截短侧耳素衍生物ZYY-12h对MRSA菌株的抑菌作用及作用机制研究  

Study on the antibacterial activity and mechanism of a new pleuromutilin derivative ZYY-12h against MRSA

作　　者：孙宇豪 陈恬[1] 林皓楠 邱诗越 范维 修思琴 Sun Yu-hao;Chen Tian;Lin Hao-nan;Qiu Shi-yue;Fan Wei;Xiu Si-qin(Chengdu Medical College,Chengdu 610500)

机构地区：[1]成都医学院基础医学院,成都610500

出　　处：《中国抗生素杂志》2022年第1期22-27,共6页Chinese Journal of Antibiotics

基　　金：国家级“大学生创新创业项目训练计划”项目(No.201913705024);四川省卫生健康委员会普及应用项目(No.19PJ031)。

摘　　要：目的探究截短侧耳素衍生物ZYY-12h对耐甲氧西林金黄色葡萄球菌(MRSA)的抑菌效果及作用机制。方法采用抑菌圈法和微量肉汤稀释法测定MRSA菌株对ZYY-12h的敏感性,在此基础上绘制时间-杀菌曲线;再测量经ZYY-12h处理后的MRSA细菌悬液A_(260)、通过SDS-PAGE电泳观察细菌可溶性蛋白的含量变化和扫描电子显微镜(SEM)观察细菌的形态结构变化来探究其抑菌机制。结果ZYY-12h对MRSA菌株有较强的抑菌活性,其最小抑菌浓度(MIC)为0.125 mg/mL,最小杀菌浓度(MBC)为0.5 mg/mL;经ZYY-12h处理后细菌细胞膜的通透性明显变大,菌体可溶性蛋白含量明显减少,且细菌的外部超微形态结构发生改变。结论截短侧耳素衍生物ZYY-12h对MRSA菌株有明显的抑制作用,且在高浓度下有杀菌作用,其作用机制与改变细菌的膜通透性和抑制细菌蛋白质合成有关。Objective To explore the antibacterial effect and mechanism of ZYY-12h,a new pleuromutilin derivative,on methicillin-resistant Staphylococcus aureus(MRSA).Methods The sensitivity of MRSA to ZYY-12h was measured by the inhibition zone method and the broth dilution method,based on which the time-killing curve was drawn.Then the A_(260) of the bacterial suspension treated with ZYY-12h was measured and the content of soluble proteins of the bacteria was observed by SDS-PAGE electrophoresis and the changes in the morphological structure of the bacteria were observed by Scanning Electron Microscopy to explore its antibacterial mechanism.Results ZYY-12h had strong antibacterial activity against MRSA whose minimum inhibitory concentration(MIC)was 0.125 mg/mL and the minimum bactericidal concentration(MBC)was 0.5 mg/mL;after ZYY-12h’s treatment,the permeability apparently increased,and meanwhile there was a distinct decrease of the soluble protein content of the MRSA.What’s more,the morphological structure of the bacteria changed visibly.Conclusion The pleuromutilin derivative ZYY-12h has a significant inhibitory effect on the MRSA,which has a bactericidal effect at high concentrations.Its mechanism of action is in connection with the change of bacterial membrane permeability and inhibition of bacterial protein synthesis.

关 键 词：截短侧耳素衍生物 耐甲氧西林金黄色葡萄球菌 抗菌活性 抑菌机制 

分 类 号：R978.1[医药卫生—药品]