Interrupting Antibiotic Resistance Transmission via Natural Product-Embedded Lipopeptide–Polymeric Nanoblockers

Recent antimicrobial advancements highlight the pivotal role of antibiotic resistance transmission in aggravating drug-resistant bacterial infections. Inhibiting the spread of antibiotic resistance remains a significant challenge, particularly in the treatment of human infections. In this study, we developed virus-inspired lipopeptide–polymeric nanoblockers to impede transmission of antibiotic resistance from donor antibiotic-resistant bacteria to recipient bacteria. Berberine-encapsulated lipopeptide–polymeric nanoparticles (B-LPNs) effectively internalize into drug-resistant bacteria, mimic viral infection, deliver natural products, and block the spread of resistant plasmids. Our findings visually demonstrated that pretreating donor bacteria with B-LPNs preserved the antibiotic sensitivity of recipient bacteria and suppressed their growth at the minimum inhibitory concentration. In vivo antibacterial assessments further confirmed the efficacy of B-LPNs in halting antibiotic resistance transmission among Gram-negative bacteria along with satisfactory biocompatibility. This work introduces a novel nanomaterial-based strategy to address the challenges of antibiotic resistance transmission, offering safe, efficient, and clinically promising nanoblockers.