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

IF 4.8 1区 农林科学 Q1 FOOD SCIENCE & TECHNOLOGY Food Bioscience Pub Date : 2024-09-05 DOI:10.1016/j.fbio.2024.105036
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 ,&nbsp;Zhonghe Wang ,&nbsp;Tong Li ,&nbsp;Qing Li ,&nbsp;Meijin Du ,&nbsp;Wenwen Wang ,&nbsp;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":null,"pages":null},"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 ,&nbsp;Zhonghe Wang ,&nbsp;Tong Li ,&nbsp;Qing Li ,&nbsp;Meijin Du ,&nbsp;Wenwen Wang ,&nbsp;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\":null,\"pages\":null},\"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}
引用次数: 0

摘要

抗生素耐药性和抗生素耐药基因(ARGs)的转移导致了严重的环境威胁,迫切需要有效的监管措施来解决上述问题。因此,本研究构建了金黄色葡萄球菌抗生素耐药性的新型三维定量结构-活性关系。设计出了可降低细菌耐药性 15.19% 的氟喹诺酮(FQ)替代物(CIP-098)和可增强外排泵抑制作用 1.96 倍的抗生素辅助剂(2-苯基喹啉外排泵抑制剂(2P-Q-EPI)替代物(Z-20))。机理分析表明,FQ 中的氢键供体和氢键是必不可少的基团和非共价相互作用,有助于抗生素对抗金黄色葡萄球菌 DNA 回旋酶中从亲水残基过渡到疏水残基的耐药性突变。研究发现,Z-20 很容易与关键氨基酸残基(Phe-16、Ile-19)结合,从而减少 NorA 外排泵蛋白对抗生素的排出,从而抑制细菌对抗生素的耐药性。本研究设计的非抗生素因子调控方案大大降低了(39.70%)金黄色葡萄球菌对 FQ 的外排,并降低了 ARGs 水平转移的风险。该研究提出了一种缓解肠道微生物群中 FQ 抗生素耐药性和 ARGs 转移的新策略,为 FQ 抗生素和 2P-Q-EPI 的绿色开发提供了技术支持。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Food Bioscience
Food Bioscience Biochemistry, 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.
期刊最新文献
Potential applications of antimicrobial peptides from edible insects in the food supply chain: Uses in agriculture, packaging, and human nutrition Electron beam and X-ray irradiation promote extraction of bioactive compounds from walnut green husk: Structural, physicochemical, and functional properties Identification and in silico screening of novel angiotensin-converting enzyme inhibitory peptides from pacific saury: Interaction mechanism, network pharmacology, stability, Caco-2 monolayer transport Pasting, rheology, structural properties and in vitro digestibility of potato starch complexes co-gelatinized with squash polysaccharides Theabrownin, gut microbiota, and obesity: Effects and mechanisms
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1