An innate immune system intricately leverages unique mechanisms to inhibit colonization of external invasive Bacteria, for example human defensin-6, through responsive encapsulation of bacteria. Infection and accompanying antibiotic resistance stemming from Gram-negative bacteria aggregation represent an emerging public health crisis, which calls for research into novel anti-bacterial therapeutics. Herein, inspired by naturally found host-defense peptides, we design a defensin-like peptide ligand, bacteria extracellular trap (BET) peptide, with modular design composed of targeting, assembly, and hydrophobic motifs with an aggregation-induced emission feature. The ligand specifically recognizes Gram-negative bacteria via targeting cell wall conserved lipopolysaccharides (LPS) and transforms from nanoparticles to nanofibrous networks in situ to trap bacteria and induce aggregation. Importantly, treatment of the BET peptide was found to have an antibacterial effect on the Pseudomonas aeruginosa strain, which is comparable to neomycin. Animal studies further demonstrate its ability to trigger aggregation of bacteria in vivo. This biomimetic self-assembling BET peptide provides a novel approach to fight against pathogenic Gram-negative bacteria.

中文翻译：

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肽选择性识别革兰氏阴性细菌并通过界面自组装形成细菌胞外陷阱（BET）

先天免疫系统错综复杂地利用独特的机制，通过细菌的响应性封装来抑制外部侵入性细菌（例如人防御素 6）的定植。革兰氏阴性菌聚集引起的感染和随之而来的抗生素耐药性代表了一场新出现的公共卫生危机，需要研究新型抗菌疗法。在此，受天然发现的宿主防御肽的启发，我们设计了一种防御素样肽配体，即细菌胞外捕获（BET）肽，其模块化设计由靶向、组装和具有聚集诱导发射特征的疏水基序组成。该配体通过靶向细胞壁保守的脂多糖（LPS）特异性识别革兰氏阴性细菌，并原位从纳米颗粒转变为纳米纤维网络以捕获细菌并诱导聚集。重要的是，BET肽的处理被发现对铜绿假单胞菌菌株具有与新霉素相当的抗菌作用。动物研究进一步证明其能够引发体内细菌聚集。这种仿生自组装BET肽提供了一种对抗致病性革兰氏阴性菌的新方法。