CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, P.R. China.
Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, P.R. China.
J Mater Chem B. 2024 Apr 17;12(15):3676-3685. doi: 10.1039/d3tb02559d.
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 targeting cell wall conserved lipopolysaccharides (LPS) and transforms from nanoparticles to nanofibrous networks to trap bacteria and induce aggregation. Importantly, treatment of the BET peptide was found to have an antibacterial effect on the strain, which is comparable to neomycin. Animal studies further demonstrate its ability to trigger aggregation of bacteria . This biomimetic self-assembling BET peptide provides a novel approach to fight against pathogenic Gram-negative bacteria.
先天免疫系统巧妙地利用独特的机制来抑制外部入侵细菌的定植，例如人类防御素-6，通过对细菌的响应性包裹。源自革兰氏阴性菌聚集的感染和随之而来的抗生素耐药性是当前公共卫生领域面临的一项新挑战，这就需要研究新的抗菌治疗方法。受天然存在的宿主防御肽的启发，我们设计了一种防御素样肽配体，即细菌细胞外陷阱 (BET) 肽，其采用模块化设计，由靶向、组装和疏水性基序组成，并具有聚集诱导发射特性。该配体特异性识别革兰氏阴性菌，靶向细胞壁保守的脂多糖 (LPS)，并从纳米颗粒转变为纳米纤维网络，从而捕获细菌并诱导其聚集。重要的是，BET 肽的治疗作用被发现对该菌株具有抗菌作用，与新霉素相当。动物研究进一步证明了其诱导细菌聚集的能力。这种仿生自组装的 BET 肽为对抗致病性革兰氏阴性菌提供了一种新方法。
