The Quorum Sensing Inhibitor Qstatin Has Broad-Spectrum Antivirulence Activity Towards Shrimp-Pathogenic Vibrios

The emergence of antibiotic resistance in aquaculture not only makes antibiotic treatments ineffective in aquaculture but also poses a threat to public health. In order to overcome this, novel strategies to control bacterial diseases are needed. Antivirulence therapy, which disrupts virulence without affecting bacterial viability, represents a promising alternative approach. This study evaluated the antivirulence activity of Qstatin against pathogenic vibrios belonging to the Harveyi clade. Qstatin specifically inhibited the three-channel quorum sensing system in Vibrio campbellii, significantly downregulated the expression of quorum sensing-regulated virulence genes (flaA, flaK, vpsR, vpsT, and vhp) and attenuated the corresponding phenotypes: swimming motility was reduced by up to 57% and biofilm formation by up to 76%. Protease activity, in contrast, was slightly increased rather than decreased. Finally, treatment with 100 μM Qstatin significantly increased the survival of gnotobiotic brine shrimp larvae upon challenge with each of 13 tested pathogenic Harveyi clade strains (belonging to the species V. campbellii, V. harveyi, or V. parahaemolyticus), without an impact on Vibrio densities in the rearing water. These findings indicate that Qstatin has a broad-spectrum antivirulence activity against Harveyi clade vibrios by inhibiting quorum sensing, thus supporting its potential as a sustainable disease control agent.