Novel insights into the inhibitory effect of pterostilbene targeting Aeromonas hydrophila virulence.

The overuse of antibiotics in aquaculture brings a range of problems. Therefore, novel approaches alternating antibiotics are urgently needed. Strategies targeting bacterial virulence have become one of the routes developing drugs against bacterial infections. Here, we found that pterostilbene (PSE) could inhibit the activity of aerolysin (AerA) and disrupt quorum sensing (QS) at sub-inhibitory concentrations. Molecular docking and dynamics simulation assays were performed to predict the binding mode and binding sites of AerA-PSE complex. Then we confirmed that PSE bound to the sites of Val189 and Ile302 and prevented AerA forming heptamer with transmembrane pores. In addition, PSE could protect to A549 cells and the channel catfish (Ictalurus punctatus) against AerA mediated cell injury and mortality infected with A. hydrophila. The findings demonstrated that targeting bacterial virulence could be a promising measure identifying agents against A. hydrophila infections. • Pterostilbene is an inhibitor of both aerolysin and quorum sensing of Aeromonas hydrophila. • Pterostilbene could reduce the pathogenicity of Aeromonas hydrophila at sub-inhibitory concentrations. • The main binding sites and mechanism of at pterostilbene against aerolysin was confirmed. [ABSTRACT FROM AUTHOR]