Antibacterial activity and mechanism of naphthoquine phosphate against ceftazidime-resistant Acinetobacter baumannii via cell membrane disruption and ROS induction

NQP exhibited broad-spectrum antibacterial activity, with a MIC of 62.5 μg/mL against <i>Acinetobacter baumannii</i> LAC-4. Its inhibition kinetics curve confirmed a concentration-dependent inhibitory effect. Membrane permeability tests revealed that NQP disrupts cell membrane integrity, enhancing permeability-consistent with TEM/SEM observations showing significant structural damage in NQP-treated <i>A. baumannii</i>, including membrane rupture, cellular deformation, and cytoplasmic disorganization. Oxidative damage tests indicated NQP impacts bacterial metabolism, and transcriptome analysis further demonstrated that NQP disrupts multiple physiological pathways, primarily through enhanced membrane permeability and induced oxidative stress. These findings support NQP as a promising molecular scaffold for developing novel therapies against <i>Acinetobacter baumannii</i> infections, highlighting its potential in drug repurposing strategies for combating drug resistance.