A Dual-Functional Biohybrid Nanorobot to Synergistically Eradicate Biofilm and Degrade Antibiotic Resistance Genes

Abstract

The environmental dissemination of antibiotic-resistant bacteria and associated resistance genes poses a serious threat to public health and ecological safety, while persistent biofilms serve as reservoirs and transmission hubs for antibiotic resistance genes (ARGs). Current strategies are unable to synergistically eradicate biofilm and degrade ARGs. Here, we developed a dual-functional biohybrid nanorobot that integrates the lytic bacteriophage (N4) with Pd nanozymes to eradicate multidrug-resistant Escherichia coli NDM-1 biofilms and degrade released ARGs. Phage N4 enables targeted bacterial lysis and precise delivery of Pd nanozymes, which catalyze the production of reactive oxygen species to enhance antibacterial activity, disrupt biofilm structure, and degrade liberated plasmid-encoded blaNDM-1 genes. This N4@Pd nanorobot achieves over 95% biofilm removal and approximately 2.78 log10 reduction in ARGs. Transcriptomic analyses reveal that the nanorobot treatment inhibits core bacterial metabolic pathways and key regulators of biofilm maintenance. In simulated wastewater, the nanorobot maintains over 90% biofilm removal and approximately 2.06 log10 reduction in ARGs, underscoring its potential in environmental water treatment. This study presents a promising strategy to counteract the spread of antibiotic resistance through integrated biofilm disruption and genetic decontamination.