基于代谢组学及分子对接探究雀石蕊抗MRSA的分子机制  

Molecular mechanism of Cladonia stellaris against MRSA based on metabolomics and molecular docking

作　　者：朱家娜 田红巧 刘梦龙 丁海燕 ZHU Jia-na;TIAN Hong-qiao;LIU Meng-long;DING Hai-yan(School of Public Health,Dali University,Dali 671000,China)

机构地区：[1]大理大学公共卫生学院,大理671000

出　　处：《天然产物研究与开发》2024年第10期1732-1741,共10页Natural Product Research and Development

基　　金：基础研究专项-面上项目(202401AT070076)。

摘　　要：雀石蕊具有良好的体外抗菌活性,为明确其抗菌分子机制,本文以耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)为指示菌,利用代谢组学获取雀石蕊处理MRSA后其胞内差异代谢物变化,并结合分子对接验证差异代谢物相关蛋白酶与雀石蕊抗菌成分的亲和力,分析雀石蕊抗菌机理。体外抗菌实验显示,雀石蕊甲醇提取物抗菌谱广,且对MRSA表现为高度敏感。代谢组学和分子对接结果表明,雀石蕊作用于组氨酸激酶、青霉素结合蛋白PBP2A、喹诺酮类耐药蛋白NorA和S-腺苷甲硫氨酸合成酶4个潜在不同抗菌靶点,增强与MRSA细胞膜黏附且抑制外排泵NorA作用、干扰组氨酸和甲硫氨酸等代谢而发挥抗菌作用。本文结果为后续深入探究雀石蕊抗MRSA分子机制提供依据。The extract of Cladonia stellaris has good in vitro antimicrobial activity.To clarify its antibacterial molecular mechanism,this study used methicillin-resistant Staphylococcus aureus(MRSA)as the indicator bacterium.Metabolomics were used to obtain the changes in intracellular differential metabolites of MRSA treated with C.stellaris,and molecular docking was used to verify the affinity of differential metabolites with relevant proteins and antibacterial components of C.stellaris,analyzing the antibacterial mechanism of C.stellaris.In vitro antibacterial experiments showed that the methanol extract of C.stellaris had a broad antibacterial spectrum and was highly sensitive to MRSA.Metabolomics and molecular docking results indicated that C.stellaris acted on four potential different antibacterial targets:histidine kinase,penicillin-binding protein PBP2A,quinolone resistance protein NorA and S-adenosylmethionine synthetase,enhancing adhesion to MRSA cell membrane and inhibiting the action of efflux pump NorA,interfering with histidine and methionine metabolism to exert antibacterial effects.This study provides a basis for exploring the molecular mechanism of C.stellaris against MRSA.

关 键 词：雀石蕊 MRSA 抗菌机制 代谢组学 分子对接 

分 类 号：TQ465.92[化学工程—制药化工]