Synergistic antimicrobial effect of demethylzeylasteral and meropenem against NDM-1-positive Escherichia coli
10.16303/j.cnki.1005-4545.2024.08.25
- VernacularTitle:去甲泽拉木醛与美罗培南对NDM-1阳性大肠杆菌的协同抗菌作用
- Author:
Zhiying LIU
1
;
Yan GUO
;
Lei XU
;
Hongtao LIU
;
Xuming DENG
;
Jiazhang QIU
Author Information
1. 吉林大学动物医学学院,吉林长春 130062
- Keywords:
demethylzeylasteral;
NDM-1;
meropenem;
synergistic antibacterial activity
- From:
Chinese Journal of Veterinary Science
2024;44(8):1765-1772
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to investigate the synergistic antimicrobial effect of demethylzeylasteral meropenem against NDM-1-positive Escherichia coli.Firstly,the nitrocefin hydrolysis assay and molecular docking assay were used to determine the inhibitory effect and mechanism of demethyl-zeylasteral on the hydrolytic activity of the NDM-1 protein.Secondly,the synergistic bacteriostatic effect of demethylzeylasteral with the carbapenem antibiotic meropenem was confirmed by the checkerboard minimum inhibitory concentration assay,growth curve assay,and inhibition zone as-say.The synergistic bactericidal effect of the combination was further determined by the time-kill-ing assay,live/dead bacterial staining assay,and membrane integrity assay.Finally,the G.mellonel-la infection model demonstrated the protective effect of demethylzeylasteral and meropenem.The results indicated that demethylzeylasteral significantly inhibited the hydrolytic activity of NDM-1(IC50=0.32 mg/L)and competitively affected the binding of NDM-1 to meropenem.In vitro tests showed that demethylzeylasteral had good a synergistic antibacterial effect with meropenem and could exert a synergistic bactericidal effect by enhancing the membrane damage of bacteria caused by meropenem.In vivo assays demonstrated that demethylzeylasteral increased the protective effect of meropenem from 67％to 80％.The results obtained in this study provide a therapeutic strategy and antibacterial synergist for treating NDM-1-positive bacterial infections.
