超级细菌耐药模型中粘附分子-粘肽结合的纳米机械检测
Nanomechanical detection of antibiotic-mucopeptide binding in a model for superbug drug resistance
摘要：
耐药性超级细菌耐甲氧西林金黄色葡萄球菌（MRSA）和耐万古霉素肠球菌（VRE）的惊人增长正在推动新技术的发展，以研究抗生素及其作用方式。我们报告了万古霉素结合细菌细胞壁前体类似物（粘肽）的悬臂阵列上的无标记检测，灵敏度为10 nM，血清中的临床相关浓度。差分测量定量万古霉素敏感和万古霉素耐药粘肽类似物的结合常数。此外，通过系统地修改粘肽密度，我们获得了新的见解的起源表面应力。我们建议，应力是一个产品的局部化学结合因子和几何因子描述的机械连接的区域受局部结合的渗滤过程。我们的发现将BioMEMS器件置于一类新的并行系统中。渗滤概念将支持设备和涂层的设计，以显着降低药物检测限，也可能影响我们对细菌中抗生素药物作用的理解。
英文摘要：
The alarming growth of the antibiotic-resistant superbugs methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) is driving the development of new technologies to investigate antibiotics and their modes of action. We report the label-free detection of vancomycin binding to bacterial cell wall precursor analogues (mucopeptides) on cantilever arrays, with 10 nM sensitivity and at clinically relevant concentrations in blood serum. Differential measurements quantified binding constants for vancomycin-sensitive and vancomycin-resistant mucopeptide analogues. Moreover, by systematically modifying the mucopeptide density we gain new insights into the origin of surface stress. We propose that stress is a product of a local chemical binding factor and a geometrical factor describing the mechanical connectivity of regions affected by local binding in terms of a percolation process. Our findings place BioMEMS devices in a new class of percolative systems. The percolation concept will underpin the design of devices and coatings to significantly lower the drug detection limit and may also impact on our understanding of antibiotic drug action in bacteria.
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