Self-assembly nanostructured polysulfoniums as antimicrobial potentiator targeted bacterial membrane reversing antimicrobial resistance.

Antimicrobial resistance (AMR) poses a critical public health threat, primarily driven by the misuse and overuse of antimicrobials in both veterinary and public healthcare systems. In the face of accelerating AMR and a dwindling antibiotic pipeline, the strategic deployment of adjuvant therapies presents a promising approach to potentiate current antibiotics and combat resistant pathogens. Herein, we designed a series of sulfur-based cationic polymers polysulfoniums to obtain a potential antimicrobial adjuvant tackling AMR infections. These polysulfoniums presented effective activity against Gram-positive and Gram-negative bacteria with minimum inhibition concentrations (MICs) of 2 μg/mL. Furthermore, polysulfoniums can completely eradicate bacteria under both aerobic and anaerobic conditions within 2 h. In-depth mechanistic studies revealed that polysulfoniums exhibited bactericidal activities by disrupting outer membrane and the redox balance. Moreover, polysulfoniums helped antimicrobial to enter the bacterial cytoplasm, and the combination of 1,10-PS+ with antimicrobial agent including gentamicin, florfenicol, and ciprofloxacin were an efficient approach to eliminate the bacteria and restored the antimicrobial effectiveness. Additionally, the combination of 1,10-PS+ and ciprofloxacin exhibited robust bactericidal effects, effectively reducing Salmonella colonization in vivo. Overall, this research shed new light on polysulfoniums as antibacterial potentiator, offering viable strategies to restore antimicrobial sensitivity and enable environmentally sustainable clinical applications.