Qikun Pu , Zhonghe Wang , Tong Li , Qing Li , Meijin Du , Wenwen Wang , Yu Li
{"title":"利用新型氟喹诺酮类药物、抗生素佐剂和植物化学物质联合抑制肠道细菌耐药性和耐药基因转移的新型分子内策略","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":"{\"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}","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}
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
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.