Barasarathi Jayanthi, Perveen Kahkashan, Khan Faheema, Muthukumaran M, Debnath Abhijit, Behera Maheswari, Pongen Moaakum, Sayyed Riyaz, Mastinu Andrea
Faculty of Health and Life Sciences (FHLS), INTI International University, Nilai, Negeri Sembilan, Malaysia.
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia.
J Basic Microbiol. 2025 Jul;65(7):e70041. doi: 10.1002/jobm.70041. Epub 2025 Apr 22.
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.
冠瘿病由根癌土壤杆菌引起，由于各种作物上出现类似肿瘤的生长，导致农业生产力大幅损失。根癌土壤杆菌的毒力由其群体感应（QS）系统控制，特别是通过TraR蛋白，该蛋白调节致病性和质粒转移所需基因的表达。除了致病相互作用外，群体感应在植物微生物群中起着关键作用，影响共生、竞争和植物健康。本研究旨在鉴定破坏TraR介导信号传导的群体感应抑制剂（QSIs），作为减轻冠瘿病的新方法，同时探索其对植物-微生物相互作用的更广泛影响。通过分子对接、分子动力学（MD）模拟和蛋白质-蛋白质相互作用分析相结合的方法，我们筛选了一个潜在QSIs文库，并确定N-苯基硒脲是一种有效的候选物，对TraR的结合亲和力为-8 kcal/mol。MD模拟证实了该化合物在TraR结合口袋内的稳定性，观察到与关键残基如Tyr53和Asp70有强烈相互作用。基因本体（GO）富集分析支持了这些发现，突出了关键致病途径的破坏。我们的研究结果强调了QSIs的双重益处，提供了一种靶向策略来控制根癌土壤杆菌感染，同时可能增强植物-微生物相互作用以改善植物健康。本研究通过利用群体感应破坏来管理植物病害和促进有益微生物群落，为发展可持续农业实践奠定了基础。
