Xanthoxylin as a quorum-sensing inhibitor of Aeromonas hydrophila with promising therapeutic effects.

Aeromonas hydrophila (A. hydrophila) is widely spread in different aquatic environments and still poses a serious threat to the health of aquatic animals. Nevertheless, with the emergence of drug-resistant A. hydrophila, antibiotics have shown limited efficacy as primary therapeutic agents, and novel treatment strategies are urgently needed. The increasing understanding of anti-virulence and anti-quorum-sensing (QS) strategies offers new hope for drug discovery against A. hydrophila infections, which aim not to inhibit or kill bacteria but to reduce pathogenicity by reducing the production or activity of virulence factors. Here, xanthoxylin was screened out, and some tests were conducted on virulence phenotypes and therapeutic effects; the results demonstrated that xanthoxylin lacked anti-A. hydrophila effect could reduce the levels of QS-mediated virulence factors and the transcription of the aerA, ahyR, and ahyI genes. Further therapeutic results showed that xanthoxylin could protect A549 cells from cytotoxicity induced by aerolysin and improve the survival rate of crucian carp (Carassius auratus gibelio) challenged with A. hydrophila. Therefore, xanthoxylin could be a potential QS inhibitor for controlling A. hydrophila infections in aquaculture.