Virtual screening of quorum sensing inhibitors for Salmonella Typhimurium and their application as preservatives in chicken breast

Quorum sensing inhibitors (QSIs) have been used to inhibit the formation of biofilms produced by foodborne pathogens like Salmonella Typhimurium to improve food safety. However, conventional approaches for screening QSIs are time-consuming and yields random findings. In this study, virtual screening was applied to discover QSIs by targeting LuxS and LsrB, two quorum sensing-related proteins of Salmonella. Twelve QSIs that meet the use in the food industry were identified and their antimicrobial effects were further determined. Esculetin showing the lowest minimum inhibitory concentration (MIC, 500 μ g/mL) was demonstrated to be the most effective antimicrobial against Salmonella Typhimurium. Esculetin displayed significant inhibitory effect on the motility, biofilm formation, extracellular polymer and Autoinducer-2 signaling molecule production of Salmonella Typhimurium. The expression of adrA, lsrb, luxs and rpoS genes related to quorum sensing and biofilm formation was down-regulated by esculetin. This may be because esculetin and LsrB proteins compete to bind, thereby preventing the Autoinducer-2 signaling molecule from entering the membrane and disrupting quorum sensing behavior of Salmonella Typhimurium. After 30 min of treatment, 8 MIC of esculetin could kill 2 log CFU/mL of Salmonella Typhimurium. The study demonstrated that virtual screening employing LuxS and LsrB represented a novel strategy for identifying QSIs for Salmonella. Moreover, the findings indicated that esculetin possessed a quality preservation effect during chicken storage, thereby highlighting its potential as an alternative preservative in the food industry.