天然产物研究与开发 ›› 2022, Vol. 34 ›› Issue (3): 368-374.doi: 10.16333/j.1001-6880.2022.3.002

• 研究论文 • 上一篇    下一篇

乳酸链球菌素联用美罗培南对耐甲氧西林金黄色葡萄球菌的抑菌作用初探

李   静1，石   璐1，刘   金1，王   君2，答   嵘3，韩   蓓1*   

  1. 1西安交通大学医学部公共卫生学院，西安 710061；2铜川市疾病预防控制中心，铜川 727031；3西安交通大学第一附属医院检验科，西安 710061
  • 出版日期:2022-03-28 发布日期:2022-03-29
  • 基金资助:
    陕西省自然科学基金（2019JM-445）；中央高校基本科研业务费交叉合作项目（xjh012019054）；陕西省卫生健康科研基金（2018E007）

Inhibitory effects of nisin combined with meropenem on methicillin resistant Staphylococcus aureus

LI Jing1,SHI Lu1,LIU Jin1,WANG Jun2,DA Rong3,HAN Bei1*   

  1. 1School of Public Health,Health Science Center of Xi'an Jiaotong University,Xi'an 710061,China;2 Tongchuan City Center for Disease Control and Prevention,Tongchuan 727031,China;3 Department of Clinical Laboratory,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China
  • Online:2022-03-28 Published:2022-03-29

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摘要：

为研究乳酸链球菌素（nisin，NIS）与美罗培南（meropenem，MEM）联用对耐甲氧西林金黄色葡萄球菌（methicillin resistant Staphylococcus aureus，MRSA）的抑菌作用，本研究通过棋盘法联合抑菌试验计算部分抑菌浓度指数（FICI）来评价联用抑菌效果，使用结晶紫染色法半定量检测药物联用对MRSA菌株生物膜生成的影响，最后通过大蜡螟模型观察药物联用对MRSA感染的大蜡螟存活率的影响。结果显示，在乳酸链球菌素组（NIS）、美罗培南组（MEM）和联用组（MEM+NIS）中，MEM+NIS组对三株MRSA分离株均表现为协同抑菌作用，其FICI值分别为0.375、0.5和0.375；作用6 h时，MEM+NIS组与NIS组均可抑制生物膜生成，但组间无统计学差异（P > 0.05）；大蜡螟生存模型显示，五天后，三株MRSA菌株感染的大蜡螟幼虫的MEM+NIS组生存率分别为30%、80%、30%，其中Yn2020051和Yn2020078，MEM+NIS组的大蜡螟幼虫存活率均高于NIS组、MEM组和阳性对照组（PC），差异均有统计学意义（P<0.05）。

关键词: 耐甲氧西林金黄色葡萄球菌, 美罗培南, 乳酸链球菌素, 联用, 协同抑菌

Abstract:

This study explored the antibacterial effect of nisin (NIS) combined with meropenem (MEM) on methicillin resistant Staphylococcus aureus(MRSA).The minimum inhibitory concentration (MIC) was detected by micro broth dilution method,and the fractional inhibitory concentration index (FICI) was calculated by chessboard combined bacteriostasis test to evaluate the inhibitory effect.Crystal violet staining test was used to quantitatively detect the effect of drug combination on the biofilm formation of MRSA isdates.Galleria mellonella model infected by different treated MRSA was established to compare the survival rate.The results showed that the combination of MEM and NIS had synergistic inhibitory effects on the tested three MRSA strains,and the FICI values were 0.375,0.5 and 0.375 respectively.After 6 hours of treatment,both the combination group (MEM+NIS) and the NIS group could inhibit biofilm formation without statistical difference (P > 0.05).The survival rate of G. mellonella showed that after five days,the survival rates of larvae infected by three MRSA strains were 30%,80%,and 30% respectively.For strain Yn2020051 and Yn2020078,the MEM+NIS group had higher survival rate than that of NIS group,MEM group and positive control (PC) group (P<0.05).

Key words: methicillin resistant Staphylococcus aureus, meropenem, nisin, combination, synergistic inhibitory effect

中图分类号:  R378.1

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