Artificial Phages with Biocatalytic Spikes for Synergistically Eradicating Antibiotic-Resistant Biofilms.
Sutong XiaoLan XieYang GaoMao WangWei GengXizheng WuRaul D RodriguezLiang ChengLi QiuChong ChengPublished in: Advanced materials (Deerfield Beach, Fla.) (2024)
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, we propose the de novo design of a spiky Ir@Co 3 O 4 particle 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. Our in vivo results demonstrate that the artificial phage can treat the biofilm-induced recalcitrant infected wounds equivalent to vancomycin. We suggest 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 non-antibiotic disinfection. This article is protected by copyright. All rights reserved.
Keyphrases
- pseudomonas aeruginosa
- candida albicans
- staphylococcus aureus
- biofilm formation
- public health
- reactive oxygen species
- cystic fibrosis
- high glucose
- dna damage
- cell death
- mass spectrometry
- methicillin resistant staphylococcus aureus
- diabetic rats
- drug delivery
- oxidative stress
- dna methylation
- endothelial cells
- helicobacter pylori
- transcription factor
- genome wide identification
- bioinformatics analysis
- cell wall