土曲霉抗耐药菌活性成分及其逆转耐药性作用研究  

Active Ingredients of Aspergillus Terrestris Against Multi-Drug Resistance and Its Reversal Effect on Bacterial Resistance

作　　者：刘俊 邹慧敏 曾岗[1] 周晓俐 LIU Jun;ZOU Huimin;ZENG Gang;ZHOU Xiaoli(The People′s Hospital of Huarong County,Yueyang,Hunan,China 414200;School of Pharmacy,Guizhou Medical University,Guiyang,Guizhou China 550025)

机构地区：[1]湖南省华容县人民医院,湖南岳阳414200 [2]贵州医科大学药学院,贵州贵阳550025

出　　处：《中国药业》2024年第21期39-43,共5页China Pharmaceuticals

基　　金：国家自然科学基金[81560570]。

摘　　要：目的探讨土曲霉的抗菌活性成分及其对临床耐药菌的逆转作用。方法采用体外抗菌活性导向法及现代分离技术对土曲霉的代谢产物进行活性物质分离,采用核磁共振波谱法和质谱法确定化合物的结构。采用96孔板测定单体化合物对耐药菌的作用,筛选活性成分,并在无抗菌作用的浓度下分析活性成分对抗菌药物、耐药菌株最低抑菌浓度(MIC)的影响,评价活性成分逆转耐药菌耐药性的作用。结果从土曲霉的活性组分中分离出5种化合物,分别为烟曲霉酸(HA,化合物1)、对羟基苯丙酸(化合物2)、对甲氧基苯甲酸(化合物3)、吲哚-3-乙酸(化合物4)、对羟基苯甲酸(化合物5)。HA对多重耐药菌金黄色葡萄球菌、表皮葡萄球菌、屎肠球菌的抑菌圈大小分别为(21.00±0.37)mm、(19.00±0.21)mm、(32.00±0.23)mm。HA在1/2 MICHA的浓度下,使头孢曲松对耐药菌金黄色葡萄球菌、表皮葡萄球菌、屎肠球菌的MIC分别降低了75.00%,75.00%,87.50%,使氨苄西林对上述3种耐药菌的MIC分别降低了75.00%,75.00%,93.75%,使左氧氟沙星和环丙沙星对上述3种耐药菌的MIC均降低了75.00%;HA在1/4 MICHA的浓度下,使头孢曲松、氨苄西林、左氧氟沙星、环丙沙星对耐药菌金黄色葡萄球菌、表皮葡萄球菌的MIC均降低了50.00%,使头孢曲松、氨苄西林、左氧氟沙星、环丙沙星对耐药菌屎肠球菌的MIC分别降低了50.00%,87.50%,50.00%,50.00%;HA在1/8 MICHA的浓度下,使左氧氟沙星、环丙沙星对耐药菌金黄色葡萄球菌的MIC均降低了50.00%,使头孢曲松对耐药菌表皮葡萄球菌的MIC降低了50.00%,使氨苄西林、左氧氟沙星、环丙沙星对耐药菌屎肠球菌的MIC分别降低75.00%,50.00%,50.00%。结论化合物2至化合物5均为从真菌土曲霉代谢物中首次分离出。HA是土曲霉抗多重耐药菌的主要活性成分,对多重耐药菌金黄色葡萄球菌、表皮葡萄球菌和屎肠球菌均有抗菌、逆转耐药Objective To investigate the antibacterial active ingredients of Aspergillus terrestris and its reversal effect on clinical drug-resistant bacteria.Methods The active ingredients from the metabolites of Aspergillus terrestris were isolated by the in vitro antibacterial activity-oriented method and modern separation techniques.The structures of the compounds were determined by nuclear magnetic resonance(NMR)spectroscopy and mass spectrometry.A 96-well plate was used to determine the effect of the monomers on drug-resistant bacteria to screen out the active ingredients,and to analyze the effect of active ingredients on the minimum inhibitory concentration(MIC)of antibiotics and drug-resistant strains at concentrations without antibacterial activity,to evaluate the reversal effect of active ingredients on bacteria resistancedrug-resistant bacteria.Results Five compounds were isolated from the active ingredients of Aspergillus terrestris,namely helvolic acid(HA,compound 1),p-hydroxyphenylpropionic acid(compound 2),p-methoxybenzoic acid(compound 3),1H-Indol-3-ylacetic acid(compound 4),and p-hydroxybenzoic acid(compound 5).The bacteriostatic circles of HA against multidrug-resistant bacteria Staphylococcus aureus,Staphylococcus epidermidis,and Escherichia coli were(21.00±0.37)mm,(19.00±0.21)mm,and(32.00±0.23)mm,respectively.At a concentration of 1/2 MICHA,HA reduced the MIC of ceftriaxone against resistant bacteria Staphylococcus aureus,Staphylococcus epidermidis,and Enterococcus faecium by 75.00%,75.00%,and 87.50%,respectively;HA reduced the MIC of ampicillin against these three resistant bacteria by 75.00%,75.00%,and 93.75%,respectively;HA reduced the MIC of levofloxacin and ciprofloxacin against these three resistant bacteria by 75.00%.At a concentration of 1/4 MICHA,HA reduced the MIC of ceftriaxone,ampicillin,levofloxacin,and ciprofloxacin against drug-resistant bacteria Staphylococcus aureus,Staphylococcus epidermidis by 50.00%;HA reduced the MIC of ceftriaxone,ampicillin,levofloxacin,and ciprofloxacin against

关 键 词：土曲霉 烟曲霉酸 次生代谢产物 抗耐药菌 逆转耐药性 

分 类 号：R978.1[医药卫生—药品]