Targeting Agrobacterium tumefaciens: A Computational Study on Quorum Sensing Inhibition.

Crown gall disease, caused by Agrobacterium tumefaciens, results in significant loss in agricultural productivity losses due to induced tumor-like growths on various crops. The virulence of A. tumefaciens is controlled by its quorum sensing (QS) system, specifically through the TraR protein, which regulates the expression of genes essential for pathogenicity and plasmid transfer. Beyond pathogenic interactions, QS plays a crucial role in the plant microbiome, influencing symbiosis, competition, and plant health. This study aimed to identify QS inhibitors (QSIs) that disrupt TraR-mediated signaling as a novel approach to mitigate crown gall disease while exploring broader implications for plant-microbe interactions. Using a combination of molecular docking, molecular dynamics (MD) simulations, and protein-protein interaction analysis, we screened a library of potential QSIs and identified N-phenylselenourea as a potent candidate with a binding affinity of -8 kcal/mol to TraR. MD simulations confirmed the stability of this compound within the TraR binding pocket, with strong interactions observed with key residues such as Tyr53 and Asp70. Gene Ontology (GO) enrichment analysis supported these findings, highlighting the disruption of critical pathogenic pathways. Our findings underscore the dual benefits of QSIs, offering a targeted strategy to control A. tumefaciens infections while potentially enhancing plant-microbiome interactions for improved plant health. This study lays the groundwork for developing sustainable agricultural practices by leveraging QS disruption to manage plant diseases and promote beneficial microbial communities.