Methicillin-resistant Staphylococcus aureus (MRSA) causes diseases ranging from skin infections to lethal sepsis and has become a serious threat to human health due to multiple-drug resistance (MDR). Therefore, a resistance-free antibacterial therapy is necessary to overcome MDR MRSA infections. In this study, an antibacterial nanorobot (Ab-nanobot) is developed wherein a cell wall-binding domain (CBD)-endolysin, acting as a sensor, is covalently conjugated with an actuator consisting of an iron oxide/silica core–shell. The CBD-endolysin sensor shows an excellent specificity to detect, bind, and accumulate on the S. aureus USA300 cell surface even in a bacterial consortium, and in host cell infections. Ab-nanobot specifically captures and kills MRSA in response to medically approved radiofrequency (RF) electromagnetic stimulation (EMS) signal. When Ab-nanobot receives the RF-EMS signal on the cell surface, actuator induces cell death in MRSA with 99.999% removal within 20 min by cell-wall damage via generation of localized heat and reactive oxygen species. The in vivo efficacy of Ab-nanobot is proven using a mice subcutaneous skin infection model. Collectively, this study offers a nanomedical resistance-free strategy to overcome MDR MRSA infections by providing a highly specific nanorobot for S. aureus.

中文翻译：

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一种用于特异性靶向和去除多重耐药金黄色葡萄球菌的抗菌纳米机器人方法

耐甲氧西林金黄色葡萄球菌(MRSA) 会引起从皮肤感染到致命性败血症的各种疾病，并且由于多重耐药性 (MDR) 已成为对人类健康的严重威胁。因此，需要一种无耐药性的抗菌疗法来克​​服 MDR MRSA 感染。在这项研究中，开发了一种抗菌纳米机器人（Ab-nanobot），其中作为传感器的细胞壁结合域（CBD）-内溶素与由氧化铁/二氧化硅核-壳组成的致动器共价结合。CBD-内溶素传感器在检测、结合和积累金黄色葡萄球菌方面表现出极好的特异性即使在细菌聚生体和宿主细胞感染中，USA300 细胞表面也是如此。Ab-nanobot 响应医学认可的射频 (RF) 电磁刺激 (EMS) 信号，专门捕获并杀死 MRSA。当 Ab-nanobot 在细胞表面接收到 RF-EMS 信号时，致动器通过产生局部热量和活性氧，通过细胞壁损伤在 20 分钟内诱导 MRSA 中的细胞死亡，去除率达 99.999%。使用小鼠皮下皮肤感染模型证明了 Ab-nanobot 的体内功效。总的来说，这项研究提供了一种无纳米医学耐药性的策略，通过为金黄色葡萄球菌提供高度特异性的纳米机器人来克服 MDR MRSA 感染。