Key Laboratory of Catalysis and Energy Materials Chemistry of Ministry of Education and Hubei Key Laboratory of Catalysis and Materials Science, South-Central University for Nationalities, 182 Minzu Road, Hongshan District, Wuhan, Hubei 430074, P.R. China.
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, Haidian District, Beijing 100190, P.R. China.
Sci Adv. 2020 May 8;6(19):eaaz4767. doi: 10.1126/sciadv.aaz4767. eCollection 2020 May.
Using broad-spectrum antibiotics for microbial infection may cause flora disequilibrium, drug-resistance, etc., seriously threatening human health. Here, we design a human defensin-6 mimic peptide (HDMP) that inhibits bacterial invasion in vivo through mimicking the mechanisms of human defensin-6 with high efficiency and precision. The HDMP with ligand and self-assembling peptide sequence recognizes bacteria through ligand-receptor interactions and subsequently traps bacteria by an in situ adaptive self-assembly process and resulting nanofibrous networks; these trapped bacteria are unable to invade host cells. In four animal infection models, the infection rate was markedly decreased. Notably, administration of HDMP (5 mg/kg) nanoparticles increased the survival rate of mice with methicillin-resistant bacteremia by as much as 100%, even more than that of vancomycin treatment (5 mg/kg, 83.3%)-treated group, the golden standard of antibiotics. This biomimetic peptide shows great potential as a precise and highly efficient antimicrobial agent.
广谱抗生素用于治疗微生物感染可能会导致菌群失调、耐药性等问题，严重威胁人类健康。在这里，我们设计了一种人防御素-6 模拟肽 (HDMP)，它通过高效和精确地模拟人防御素-6 的机制来抑制体内细菌的入侵。具有配体和自组装肽序列的 HDMP 通过配体-受体相互作用识别细菌，然后通过原位自适应自组装过程和由此产生的纳米纤维网络捕获细菌；这些被捕获的细菌无法入侵宿主细胞。在四个动物感染模型中，感染率明显降低。值得注意的是，给予 5mg/kg 的 HDMP 纳米粒可使耐甲氧西林金黄色葡萄球菌菌血症小鼠的存活率提高 100%，甚至高于抗生素的金标准万古霉素（5mg/kg，83.3%）治疗组。这种仿生肽作为一种精确高效的抗菌剂具有巨大的潜力。
