基于分子对接筛选并探究中药活性单体对大肠埃希菌生物被膜的作用

Screening of active components in Chinese medicine with effects on Escherichia coli biofilm based on molecular docking

摘要:

为了快速准确筛选出抗大肠埃希菌生物被膜的中药活性单体，本研究以大肠埃希菌关键成膜基因csgD为靶点，采用分子对接、分子动力学模拟等方法从中药系统药理学数据库和分析平台(traditional Chinese medicine systems pharmacology database and analysis platform, TCMSP)中筛选抗大肠埃希菌生物被膜的中药活性单体，经体外试验验证抗生物被膜作用后，采用数据独立采集(data-independent acquisition, DIA)蛋白质组学分析筛选到的单体干预大肠埃希菌生物被膜的差异蛋白，并结合表型验证探究其作用机制。通过虚拟筛选获得单宁酸、芸香柚皮苷、丹参酚酸B、迷迭香素4种候选中药活性单体，经验证单宁酸具有明显的抑制大肠埃希菌生物被膜形成的作用。差异蛋白和相关表型验证结果表明，单宁酸主要通过干预大肠埃希菌的菌毛组装、琥珀酸代谢以及群体感应(quorum sensing, QS)系统等影响大肠埃希菌生物被膜形成。本研究为开发防治生物被膜相关感染的新型药物提供了一种候选先导化合物。

Abstract:

By targeting the key gene csgD involved in the biofilm formation of Escherichia coli, we employed molecular docking and molecular dynamics simulation to screen the active components of Chinese medicine with inhibitory effects on the biofilm formation from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). After the anti-biofilm properties of the active components were validated in vitro, data-independent acquisition (DIA) proteomics was employed to further identify the differential proteins involved in interfering with the biofilm formation of Escherichia coli. The mechanisms of inhibition were explored with consideration to the phenotype. Through virtual screening, we identified four candidate active components, including tannic acid, narirutin, salvianolic acid B, and rosmarinic acid. Among them, tannic acid demonstrated significant inhibitory effect on the biofilm formation of E. coli. The analysis of differential proteins, combined with relevant phenotype validation, suggested that tannic acid primarily affected E. coli by intervening in pilus assembly, succinic acid metabolism, and the quorum sensing system. This study provided a lead compound for the development of new drugs against biofilm-associated infections in the future.