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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.

Aeromonas hydrophila is a pathogenic bacterium that can cause serious infections both in humans and aquatic animals. Antibiotics are the main approach for fighting against the pathogen. However, the emergence of antibiotic resistance has resulted in treatment failure. Therefore, drugs with novel strategies need to be developed. Quorum sensing has been recognized as a promising method for identifying anti-virulence drugs against bacterial infections. The aim of this study was to identify novel drugs targeting quorum sensing of A. hydrophila as alternatives of antibiotics in aquaculture. Thus, hemolytic activity, biofilm formation, qPCR and experimental therapeutics assays were conducted. The results showed that sanguinarine inhibited the growth of A. hydrophila at concentrations higher than 16 μg/mL, but the production of aerolysin and biofilm formation was significantly inhibited at sub-inhibitory concentrations by disrupting the quorum sensing system. Cell viability results showed that sanguinarine could provide protection for A549 cells from aerolysin-induced cell injury. In addition, the mortality of channel catfish administered with sanguinarine at a dosage of 20 mg/kg decreased to 40%, which showed a significant decrease compared with fish in positive group. Taken together, these findings demonstrated that anti-virulence strategies can be a powerful weapon for fighting against bacterial pathogens and sanguinarine appears to be a promising candidate in the treatment of A. hydrophila infections. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila is widely distributed in freshwater environments and aquatic products which can cause a variety of infectious diseases to aquatic, terrestrial species and human. However, the emergence of antibiotic resistant strains results in the treatment failure of antibiotics. Therefore, novel strategies need to be clarified. The pathogenesis of the bacterium is composed by the virulence factors, such as hemolytic toxins, biofilm and adhesions. Therefore, aerolysin and biofilm have been developed as targets identifying novel drugs against A. hydrophila infections. In the present study, resveratrol with little anti- A. hydrophila activity could decrease the pathogenesis of A. hydrophila by inhibiting the expression of aerolysin and biofilm formation at sub-inhibitory concentrations. Results of western-blot and qPCR assays demonstrated that RSV could decrease aerolysin and biofilm production by inhibiting aerolysin encoding gene and quorum sensing system. Furthermore, results of cell viability and experimental therapeutics assays indicated that RSV could provide a significant protection both in vitro and in vivo. Taken together, these findings provide a new approach in identifying drugs based on anti-virulence strategies. RSV is a promising candidate anti- A. hydrophila infections by decreasing the production of aerolysin and biofilm. • Resveratrol can decrease the hemolytic activity and biofilm formation by habiting the quorum sensing system. • Resveratrol can provide a significant protection to channel catfish challenged with A. hydrophila. • Findings in the present study offer a novel approach identifying drugs against Aeromonas hydrophila infections. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila is an opportunistic pathogen responsible for a number of diseases in freshwater farming. Moreover, the bacterium has been identified as a zoonotic pathogen that threatens human health. Antibiotics are widely used for treatments of infectious diseases in aquaculture. However, the abuse of antibiotics has led to the emergence of antimicrobial resistant strains. Thus, novel strategies are required against resistant A. hydrophila strains. The quorum sensing (QS) system, involved in virulence factor production and biofilm formation, is a promising target in identifying novel drugs against A. hydrophila infections. In this study, we found that thymol, at sub-inhibitory concentrations, could significantly reduce the production of aerolysin and biofilm formation by inhibiting the transcription of genes aerA, ahyI, and ahyR. These results indicate that thymol inhibits the quorum sensing system. The protective effects of thymol against A. hydrophila mediated cell injury were determined by live/dead assay and lactate dehydrogenase (LDH) release assay. Moreover, the in vivo study showed that thymol could significantly decrease the mortality of channel catfish infected with A. hydrophila. Taken together, these findings demonstrate that thymol could be chosen as a phytotherapeutic candidate for inhibiting quorum sensing system-mediated aerolysin production and biofilm formation in A. hydrophila. [ABSTRACT FROM AUTHOR]