A Strategy of Killing Two Birds With One Stone for Blocking Drug Resistance Spread With Engineered Bdellovibrio bacteriovorus

Abstract

AbstractDrug‐resistant pathogens significantly threaten human health and life. Simply killing drug‐resistant pathogens cannot effectively eliminate their threat since the drug‐resistant genes (DRGs) released from dead drug‐resistant pathogens are difficult to eliminate and can further spread via horizontal gene transfer, leading to the spread of drug resistance. The development of antibacterial materials with sterilization and DRGs cleavage activities is highly crucial. Herein, a living system, Ce‐PEA@Bdello, is fabricated with bacterial killing and DRGs cleavage activities for blocking bacterial drug resistance dissemination by engineered Bdellovibrio bacteriovorus (Bdello). Ce‐PEA@Bdello is obtained by engineering Bdello with dopamine and a multinuclear cerium (IV) complex. Ce‐PEA@Bdello can penetrate and eliminate kanamycin‐resistant P. aeruginosa (KanR) biofilms via the synergistic effect of predatory Bdello and photothermal polydopamine under near‐infrared light. Additionally, the DNase‐mimicking ability of Ce‐PEA@Bdello endows it with genome and plasmid DNA cleavage ability. An in vivo study reveals that Ce‐PEA@Bdello can eliminate P. aeruginosa (KanR) and cleave DRGs in scald/burn infected wounds to block the spread of drug resistance and accelerate wound healing. This bioactive system constructed from natural living materials offers a promising means for blocking the spread of drug resistance.