Licochalcone A alleviates the pathogenicity of Aeromonas hydrophila by affecting the function of aerolysin

Proteins in aquatic products satisfy the increasing demand of high-quality proteins of humans, resulting in a rapid development of freshwater aquaculture. However, bacterial diseases in aquatic animals often cause economic losses worldwide. Antibiotics are frequently used in aquaculture to deal with bacterial infections, but antibiotic resistance has restricted its application. Therefore, it is necessary to develop drugs on account of novel strategies. Here, aerolysin, the main virulence factor of Aeromonas hydrophila (A. hydrophila), was defined as a target to develop anti-virulence drugs. The results showed that Licochalcone A (LCA) with little bacteriostatic activity could decrease the hemolytic activity of aerolysin without affecting its production. The binding mode and potential binding sites were determined following molecular docking and dynamic simulation. Ser33 and Pro365 were confirmed to be the main binding sites according to the results of fluorescence quenching assay with mutated aerolysin. The mechanism by which LCA inhibited aerolysin was hindering its pore-forming activity. Moreover, cell viability assays and animal studies demonstrated that LCA could provide a significant protection to human alveolar epithelial cells from aerolysin-mediated cell damage and decrease the pathogenicity of A. hydrophila to channel catfish. These findings suggested that LCA might be a novel candidate for treating A. hydrophila infections and partly determined the mechanism of herbal medicine in dealing with bacterial infections.