Apigenin decreases the pathogenicity of Aeromonas hydrophila infection by inhibiting aerolysin activity and interfering with quorum sensing

AIMS: Diseases caused by pathogenic bacteria lead to severe economic losses every year in aquaculture. Aeromonas hydrophila (A. hydrophila) is responsible for a number of diseases in freshwater aquaculture and is regarded as a food-borne pathogen threatening human health. It is difficult to deal with bacterial infections due to the increase in antibiotic resistance in aquaculture. With the understanding of bacterial pathogenesis, developing drugs targeting bacterial virulence has been regarded as a useful approach to alternating antibiotics. METHODS AND RESULTS: In this study, the in vitro anti-virulence efficacies and in vivo therapeutic effect of apigenin were evaluated against A. hydrophila, and results found that apigenin could inhibit the activity of aerolysin (AerA) and production of quorum-sensing (QS)-regulated virulence factors at concentrations much lower than MIC. Molecular dynamics (MD) simulation results showed that apigenin could form a complex with AerA. Then we found that apigenin could block the oligomeric activity of AerA by forming an apigenin-AerA complex, and residues of Pro347 and Pro395 obtained by MD simulation were confirmed to be the main binding sites. The qPCR results demonstrated that apigenin could suppress the transcription of aerA and ahyR genes, which could lead to the decrease of QS-regulated virulence. Furthermore, apigenin could reduce AerA-induced cell injury and mitigate the mortality of channel catfish challenged with A. hydrophila. CONCLUSIONS: The findings partly clarified the mechanism of apigenin in dealing with A. hydrophila infections through anti-virulence strategy, and provided an approach for developing drugs in aquaculture.