Shear-Resistant Binding to von Willebrand Factor Allows Staphylococcus lugdunensis to Adhere to the Cardiac Valves and Initiate Endocarditis
Shear-Resistant Binding to von Willebrand Factor Allows Staphylococcus lugdunensis to Adhere to the Cardiac Valves and Initiate Endocarditis
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DOI：
10.1093/infdis/jiv773
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发表时间：
2016-04-01
影响因子：
6.4
通讯作者：
Verhamme, Peter
中科院分区：
文献类型：
--
作者：
Liesenborghs, Laurens;Peetermans, Marijke;Verhamme, Peter
背景路邓葡萄球菌是心内膜炎的一种新的病因。引起血管内感染，S。lugdunensis需要克服剪切应力的机制。我们研究了血小板和血管性血友病因子（VWF）是否介导细菌粘附到血管壁和流动下的心脏瓣膜。S.在不存在和存在血小板的情况下，在平行流动室中研究了Lugdunensis与VWF、胶原和内皮细胞的结合。在体内粘附S.在小鼠微血管灌注模型和新的小鼠心内膜炎模型中评价lugdunensis。与其它凝固酶阴性葡萄球菌不同，S. Lugdunensis在流动下与VWF结合，从而使其能够粘附于内皮细胞和内皮下基质。在肠系膜循环的炎症血管中，VWF募集S。lugdunensis的血管壁。在一种新的心内膜炎小鼠模型中，局部炎症和VWF的释放使S。结论：Lugdunensis能够在心脏瓣膜上定植。S. Lugdunensis直接与VWF结合，VWF被证明对于承受剪切力以及对于其与血管壁和心脏瓣膜的粘附至关重要。这一机制解释了S.与其他凝固酶阴性葡萄球菌相比，路邓葡萄球菌引起更严重的感染，包括心内膜炎。
Background. Staphylococcus lugdunensis is an emerging cause of endocarditis. To cause endovascular infections, S. lugdunensis requires mechanisms to overcome shear stress. We investigated whether platelets and von Willebrand factor (VWF) mediate bacterial adhesion to the vessel wall and the cardiac valves under flow.Methods. S. lugdunensis binding to VWF, collagen, and endothelial cells was studied in a parallel flow chamber in the absence and presence of platelets. In vivo adhesion of S. lugdunensis was evaluated in a mouse microvasculature perfusion model and a new mouse model of endocarditis.Results. Contrary to other coagulase-negative staphylococci, S. lugdunensis bound to VWF under flow, thus enabling its adhesion to endothelial cells and to the subendothelial matrix. In inflamed vessels of the mesenteric circulation, VWF recruited S. lugdunensis to the vessel wall. In a novel endocarditis mouse model, local inflammation and the resulting release of VWF enabled S. lugdunensis to bind and colonize the heart valves.Conclusions. S. lugdunensis binds directly to VWF, which proved to be vital for withstanding shear forces and for its adhesion to the vessel wall and cardiac valves. This mechanism explains why S. lugdunensis causes more-aggressive infections, including endocarditis, compared with other coagulase-negative staphylococci.