Targeted Recognition, Fluorescent Tracking and Augmented Killing of Multi-Bacterial Infection via Synergizing Magnetic Bead-Armored Phage Cocktail with Enzyme-Activated AIE Probes

Abstract

Accurate identification and elimination of multi-bacterial infections are critical due to their significant threat to human health, the complexity of synergistic pathogenic mechanisms and their pivotal role in accelerating antibiotic resistance. Here, we developed a multiplex phage-based fluorescence assay using encoded magnetic nanobeads and multifunctional alkaline phosphatase (ALP)-activatable aggregation-induced emission (AIE) probes for synchronously sensitive detection and efficient elimination of multiple pathogenic bacteria. Preselected phages were covalently conjugated to magnetic nanobeads to form phage cocktail recipe, enabling specific and precise separation of target bacteria from mixed samples. The high expression of ALP within bacteria triggers enzymatic cleavage of AIE probes, forming luminescent aggregates for sensitive detection, while quinone methide species generated in situ exhibit strong chemodynamic and photodynamic activities for enhanced bacterial killing. Combining the inherent bacteriolytic activity of phages on magnetic nanobeads, significantly boosted efficacy in killing multi-bacterial infections was achieved. Both in vitro and in vivo experiments demonstrated that this integrated system enables sensitive identification of multi-bacterial infections and augmented antibacterial efficiency, offering a novel strategy for the real-time, precise diagnosis and treatment of multi-bacterial infections.