In Vitro Antimicrobial Synergistic Activity and the Mechanism of the Combination of Naringenin and Amikacin Against Antibiotic-Resistant Escherichia coli

文献类型： 外文期刊

第一作者： Yi, Lankun

作者： Yi, Lankun;Cao, Mingze;Chen, Xu;Shi, Yuxiang;Zhang, Yongying;Ma, Tenghe;Zhu, Zhen;Yi, Lankun;Chen, Xu;Bai, Yubin;Wang, Weiwei;Wei, Xiaojuan;Zhang, Jiyu;Yi, Lankun;Chen, Xu;Bai, Yubin;Wang, Weiwei;Wei, Xiaojuan;Zhang, Jiyu;Yi, Lankun;Chen, Xu;Bai, Yubin;Wang, Weiwei;Wei, Xiaojuan;Zhang, Jiyu

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关键词： Escherichia coli; synergistic effect; naringenin; amikacin; antibacterial mechanism

期刊名称：MICROORGANISMS （ 影响因子：4.2； 五年影响因子：4.6 ）

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年卷期： 2024 年 12 卷 9 期

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收录情况： SCI

摘要： Bacterial drug resistance is becoming an increasingly serious problem, and the development of antibacterial synergists is urgently needed. Combining existing antibiotics with promising nonantibiotic agents is one strategy that has been shown to be effective at overcoming the widespread emergence of antibiotic-resistant pathogens. In this study, we investigated the antibacterial activities and mechanism of naringenin (NG) combined with amikacin (AMK) against multidrug-resistant Escherichia coli (E. coli). We first measured the fractional inhibitory concentration (FIC) of NG combined with antibiotics via the checkerboard method. The results indicated that the combination of NG and AMK had a synergistic effect on E. coli ATCC 25922 and E. coli C7F3. In addition, this synergistic effect was verified by time-kill assays. Moreover, scanning electron microscopy (SEM) was used to observe cell morphology. The results showed that the cell wall of E. coli was destroyed. Furthermore, we assessed the leakage of alkaline phosphatase (AKP), K+, and protein. The extracellular AKP activity increased after the combinational group of 1/2MIC NG and 1/2MIC AMK, suggesting an impairment in cell wall permeability. An increase in the leakage of intracellular K+ and protein indicated an increase in cell inner membrane permeability. These results revealed that NG and AMK inhibited E. coli by damaging cell walls and membranes. In addition, PI uptake rapidly increased after treatment with NG and AMK. Confocal laser scanning microscopy (CLSM) revealed that NG caused cell wall and cell membrane damage in E. coli. In summary, our results provide a new strategy for responding to the development of E. coli drug resistance.

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