Identification of TonB-dependent siderophore receptor inhibitors against Flavobacterium columnare using a structure-based high-throughput virtual screening method

文献类型： 外文期刊

第一作者： Li, Minghao

作者： Li, Minghao;Deng, Yongqiang;Li, Minghao;Chen, Baipeng;Xu, Ming;Li, Fulong;Chen, Defang;Huang, Xiaoli;Geng, Yi;Ouyang, Ping

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关键词： Flavobacterium columnare; TonB dependent siderophore receptor; virtual screening; exoxolone; prokaryotic transcriptome

期刊名称：FRONTIERS IN MICROBIOLOGY （ 影响因子：5.2； 五年影响因子：6.2 ）

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年卷期： 2024 年 15 卷

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收录情况： SCI

摘要： TonB-dependent siderophore receptors play a critical transport role for Flavobacterium columnare virulence formation and growth, and have become valuable targets for the development of novel antimicrobial agents. Traditional Chinese medicine has demonstrated notable efficacy in the treatment of fish diseases and includes potential antibacterial agents. Herein, we performed molecular docking-based virtual screening to discover novel TonB-dependent siderophore receptor inhibitors from traditional Chinese medicine and provide information for developing novel antibacterial agents. Firstly, we efficiently obtained 11 potential inhibitors with desirable drug-like characteristics from thousands of compounds in the TCM library based on virtual screening and property prediction. The antibacterial activity of Enoxolone, along with its interaction characteristics, were determined via an MIC assay and molecular dynamic simulation. Transcriptional profiling, along with validation experiments, subsequently revealed that an insufficient uptake of iron ions by bacteria upon binding to the TonB-dependent siderophore receptors is the antibacterial mechanism of Enoxolone. Finally, Enoxolone's acceptable toxicity was illustrated through immersion experiments. In summary, we have used virtual screening techniques for the first time in the development of antimicrobial agents in aquaculture. Through this process, we have identified Enoxolone as a promising compound targeting the TonB-dependent siderophore receptor of F. columnare. In addition, our findings will provide new ideas for the advancement of innovative antimicrobial medications in aquaculture.

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