Staphylococcus aureus clumping factor A is a force-sensitive molecular switch that activates bacterial adhesion.
Staphylococcus aureus clumping factor A is a force-sensitive molecular switch that activates bacterial adhesion.
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金黄色葡萄球菌块状因子A是一种激活细菌粘附力的力敏感分子开关。
DOI：
10.1073/pnas.1718104115
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发表时间：
2018-05-22
影响因子：
11.1
通讯作者：
Dufrêne YF
中科院分区：
文献类型：
--
作者：
Herman-Bausier P;Labate C;Towell AM;Derclaye S;Geoghegan JA;Dufrêne YF
金黄色葡萄球菌表面蛋白凝集因子A（ClfA）通过分子相互作用与血浆蛋白纤维蛋白原（Fg）结合，但对其了解甚少。在这里，我们解开的力量指导ClfA和固定化Fg之间的相互作用，表明它是显着增强拉伸负荷。我们的研究结果有利于ClfA通过两个不同的结合位点与Fg相互作用的模型，其粘附功能受到机械力的严格调节。这种力增强的粘附力解释了ClfA促进S的能力，这让人想起了捕获键机制。金黄色葡萄球菌定植宿主组织和生物医学设备在物理应力。成簇因子A（ClfA）是金黄色葡萄球菌的一种细胞壁锚定蛋白，是各种感染中的毒力因子，有助于蛋白质包被生物材料的定殖。ClfA通过迄今为止尚未研究的分子力促进细菌粘附到血浆蛋白纤维蛋白原（Fg）。ClfA的一个独特但知之甚少的特征是其在高剪切应力下有利于粘附至Fg的能力。揭示ClfA-Fg相互作用的强度和动力学将有助于我们更好地理解S。金黄色葡萄球菌定殖于植入的装置并承受生理剪切应力。通过单分子实验，我们表明，ClfA的行为作为一个力敏感的分子开关，增强葡萄球菌粘附在机械应力下。ClfA和固定化Fg之间的键在低张力下是弱的（约0.1 nN），但通过机械张力显著增强（约1.5 nN），如用捕获键所观察到的。模拟Fg γ链C端片段的肽可抑制强键，但不抑制弱键。这些结果表明，ClfA通过两个不同的结合位点与Fg相互作用的模型，其粘附功能由机械张力调节。这种力激活机制具有生物学意义，因为它在分子水平上解释了ClfA在高生理剪切应力下促进细菌附着的能力。
The Staphylococcus aureus surface protein clumping factor A (ClfA) binds to the blood plasma protein fibrinogen (Fg) via molecular interactions that are poorly understood. Here, we unravel the forces guiding the interaction between ClfA and immobilized Fg, showing that it is dramatically enhanced by tensile loading. Our findings favor a model whereby ClfA interacts with Fg via two distinct binding sites, the adhesive function of which is tightly regulated by mechanical force. Reminiscent of a catch bond mechanism, this force-enhanced adhesion explains the ability of ClfA to promote S. aureus colonization of host tissues and biomedical devices under physical stress. 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.
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DOI：
10.1038/nrmicro3432
发表时间：
2015-05
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Flores-Mireles AL;Walker JN;Caparon M;Hultgren SJ
通讯作者：
Hultgren SJ
影响因子：
6.7
作者：
Ganesh VK;Rivera JJ;Smeds E;Ko YP;Bowden MG;Wann ER;Gurusiddappa S;Fitzgerald JR;Höök M
通讯作者：
Höök M
影响因子：
14.8
作者：
Beaussart, Audrey;El-Kirat-Chatel, Sofiane;Dufrene, Yves F.
通讯作者：
Dufrene, Yves F.
机械强度和抑制金黄色葡萄球菌胶原蛋白结合蛋白CNA。
影响因子：
6.4
作者：
Herman-Bausier P;Valotteau C;Pietrocola G;Rindi S;Alsteens D;Foster TJ;Speziale P;Dufrêne YF
通讯作者：
Dufrêne YF
DOI：
10.1161/atvbaha.107.152058
发表时间：
2008-02-01
影响因子：
8.7
作者：
Kerrigan, Steven W.;Clarke, Niamh;Cox, Dermot
通讯作者：
Cox, Dermot