Transcriptomic Analysis Reveals the Inhibitory Mechanism of Fisetin Against the Pathogenicity of Aeromonas hydrophila.

Aeromonas hydrophila is an important zoonotic bacterium that is related to multiple diseases in humans, terrestrial animals, and aquatic animals. Bacterial septicemia caused by A. hydrophila often results in high mortality and severe economic losses. Antibiotics, the major approach to dealing with bacterial infections, are limited due to the occurrence of antibiotic resistance. Anti-virulence strategies provide a promising approach to combat resistant bacterial infections. Here, growth curves, hemolysis, biofilm formation, and animal studies were performed to investigate the effect of fisetin against A. hydrophila. Moreover, RNA-seq technology was employed to determine the potent mechanism of fisetin. The results showed that fisetin could dose-dependently reduce the hemolytic activities mediated by aerolysin and hinder biofilm formation. Animal studies showed that treatment with 50 mg/kg fisetin could remarkably reduce the mortality to 40% in the infected group compared with fish in the fisetin-free group. Further, transcriptome analysis demonstrated that there were 565 differentially expressed genes (DEGs) after treatment with 16 μg/mL fisetin. Fisetin significantly impacted the pathways related to oxidative phosphorylation, the citrate cycle, and virulence factor regulation. Furthermore, 159 virulence-related genes were influenced after fisetin treatment. Collectively, these findings revealed that fisetin could mitigate the pathogenicity of A. hydrophila by affecting oxidative phosphorylation and the citrate cycle pathway as well as inhibiting the production of virulence factors. The study not only identified a powerful substance for managing A. hydrophila-associated diseases in aquaculture but also clarified the mechanism of plant medicines in controlling diseases caused by bacterial pathogens.