熊果酸与夫西地酸联用对金黄色葡萄球菌的协同抗菌作用

doi:10.12092/j.issn.1009-2501.2022.06.002

中国临床药理学与治疗学 ›› 2022, Vol. 27 ›› Issue (6): 608-613.doi: 10.12092/j.issn.1009-2501.2022.06.002

熊果酸与夫西地酸联用对金黄色葡萄球菌的协同抗菌作用

张鹏1，汪子姝1，许丽红1，尹向楠1，胡文2，陈春林1

¹宜春学院化学与生物工程学院，宜春 336000，江西；²宜春市人民医院药剂科，宜春 336000，江西

收稿日期:2022-03-29 修回日期:2022-05-13 出版日期:2022-06-26 发布日期:2022-07-08
通讯作者: 陈春林，男，博士，副教授，研究方向：从事临床药学研究。 E-mail: chenchunlinycxy@163.com
作者简介:张鹏，男，在读硕士研究生，研究方向：抗菌药物合理使用。
基金资助:
国家自然科学基金资助项目（81560584）

Synergistic antibacterial effect of ursolic acid combined with fusidic acid on Staphylococcus aureus

ZHANG Peng1, WANG Zishu1, XU Lihong1, YIN Xiangnan1, HU Wen2, CHEN Chunlin1

¹School of Chemical and Biomedical Engineering, Yichun University, Yichun 336000, Jiangxi, China; ²Department of Pharmacy, Yichun Municipal People's Hospital, Yichun 336000, Jiangxi, China

Received:2022-03-29 Revised:2022-05-13 Online:2022-06-26 Published:2022-07-08

摘要/Abstract

摘要： 目的：探讨熊果酸（ursolic acid, UA）与夫西地酸（Fusidic acid, FA）联用对金黄色葡萄球菌（SA）ATCC29213、耐甲氧西林金黄色葡萄球菌（MRSA）ATCC43300的体外抗菌活性及潜在机制。方法：用微量肉汤稀释法、微量棋盘法测定UA与FA联用对SA、MRSA的最小抑菌浓度（MIC），计算部分抑菌浓度指数（FICI），判断联合效应。用时间杀菌曲线法判断UA联合FA的杀菌效果。采用琼脂二倍稀释法测定FA单用及联用UA时的防耐药突变浓度（MPC）和防耐药突变选择窗（MSW）。结晶紫染色法半定量生物膜，连续稀释法测定生物膜内活菌数。结果：UA和FA联用对SA、MRSA FICI分别为0.312 5、0.375。时间杀菌曲线显示，1MIC UA联合1MIC FA组对SA、MRSA有协同杀菌效应。FA对MRSA的MPC为256 μg/mL，联合UA后，MPC下降至8 μg/mL，MPC较单用降低32倍。UA联用FA组生物膜培养48 h和72 h后结晶紫半定量及生物膜内活菌数均较单用FA组明显降低。结论：UA与FA联用对SA、MRSA具有协同作用。

关键词: 熊果酸, 夫西地酸, 金黄色葡萄球菌, 协同

Abstract: AIM: To explore the antibacterial activity and underlying mechanism of ursolic acid combined with fusidic acid against Staphylococcus aureus (SA) ATCC29213 and Methicillin-Resistant Staphylococcus aureus (MRSA) ATCC43300 in vitro. METHODS: The minimum inhibitory concentration (MIC) of the combined use of ursolic acid and fusidic acid on SA, MRSA was determined by the micro broth dilution method and the micro checkerboard method, and the partial inhibitory concentration index (FICI) was calculated to determine the combined effect. And the bactericidal effect of fusidic acid combined with ursolic acid was studied by the time-killing curves. The agar double dilution method was used to determine the anti-drug resistance mutation concentration (MPC) and anti-drug resistance mutation selection window (MSW) of fusidic acid alone and in combination with ursolic acid. The viable count of biofilm carrier were determined by serial dilution method and the semi-quantitative biofilm by crystal violet staining method. RESULTS: The combined use of ursolic acid and fusidic acid for SA and MRSA FICI were 0.312 5 and 0.375, respectively. The time-killing curve showed that 1MIC ursolic acid combined with 1MIC fusidic acid has a synergistic bactericidal effect on SA and MRSA. The MPC of fusidic acid to MRSA was 256 μg/mL and the MSW was 256. After fusidic acid combined with ursolic acid, the MPC decreased to 8 μg/mL. The combined group was significantly reduced compared to the fusidic acid group. The semi-quantitative and biofilm bacterial counts of combined group were markedly decreased compared to the fusidic acid group after the biofilm cultivate for 48 h and 72 h.CONCLUSION: The combined use of UA and FA has a synergistic effect on SA and MRSA.

Key words: ursolic acid, fusidic acid, staphylococcus aureus, synergistic

中图分类号:

R965.2

张鹏, 汪子姝, 许丽红, 尹向楠, 胡文, 陈春林. 熊果酸与夫西地酸联用对金黄色葡萄球菌的协同抗菌作用[J]. 中国临床药理学与治疗学, 2022, 27(6): 608-613.

ZHANG Peng, WANG Zishu, XU Lihong, YIN Xiangnan, HU Wen, CHEN Chunlin. Synergistic antibacterial effect of ursolic acid combined with fusidic acid on Staphylococcus aureus[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(6): 608-613.

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熊果酸与夫西地酸联用对金黄色葡萄球菌的协同抗菌作用

Synergistic antibacterial effect of ursolic acid combined with fusidic acid on Staphylococcus aureus

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