Biomimetic metal-drug coordination nanoplatform to counteract drug resistance in Pseudomonas aeruginosa via energy disruption

Antibiotic resistance in Pseudomonas aeruginosa reduces treatment efficacy and poses a serious threat to clinical therapy. This study demonstrates that a pH-responsive biomimetic nanoplatform, designated Ce-Car@EV, can reverse antibiotic resistance by depleting intracellular ATP and inhibiting efflux pumps. The platform significantly reduced bacterial loads in the lungs and systemic organs, extended circulation time through immune evasion, downregulated efflux pump-related genes, downregulated key oxidative phosphorylation genes, and inhibited tricarboxylic acid (TCA) cycle enzymes. By disrupting the proton motive force and inhibiting antibiotic efflux, Ce-Car@EV restored antibiotic sensitivity and alleviated lung damage in a mouse model.