Polymorphisms in fibronectin binding protein A of Staphylococcus aureus are associated with infection of cardiovascular devices
Polymorphisms in fibronectin binding protein A of Staphylococcus aureus are associated with infection of cardiovascular devices
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DOI：
10.1073/pnas.1109071108
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发表时间：
2011-11-08
影响因子：
11.1
通讯作者：
Fowler, Vance G., Jr.
中科院分区：
文献类型：
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作者：
Lower, Steven K.;Lamlertthon, Supaporn;Fowler, Vance G., Jr.
医疗植入物，如心血管设备，提高了无数人的生活质量，但可能会感染金黄色葡萄球菌等细菌。这种感染以生物膜的形式出现，生物膜是附着在固体基质表面的细菌细胞的结构化群落。每一个生物膜都始于细菌和基质之间的吸引力或结合。我们使用原子力显微镜来实验性地探测纤连蛋白涂覆的表面（即，代表植入的心脏装置）和来自80个临床分离的S.金黄色。这些分离株来源于植入受感染心脏器械（CDI; n = 26）、未感染心脏器械（n = 20）和无症状受试者（n = 34）的前鼻孔。CDI分离株表现出独特的结合力签名，并在纤连蛋白结合蛋白A中具有对应于E652 D，H782 Q和K786 N的特定单氨基酸多态性。在计算机分子动力学模拟表明，残基D 652，Q782，和N786纤连蛋白结合蛋白A形成额外的氢键与纤连蛋白，补充较高的结合力和能量的原子力显微镜测量的CDI分离。这项研究意义重大，因为它将病原菌生物膜从作用于纳米尺度空间的键的长度尺度与人类疾病的临床表现联系起来。
Medical implants, like cardiovascular devices, improve the quality of life for countless individuals but may become infected with bacteria like Staphylococcus aureus. Such infections take the form of a biofilm, a structured community of bacterial cells adherent to the surface of a solid substrate. Every biofilm begins with an attractive force or bond between bacterium and substratum. We used atomic force microscopy to probe experimentally forces between a fibronectin-coated surface (i.e., proxy for an implanted cardiac device) and fibronectin-binding receptors on the surface of individual living bacteria from each of 80 clinical isolates of S. aureus. These isolates originated from humans with infected cardiac devices (CDI; n = 26), uninfected cardiac devices (n = 20), and the anterior nares of asymptomatic subjects (n = 34). CDI isolates exhibited a distinct binding-force signature and had specific single amino acid polymorphisms in fibronectin-binding protein A corresponding to E652D, H782Q, and K786N. In silico molecular dynamics simulations demonstrate that residues D652, Q782, and N786 in fibronectin-binding protein A form extra hydrogen bonds with fibronectin, complementing the higher binding force and energy measured by atomic force microscopy for the CDI isolates. This study is significant, because it links pathogenic bacteria biofilms from the length scale of bonds acting across a nanometer-scale space to the clinical presentation of disease at the human dimension.