| 甘草酸对多重耐药大肠杆菌的抗菌增敏作用 |
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| 引用本文： | 张鹏,王春光,张子闯,吕建存,王文静,姚姗姗,刘静茹,赵子玉,张铁.甘草酸对多重耐药大肠杆菌的抗菌增敏作用[J].畜牧兽医学报,2021,52(5):1386-1395. |
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| 作者姓名： | 张鹏 王春光 张子闯 吕建存 王文静 姚姗姗 刘静茹 赵子玉 张铁 |
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| 作者单位： | 1. 河北农业大学动物医学院, 保定 071000;2. 江西农业大学动物科技学院, 南昌 330000 |
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| 基金项目： | 国家自然科学基金（31572560）；河北农业大学科学发展基金（JY2020008） |
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| 摘 要： | 多药外排泵转运子AcrB是大肠杆菌产生多重耐药性(MDR)的重要原因和生物学基础.筛选针对大肠杆菌外排泵AcrB的抑制剂有助于解决大肠杆菌多重耐药问题,本试验借助虚拟筛选工具AutoDock Vina以大肠杆菌多药外排泵转运子AcrB为靶点进行筛选,得到结合作用较好的中药单体成分甘草酸,应用DS Visualizer进...
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| 关 键 词： | 虚拟筛选 甘草酸 AcrB |
| 收稿时间： | 2020-09-14 |
Antibacterial and Sensitizing Effects of Glycyrrhizic Acid on Multidrug Resistant Escherichia coli |
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| ZHANG Peng,WANG Chunguang,ZHANG Zichuang,Lü Jiancun,WANG Wenjing,YAO Shanshan,LIU Jingru,ZHAO Ziyu,ZHANG Tie.Antibacterial and Sensitizing Effects of Glycyrrhizic Acid on Multidrug Resistant Escherichia coli[J].Acta Veterinaria et Zootechnica Sinica,2021,52(5):1386-1395. |
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| Authors: | ZHANG Peng WANG Chunguang ZHANG Zichuang Lü Jiancun WANG Wenjing YAO Shanshan LIU Jingru ZHAO Ziyu ZHANG Tie |
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| Institution: | 1. College of Veterinary Medicine, Hebei Agricultural University, Baoding 071000, China;2. College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330000, China |
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| Abstract: | The multidrug efflux transporter AcrB is an important cause and biological basis of multidrug resistance (MDR) in E. coli. To find an AcrB inhibitor to solve the problem of multidrug resistance, AutoDock Vina was used for screening with AcrB as the target in this experiment, and glycyrrhizic acid was obtained. DS Visualizer was employed to analyze interactions, and the combined drug susceptibility test was used to verify the bacteriostasis of glycyrrhizic acid combined with antibiotics. The inhibitory effect of glycyrrhizic acid on AcrB was verified by Nile red efflux assay, test on proton gradient across the inner membrane and test on outer membrane permeability. Finally, the effect of glycyrrhizic acid on AcrB expression-related genes was tested by real-time fluorescence-based quantitative (RFQ)-PCR. The results showed that glycyrrhizic acid formed hydrophobic force with multiple amino acid residues on AcrB protein, and formed multiple hydrogen bonds with the docking site, the binding force is 47.720 4 kJ·mol-1；3.125 mg·mL-1 glycyrrhizic acid, cefotaxime sodium and fosfomycin sodium had synergistic effect on E. coli E320 with fractional inhibitory concentration index (FICI)≤0.5; glycyrrhizic acid could block the efflux of Nile red and has the same tendency as known inhibitor PAβN; 3.125 mg·mL-1 glycyrrhizic acid had no significant effect on outer membrane permeability and proton gradient across the inner membrane; glycyrrhizic acid could significantly increase the expression level of mRNA in negative regulators AcrR and MarR. This experiment proved that glycyrrhizic acid had the potential to become an efflux pump inhibitor to reduce multidrug resistance in E. coli. |
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| Keywords: | virtual screening glycyrrhizic acid AcrB |
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