Killing of colistin-resistant Aeromonas hydrophila by a synthetic peptide

Multi-drug-resistant Aeromonas hydrophila infections are becoming increasingly threatening, and the development of novel antimicrobial drugs is indispensable. Herein, we demonstrate that this novel peptide is highly active against colistin-resistant A. hydrophila strain and shows sustained killing efficacy in vivo. Mechanistic studies showed that D-Q7 interacted with phosphatidylglycerol and lipopolysaccharide in the bacterial cell membrane, with an increase in intracellular ROS as well as a decrease in ATP level, ultimately leading to cell membrane disruption and bacterial death. Importantly, our study identified gene3832 as a potential regulator of membrane permeability, which may act as a potential modulator of bacterial susceptibility to D-Q7. The role of gene3832 was further confirmed by gene knockout and complementation assays. Consistently, we observed that gene3832 was also involved in biofilm formation in the colistin-resistant A. hydrophila strain. Collectively, our study provides an effective antimicrobial strategy with potential targets for the treatment of drug-resistant A. hydrophila infection.