甘草酸对多重耐药大肠杆菌的抗菌增敏作用

doi:10.11843/j.issn.0366-6964.2021.05.024

Abstract

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.

Key words: virtual screening, glycyrrhizic acid, AcrB

CLC Number:

S853.74

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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Antibacterial and Sensitizing Effects of Glycyrrhizic Acid on Multidrug Resistant Escherichia coli

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