shear-resistant binding of @entity16330 to inflamed or damaged endothelium. Absence of SrtA and Clumping factor A (ClfA) reduced adhesion of @entity16330 to vWbp, VWF and activated endothelial cells. ADAMTS13 and an anti-VWF A1 domain antibody, when combined reduced @entity16330 adhesion to activated endothelial cells by 90%. Selective overexpression of ClfA in the membrane of @entity7878 enabled these bacteria to bind to VWF and activated endothelial cells but only in the presence of vWbp. Absence of ClfA abolished bacterial adhesion to the activated @entity19 vessel wall. CONCLUSIONS: vWbp interacts with VWF and with the SrtA-dependent staphylococcal surface protein ClfA. The complex formed by VWF, secreted vWbp and bacterial ClfA anchors @entity16330 to vascular endothelium under shear stress. This article is protected by copyright. All rights reserved.

Clumping factor A, XXXX factor-binding protein and @entity2880 factor anchor @entity794 to the vessel wall.

@entity19 :: ('10090', 'Species') :: ['murine'] @entity794 :: ('1280', 'Species') :: ['Staphylococcus aureus'] @entity281 :: ('MESH:D007239', 'Disease') :: ['establishing endovascular infections'] @entity7878 :: ('1358', 'Species') :: ['Lactococcus lactis'] @entity2880 :: ('MESH:D014842', 'Disease') :: ['von Willebrand'] @entity16330 :: ('78380', 'Species') :: ['S. aureus']
@entity2880 :: (MESH:D014842,Disease) :: ['von Willebrand']
