Mining and validating quorum sensing interference molecules from food-derived compounds for Salmonella Typhimurium

Abstract

Food-derived compounds represent a promising reservoir for developing novel therapeutic agents against pathogenic infections such as Salmonella Typhimurium. In this study, we integrated computational biology with experimental validation to identify and characterize quorum sensing interference molecules (QSIMs) from food-derived compounds. Through structure-based virtual screening of more than 8000 compounds in the FooDB database, we identified the potential candidates (such as skatole, 2-aminoquinoline, tricarballylic acid, and L-3-phenyllactic acid) demonstrating high affinity binding to the LsrB receptor, as validated by surface plasmon resonance analysis. We further evaluated the performances of the aforementioned QSIMs on strain growth, biofilm formation, and motility. Furthermore, we have also deciphered the corresponding mechanisms and verified the effectiveness of the obtained QSIMs. Finally, we discussed the opportunities and challenges in the development of food-derived QSIMs for weakening virulence, reducing infection and relieving drug resistance of some other pathogens.