抗生素耐药病原体已成为全球公共卫生危机,尤其是生物膜诱导的难治性感染。高效,安全,迫切需要生物膜微环境(BME)适应性治疗策略来对抗抗生素抗性生物膜。这里,受噬菌体迷人的生物结构和功能的启发,我们建议从头设计尖刺的Ir@Co3O4颗粒,以用作人工噬菌体,以协同根除耐抗生素的金黄色葡萄球菌生物膜。受益于丰富的纳米尖峰和高活性的Ir位点,合成的人工噬菌体可以同时实现高效的生物膜积累,胞外聚合物(EPS)渗透,和优越的BME适应性活性氧(ROS)生成,从而促进原位ROS递送并增强生物膜根除。此外,代谢组学发现,人工噬菌体阻碍细菌与EPS的附着,破坏了BME的维护,并通过下调相关基因来促进生物膜的分散和根除,以进行内部和细胞外环境的生物合成和保存。我们的体内结果表明,人工噬菌体可以治疗与万古霉素相当的生物膜诱导的顽固感染伤口。我们建议,这种具有协同“渗透和根除”能力的尖刺人工噬菌体的设计为仿生和非抗生素消毒提供了一条新途径。本文受版权保护。保留所有权利。
Antibiotic-resistant pathogens have become a global public health crisis, especially biofilm-induced refractory infections. Efficient, safe, and biofilm microenvironment (BME)-adaptive therapeutic strategies are urgently demanded to combat antibiotic-resistant biofilms. Here, inspired by the fascinating biological structures and functions of phages, the de novo design of a spiky Ir@Co3O4 particle is proposed to serve as an artificial phage for synergistically eradicating antibiotic-resistant Staphylococcus aureus biofilms. Benefiting from the abundant nanospikes and highly active Ir sites, the synthesized artificial phage can simultaneously achieve efficient biofilm accumulation, extracellular polymeric substance (EPS) penetration, and superior BME-adaptive reactive oxygen species (ROS) generation, thus facilitating the in situ ROS delivery and enhancing the biofilm eradication. Moreover, metabolomics found that the artificial phage obstructs the bacterial attachment to EPS, disrupts the maintenance of the BME, and fosters the dispersion and eradication of biofilms by down-regulating the associated genes for the biosynthesis and preservation of both intra- and extracellular environments. The in vivo results demonstrate that the artificial phage can treat the biofilm-induced recalcitrant infected wounds equivalent to vancomycin. It is suggested that the design of this spiky artificial phage with synergistic \"penetrate and eradicate\" capability to treat antibiotic-resistant biofilms offers a new pathway for bionic and nonantibiotic disinfection.