The Role of Phytosterol Derivatives in Inhibiting LuxS-Mediated Quorum Sensing and Biofilm Formation in Vibrio parahaemolyticus.

Vibrio parahaemolyticus, a halophilic bacterium of the Vibrionaceae family, is a notable opportunistic pathogen that affects aquatic organisms, such as shrimp and fish. The LuxS enzyme, a Zn²-dependent metalloenzyme, governs the synthesis of autoinducer-2 (AI-2), a conserved quorum-sensing molecule that modulates gene expression related to virulence in Vibrio species and Escherichia coli. This study aimed to investigate the inhibitory potential of marine algae-derived bioactive compounds against the LuxS/AI-2 quorum-sensing system in Vibrio parahaemolyticus. Structural and functional characterization of the LuxS protein was performed using various bioinformatics tools. Virtual screening and molecular docking of 20 selected compounds identified Brassicasterol as having the strongest binding affinity (- 8.1 kcal/mol), while Stigmasterol, with a slightly lower docking score (- 8.0 kcal/mol), showed greater stability in a 300 ns molecular dynamics (MD) simulation. Subsequent analyses, including Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) and Principal Component Analysis (PCA), confirmed the sustained interaction of Stigmasterol with the LuxS protein. These findings highlight Stigmasterol as a promising inhibitor of LuxS-mediated quorum sensing and support its potential as a candidate for anti-virulence therapeutic intervention in Vibrio parahaemolyticus infections.