Targeting Quorum Sensing LsrR Protein in E. coli: A Computational Approach to Screen the Plant Bioactive Compounds as...

Antimicrobial resistance (AMR) in Escherichia coli, driven by biofilm formation and quorum sensing (QS), presents a significant challenge in combating infections, particularly urinary tract infections. This study explored the potential of plant bioactive compounds to inhibit LsrR, a key transcriptional regulator of the QS system, in E. coli. The active site of LsrR was identified using the Sitemap module, which demonstrated high druggability, with a D-score of 0.987. Structure-based virtual screening was used to identify plant-derived inhibitors, followed by docking, binding free energy calculations, and induced-fit docking to evaluate ligand interactions and stability. Chebulinic acid, rutin, and vicine have emerged as potent inhibitors with better docking scores and multiple protein-ligand interactions. Molecular dynamics simulations confirmed the stability of these complexes, highlighting their potential to disrupt QS pathways and inhibit bacterial biofilm formation. These findings suggest that plant bioactive compounds are promising novel therapeutic agents for mitigating AMR in E. coli by targeting LsrR.