In Vitro Antimicrobial Synergistic Activity and the Mechanism of the Combination of Naringenin and Amikacin Against Antibiotic-Resistant Escherichia coli
{"title":"In Vitro Antimicrobial Synergistic Activity and the Mechanism of the Combination of Naringenin and Amikacin Against Antibiotic-Resistant Escherichia coli","authors":"Lankun Yi, Mingze Cao, Xu Chen, Yubin Bai, Weiwei Wang, Xiaojuan Wei, Yuxiang Shi, Yongying Zhang, Tenghe Ma, Zhen Zhu, Jiyu Zhang","doi":"10.3390/microorganisms12091871","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":18667,"journal":{"name":"Microorganisms","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microorganisms","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3390/microorganisms12091871","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Microorganisms (ISSN 2076-2607) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to prokaryotic and eukaryotic microorganisms, viruses and prions. It publishes reviews, research papers and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.