枸杞槲皮素对金黄色葡萄球菌产β-内酰胺酶的抑制作用OACSTPCD

[Objective]This study was aimed to investigate the inhibitory mechanism of Lycium barbarum quercetin on β-lactamase produced by Staphylococcus aureus,so as to provide a basic basis for the clinical development of β-lactamase inhibitors.[Method]β-lactamase positive strains were screened by penicillin inhibition zone edge test,and the sensitivity of positive strains to penicillin was detected by drug sensitivity paper method under the action of Lycium barbarum quercetin at concentrations of 32,64 and 128 μg/mL.The changes of penicillin content under the treatment of Lycium barbarum quercetin at concentrations of 32,64,128 and 256 μg/mL were detected by multifunctional microplate reader,so as to evaluate the effect of Lycium barbarum quercetin on β-lactamase synthesis and β-lactamase activity under the treatment of Lycium barbarum quercetin at concentrations of 64,128 and 256 μg/mL.The molecular docking of Lycium barbarum quercetin and BlaZ protein was performed by AutoDockTools 1.5.6 software,and the results of molecular docking were visualized by Discovery Studio 2019 Client software.[Result]A total of 23 strains producing β-lactamase positive strains were screened from 36 strains of Staphylococcus aureus.The results of drug sensitivity paper showed that the sensitivity of positive strains to penicillin increased with the increase of Lycium barbarum quercetin concentration.The results of multifunctional microplate reader showed that Lycium barbarum quercetin could inhibit the synthesis of β-lactamase and significantly inhibit the activity of β-lactamase(P＜0.05).Molecular docking results showed that Lycium barbarum quercetin affected the binding of BlaZ protein to β-lactam antibiotics by hydrogen bonding with the conserved residue Asn161 in the Ω-loop region of BlaZ protein.[Conclusion]Lycium barbarum quercetin could reduce the synthesis of β-lactamase,and also enhance the antibacterial effect of penicillin by reducing the activity of β-lactamase,which had potential activity as a β-lactamase inhibitor.The results provided a reference for the subsequent development of new β-lactamase inhibitors.