Aeromonas hydrophila (A. hydrophila) can cause a number of diseases in both human and animals. A. hydrophila-related
infections in aquaculture cause severe economic losses every year throughout the world. The emergence of antibiotic resistance that is due to the abuse of
antibiotics has limited the application of
antibiotics. Thus, novel approaches are needed to combat with treatment failure of
antibiotics caused by resistant bacterial strains.
Aerolysin plays a critical role in the pathogenesis of A. hydrophila and has been considered as a novel target for developing drugs based on anti-virulence strategies. Here, we reported that
luteolin, a natural product with no anti-A. hydrophila activity, could reduce
aerolysin-induced
hemolysis by inhibiting
aerolysin activity. The binding mode was simulated by molecular docking and dynamics simulation. Then the main binding sites were confirmed by fluorescence quenching assays. We found that
luteolin could hindered the formation of functional heptamer of
aerolysin according to the results of the oligomerization assay. Moreover,
luteolin could protect A549 cells from
aerolysin mediated cell death and increase the survival rate of A. hydrophila-infected channel catfish. These findings suggest a novel approach to developing drugs fighting against A. hydrophila, and
luteolin can be a promising drug candidate for treatment of A. hydrophila-associated
infections.