A novel in-silico strategy for the combined inhibition of intestinal bacterial resistance and the transfer of resistant genes using new fluoroquinolones, antibiotic adjuvants, and phytochemicals
Qikun Pu , Zhonghe Wang , Tong Li , Qing Li , Meijin Du , Wenwen Wang , Yu Li
{"title":"A novel in-silico strategy for the combined inhibition of intestinal bacterial resistance and the transfer of resistant genes using new fluoroquinolones, antibiotic adjuvants, and phytochemicals","authors":"Qikun Pu , Zhonghe Wang , Tong Li , Qing Li , Meijin Du , Wenwen Wang , Yu Li","doi":"10.1016/j.fbio.2024.105036","DOIUrl":null,"url":null,"abstract":"<div><p>The antibiotic resistance and transfer of antibiotic resistance genes (ARGs) lead to severe environmental threats, and efficient regulatory measures to solve the above problems are urgently needed. Thus, a novel three-dimensional quantitative structure-activity relationship for <em>S. aureus</em> antibiotic resistance was constructed in this study. A fluoroquinolone (FQ) substitute (CIP-098) with decreased bacterial resistance by 15.19% and antibiotic adjuvant (2-phenylquinoline efflux pump inhibitor (2P-Q-EPI) substitute (Z-20)) that enhanced efflux pump inhibition by 1.96 times were designed. Mechanism analysis revealed that hydrogen bond donors and hydrogen bonding in FQ are essential groups and non-covalent interactions, which assist antibiotics in combating resistance mutations in <em>S. aureus's</em> DNA gyrase that transition from hydrophilic to hydrophobic residues. Z-20 was found to easily bind to key amino acid residues (Phe-16, Ile-19), thus reducing the antibiotic expulsion by the NorA efflux pump protein, which can inhibit antibiotic resistance in bacteria. The non-antibiotic factor regulatory scheme designed in this study significantly reduced (by 39.70%) the efflux of FQ by <em>S. aureus</em> and the risk of horizontal ARGs transfer. This study proposes a new strategy to mitigate FQ antibiotic resistance and ARGs transfer in gut microbiota, offering technical support for the green development of FQ antibiotics and 2P-Q-EPI.</p></div>","PeriodicalId":12409,"journal":{"name":"Food Bioscience","volume":"62 ","pages":"Article 105036"},"PeriodicalIF":4.8000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Food Bioscience","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2212429224014664","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"FOOD SCIENCE & TECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The antibiotic resistance and transfer of antibiotic resistance genes (ARGs) lead to severe environmental threats, and efficient regulatory measures to solve the above problems are urgently needed. Thus, a novel three-dimensional quantitative structure-activity relationship for S. aureus antibiotic resistance was constructed in this study. A fluoroquinolone (FQ) substitute (CIP-098) with decreased bacterial resistance by 15.19% and antibiotic adjuvant (2-phenylquinoline efflux pump inhibitor (2P-Q-EPI) substitute (Z-20)) that enhanced efflux pump inhibition by 1.96 times were designed. Mechanism analysis revealed that hydrogen bond donors and hydrogen bonding in FQ are essential groups and non-covalent interactions, which assist antibiotics in combating resistance mutations in S. aureus's DNA gyrase that transition from hydrophilic to hydrophobic residues. Z-20 was found to easily bind to key amino acid residues (Phe-16, Ile-19), thus reducing the antibiotic expulsion by the NorA efflux pump protein, which can inhibit antibiotic resistance in bacteria. The non-antibiotic factor regulatory scheme designed in this study significantly reduced (by 39.70%) the efflux of FQ by S. aureus and the risk of horizontal ARGs transfer. This study proposes a new strategy to mitigate FQ antibiotic resistance and ARGs transfer in gut microbiota, offering technical support for the green development of FQ antibiotics and 2P-Q-EPI.
Food BioscienceBiochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
6.40
自引率
5.80%
发文量
671
审稿时长
27 days
期刊介绍:
Food Bioscience is a peer-reviewed journal that aims to provide a forum for recent developments in the field of bio-related food research. The journal focuses on both fundamental and applied research worldwide, with special attention to ethnic and cultural aspects of food bioresearch.