Department of Precision Medicine, Institute for Antimicrobial Resistance Research and Therapeutics, Graduate School of Basic Medical Sciences (GSBMS), Sungkyunkwan University School of Medicine, Suwon, 16419, South Korea.
Institute of Microbiology, University of Agriculture, Faisalabad, 38000, Pakistan.
Small. 2021 May;17(20):e2100257. doi: 10.1002/smll.202100257. Epub 2021 Apr 10.
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.
耐甲氧西林金黄色葡萄球菌（MRSA）可引起从皮肤感染到致命性败血症等多种疾病，由于其具有多重耐药性（MDR），已成为人类健康的严重威胁。因此，需要一种无耐药性的抗菌治疗方法来克服 MDR-MRSA 感染。在本研究中，开发了一种抗菌纳米机器人（Ab-nanobot），其中细胞壁结合结构域（CBD）-内溶素作为传感器，与由氧化铁/二氧化硅核壳组成的执行器共价连接。CBD-内溶素传感器表现出优异的特异性，可检测、结合和积累在金黄色葡萄球菌 USA300 细胞表面，即使在细菌混合物和宿主细胞感染中也是如此。Ab-nanobot 可特异性捕获和杀死 MRSA，以响应医学上认可的射频（RF）电磁刺激（EMS）信号。当 Ab-nanobot 在细胞表面接收到 RF-EMS 信号时，执行器通过产生局部热量和活性氧物种来破坏细胞壁，在 20 分钟内将 MRSA 的细胞死亡率提高到 99.999%。通过小鼠皮下皮肤感染模型证明了 Ab-nanobot 的体内疗效。总之，本研究通过提供针对金黄色葡萄球菌的高度特异性纳米机器人，为克服 MDR-MRSA 感染提供了一种无耐药性的纳米医学策略。
