Dequalinium chloride promotes the killing efficacy of aminoglycoside antibiotics against Pseudomonas aeruginosa by enhancing membrane potential

ABSTRACT Dequalinium chloride is a dicationic amphiphilic quaternary ammonium compound that is used as an anti-infective drug. Here, we found that it potentiates bactericidal efficacies of aminoglycoside antibiotics against Pseudomonas aeruginosa . Dequalinium chloride increases respiratory activity and bacterial membrane potential, thereby promoting intracellular uptake of aminoglycosides. Furthermore, the dequalinium chloride–amikacin combination demonstrated a synergistic bactericidal effect in a murine acute pneumonia model, indicating its therapeutic potential. IMPORTANCE Antimicrobial resistance (AMR) poses a severe global health threat. Novel antibiotics and therapeutic strategies are urgently needed. This study revealed that dequalinium chloride (DC) synergizes with aminoglycosides against planktonic and biofilm-associated P. aeruginosa , which is an important pathogen. Mechanistic study reveals that DC enhances bacterial respiration and membrane potential to promote aminoglycosides uptake. The DC–amikacin combination is effective in a murine pneumonia model. These findings provide a promising therapeutic strategy for combating P. aeruginosa infections.