Synergistic antibacterial activity of baicalin and EDTA in combination with colistin against colistin-resistant Salmonella

粘菌素 黄芩苷 流出 抗生素 微生物学 化学 药理学 体内 抗菌活性 细菌 生物 生物化学 生物技术 色谱法 遗传学 高效液相色谱法
作者
Xiaodie Cui,Junkai Zhang,Yawei Sun,Fengbin Yan,jin-feng Zhao,Dandan He,Yushan Pan,Li Yuan,Yajun Zhai,Gongzheng Hu
出处
期刊:Poultry Science [Elsevier BV]
卷期号:102 (2): 102346-102346 被引量:22
标识
DOI:10.1016/j.psj.2022.102346
摘要

The emergence and rapid spread of multidrug resistant (MDR) Gram-negative bacteria have posed a serious threat to global health and security. Because of the time-consuming, high cost and high risk of developing new antibiotics, a significant method is to use antibiotic adjuvants to revitalize the existing antibiotics. The purpose of the study is to research the traditional Chinese medicine baicalin with the function of inhibiting the efflux pump and EDTA whether their single or combination can increase the activity of colistin against colistin-resistant Salmonella in vitro and in vivo, and to explore its molecular mechanisms. In vitro antibacterial experiments, we have observed that baicalin and EDTA alone could enhance the antibacterial activity of colistin. At the same time, the combination of baicalin and EDTA also showed a stronger synergistic effect on colistin, reversing the colistin resistance of all Salmonella strains. Molecular docking and RT-PCR results showed that the combination of baicalin and EDTA not only affected the expression of mcr-1, but also was an effective inhibitor of MCR-1. In-depth synergistic mechanism analysis revealed that baicalin and EDTA enhanced colistin activity through multiple pathways, including accelerating the tricarboxylic acid cycle (TCA cycle), inhibiting the bacterial antioxidant system and lipopolysaccharide (LPS) modification, depriving multidrug efflux pump functions and attenuating bacterial virulence. In addition, the combinational therapy of colistin, baicalin and EDTA displayed an obvious reduction in bacterial loads cfus of liver and spleen compared with monotherapy and 2-drug combination therapy. In conclusion, our study indicates that the combination of baicalin and EDTA as a novel colistin adjuvant can provide a reliable basis for formulating the therapeutic regimen for colistin resistant bacterial infection.
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