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Incorporating Single-Copper Sites and Host Defense Peptides into a Nanoreactor for Antibacterial Therapy by Bioinspired Design
Engineering ( IF 10.1 ) Pub Date : 2024-10-22 , DOI: 10.1016/j.eng.2024.09.021
Xuan Chen, Wei Luo, Qun Gao, Congrong Chen, Lichan Li, Dongbo Liu, Shaoyun Wang

A sustainable solution to the dramatic spread of antibiotic resistance threatening public health security is the development of antibiotic-free antimicrobial substances. Inspired by natural host defense mechanisms involving amino-terminal copper–nickel binding motif (ATCUN) antimicrobial peptides (AMPs), we have designed and prepared an artificial complex (Cu@G-AMPs) incorporating single-atom Cu catalysts for antibacterial therapy. The substrate of the complex, formed from guanine doped with abundant heteroatoms, anchored single Cu atoms with a coordination number of 2 and an average bond length of 1.91 Å. Interestingly, Cu@G-AMPs, exhibiting Fenton-like catalytic activity, caused the inactivation of methicillin-resistant Staphylococcus aureus (MRSA) by generating and delivering reactive oxygen species (ROS) cargo. Mechanistically, the intrinsic stress response system of MRSA underwent an irreversible collapse when Cu@G-AMPs initiated its offensive program associated with non-specific targets. Furthermore, Cu@G-AMPs, which inherited the immunomodulatory properties of AMPs, sequentially carried out the functions of pulling edge closure, stabilizing granulation tissue, promoting collagen fiber proliferation, alleviating inflammation, and promoting neovascularization in wound areas infected by MRSA. Our results show that Cu@G-AMPs will provide a new perspective on untangling the complex regulatory networks that resistant bacteria have cultivated to deactivate commercial antibiotics.

中文翻译:


通过 Bioinspired Design 将单铜位点和宿主防御肽整合到纳米反应器中用于抗菌治疗



对于威胁公共卫生安全的抗生素耐药性急剧蔓延,一个可持续的解决方案是开发不含抗生素的抗菌物质。受涉及氨基末端铜镍结合基序 (ATCUN) 抗菌肽 (AMP) 的天然宿主防御机制的启发,我们设计并制备了一种人工复合物 (Cu@G-AMPs),其中包含用于抗菌治疗的单原子 Cu 催化剂。该复合物的底物由掺杂了丰富的杂原子的鸟嘌呤形成,锚定了配位数为 2、平均键长为 1.91 Å 的单个 Cu 原子。有趣的是,表现出 Fenton 样催化活性的 Cu@G-AMPs 通过产生和输送活性氧 (ROS) 货物导致耐甲氧西林金黄色葡萄球菌 (MRSA) 失活。从机制上讲,当 MRSA 启动与非特异性目标相关的攻击性计划时,Cu@G-AMP 的内在应激反应系统发生了不可逆转的崩溃。此外,继承了 AMPs 免疫调节特性的 Cu@G-AMPs 依次在受 MRSA 感染的伤口区域执行拉边闭合、稳定肉芽组织、促进胶原纤维增殖、缓解炎症和促进新生血管形成的功能。我们的结果表明,Cu@G-AMPs 将为解开耐药细菌培养的复杂调控网络以提供新的视角,以使商业抗生素失活。
更新日期:2024-10-22
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