文章基本信息

标题：Staphylococcus aureus clumping factor A is a force-sensitive molecular switch that activates bacterial adhesion
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作者：Philippe Herman-Bausier ; Cristina Labate ; Aisling M. Towell 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2018
卷号：115
期号：21
页码：5564-5569
DOI：10.1073/pnas.1718104115
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Clumping factor A (ClfA), a cell-wall–anchored protein from Staphylococcus aureus , is a virulence factor in various infections and facilitates the colonization of protein-coated biomaterials. ClfA promotes bacterial adhesion to the blood plasma protein fibrinogen (Fg) via molecular forces that have not been studied so far. A unique, yet poorly understood, feature of ClfA is its ability to favor adhesion to Fg at high shear stress. Unraveling the strength and dynamics of the ClfA–Fg interaction would help us better understand how S. aureus colonizes implanted devices and withstands physiological shear stress. By means of single-molecule experiments, we show that ClfA behaves as a force-sensitive molecular switch that potentiates staphylococcal adhesion under mechanical stress. The bond between ClfA and immobilized Fg is weak (∼0.1 nN) at low tensile force, but is dramatically enhanced (∼1.5 nN) by mechanical tension, as observed with catch bonds. Strong bonds, but not weak ones, are inhibited by a peptide mimicking the C-terminal segment of the Fg γ-chain. These results point to a model whereby ClfA interacts with Fg via two distinct binding sites, the adhesive function of which is regulated by mechanical tension. This force-activated mechanism is of biological significance because it explains at the molecular level the ability of ClfA to promote bacterial attachment under high physiological shear stress.
关键词：Staphylococcus aureus ; ClfA ; fibrinogen ; shear stress ; atomic force microscopy