鼠尾草酸、α-倒捻子素联合不同作用机制抗生素的抗金黄色葡萄球菌作用研究  

Antibacterial effects of carnosic acid or α-mangostin combined with various antibiotics with different mechanisms to Staphylococcus aureus

作　　者：官莹莹 李诗敏 袁干军[1,2] 易厚琴 张同科 Guan Ying-ying;Li Shi-min;Yuan Gan-jun;Yi Hou-qin;Zhang Tong-ke(Biotechnological Engineering Center for Pharmaceutical Research and Development,Jiangxi Agricultural University,Nanchang 330045;College of Bioscience and Engineering,Jiangxi Agricultural University,Nanchang 330045)

机构地区：[1]江西农业大学生物技术药物研发工程中心,南昌330045 [2]江西农业大学生物科学与工程学院,南昌330045

出　　处：《中国抗生素杂志》2023年第4期413-418,共6页Chinese Journal of Antibiotics

基　　金：国家自然科学基金(No.820737458和No.81960636);江西省自然科学基金面上项目(No.20202BABL206156)。

摘　　要：目的探究植物源抗菌天然产物鼠尾草酸、α-倒捻子素分别与抗生素的联合应用效果,发现不同联合应用效果的抗菌组合物。方法分别以敏感金黄色葡萄球菌ATCC25923、耐甲氧西林金黄色葡萄球菌MRSA 01为指示菌株,采用微量肉汤稀释法,测定鼠尾草酸、α-倒捻子素和不同作用机制抗生素对指示菌株的最低抑菌浓度;再采用棋盘格法,分别测定鼠尾草酸、α-倒捻子素与不同作用机制抗生素联用对测试菌株的部分抑菌浓度指数(fractional inhibitory concentration index,FICI)。结果鼠尾草酸、α-倒捻子素联合硫酸庆大霉素对测试菌株的FICI范围分别为0.28~0.62、0.31~0.50,前者对两株测试菌株分别显示协同或无关作用,后者均显示协同作用;鼠尾草酸、α-倒捻子素分别与其他抗生素对测试菌株的FICI范围为0.52~1.12,均显示无关作用。结论靶向细胞膜的鼠尾草酸、α-倒捻子素与作用于核糖体影响细胞膜的氨基糖苷类庆大霉素联用时,主要呈现协同的联合抗菌效果,进一步证实了课题组发现的联合用药效果的相关规律;组合物鼠尾草酸/硫酸庆大霉素对金黄色葡萄球菌的不同菌株既可显示协同,又可显示无关作用,为联合用药防细菌耐药的进一步研究打下了基础。Objective To explore the combinational effects of carnosic acid andα-mangostin,originated from plant antimicrobial natural products,respectively combined with antibiotics,and to discover drug combinations with different combinational effects.Methods The minimum inhibitory concentration(MIC)of carnosic acid,α-mangostin,and antibiotics with various action mechanisms to Staphylococcus aureus ATCC25923 and methicillin-resistant S.aureus(MRSA)MRSA 01,used as indicator strains,were determined using broth microdilution method.Then,the fractional inhibitory concentration indices(FICIs)of carnosic acid orα-mangostin in combination with antibiotics with various action mechanisms were tested using checkerboard method.Results The FICIs of carnosic acid orα-mangostin in combination with gentamycin sulfate against tested strains respectively ranged from 0.28 to 0.62,and from 0.31 to 0.50.The former shows synergistic or independent effects,and the latter shows synergistic effects.Those of carnosic acid orα-mangostin in combination with other antibiotics ranged from 0.516 to 1.125,and all showed indifferent effects.Conclusion Cell membrane-targeted carnosic acid andα-mangostin in combination with gentamycin sulfate,an aminoglycoside antibiotic acting on the ribosome and affecting the cell membrane,mainly showed synergistic effects,and which further confirmed the relevant law of drug combinational effect discovered by our research group.Another,the combinations of carnosic acid and gentamicin sulfate,showing synergistic or indifferent effects on different strains of S.aureus,provide a solid foundation for further research on drug combinations to prevent bacterial resistance.

关 键 词：抗生素 联合用药 鼠尾草酸 α-倒捻子素 金黄色葡萄球菌 

分 类 号：R978[医药卫生—药品]