• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

开启大门：一种用于量化革兰氏阳性菌外排水平的新型诊断分子。

Unlocking the Gates: A Novel Diagnostic Molecule for Quantifying Efflux Levels in Gram-Positive Bacteria.

作者信息

Patil Mrunal, Munteanu Tatiana, Brasseur Gaël, Ferreira Carolina, Costa Sofia Santos, Couto Isabel, Athar Mohd, Asunis Elisa, Vargiu Attilio Vittorio, Viveiros Miguel, DiGiorgio Carole, Brunel Frédéric, Raimundo Jean-Manuel, Camplo Michel, Siri Olivier, Bolla Jean-Michel

机构信息

Aix Marseille Université, CNRS, CINaM UMR 7325, Campus de Luminy, Case 913, Cedex 09, Marseille, 13288, France.

Aix Marseille Université, INSERM, SSA, MCT, Marseille, 13385, France.

出版信息

Adv Healthc Mater. 2025 Apr;14(11):e2404145. doi: 10.1002/adhm.202404145. Epub 2025 Mar 11.

DOI:10.1002/adhm.202404145
PMID:40066601
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12023841/
Abstract

Efflux-mediated antibiotic resistance poses a significant global threat, affecting diverse bacterial species. Clinicians recognize the danger of efflux mechanisms during antibiotic treatment, yet precise diagnostic tools remain unavailable. The antibiogram currently infers abnormal efflux pump activity in clinical isolates, which is subsequently confirmed through transcriptomic or genomic analysis. This study harnesses the colorimetric, fluorescence, and solubility properties of phenazinium derivatives to develop a rapid protocol for detecting bacterial efflux. Among several synthesized phenazinium compounds, the compound demonstrating differential MIC in Staphylococcus efflux mutants and exhibiting appropriate physicochemical properties is selected. A diagnostic protocol is developed using the selected compound to assess efflux levels, categorized as no, weak, or strong, through colorimetry and spectroscopy techniques. Testing on Gram-positive efflux mutants and clinical Staphylococcus isolates further validates the approach. In-silico docking analysis confirms the interaction between the chosen compound and the NorA efflux pump in S. aureus. Flow cytometry is employed to re-evaluate the detection assays. The developed molecule and protocol represent the first known method to evaluate efflux levels in any Gram-positive species through a streamlined and user-friendly process. This pioneering test significantly advances the epidemiological analysis of efflux mechanisms and enables more informed therapeutic decision-making, leading to more effective treatment.

摘要

外排介导的抗生素耐药性构成了重大的全球威胁，影响着多种细菌物种。临床医生认识到抗生素治疗过程中外排机制的危险性，但精确的诊断工具仍然无法获得。目前，抗菌谱可推断临床分离株中异常的外排泵活性，随后通过转录组学或基因组分析加以证实。本研究利用吩嗪鎓衍生物的比色、荧光和溶解性特性，开发了一种检测细菌外排的快速方法。在几种合成的吩嗪鎓化合物中，选择在金黄色葡萄球菌外排突变体中显示出不同最低抑菌浓度（MIC）且具有适当理化性质的化合物。使用所选化合物开发了一种诊断方法，通过比色法和光谱技术评估外排水平，分为无、弱或强。对革兰氏阳性外排突变体和临床金黄色葡萄球菌分离株进行测试进一步验证了该方法。计算机对接分析证实了所选化合物与金黄色葡萄球菌中NorA外排泵之间的相互作用。采用流式细胞术重新评估检测方法。所开发的分子和方法代表了第一种通过简化且用户友好的过程评估任何革兰氏阳性菌外排水平的已知方法。这项开创性测试显著推进了外排机制的流行病学分析，并有助于做出更明智的治疗决策，从而实现更有效的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/d8d10d229669/ADHM-14-0-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/0cc027df067a/ADHM-14-0-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/4f7a9ee604d9/ADHM-14-0-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/ece139726b49/ADHM-14-0-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/8318f88cd7a1/ADHM-14-0-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/c9d8a215eafd/ADHM-14-0-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/96396612811e/ADHM-14-0-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/8fe8ac36fdc3/ADHM-14-0-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/543821314159/ADHM-14-0-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/44693333d637/ADHM-14-0-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/6b9d7816eefb/ADHM-14-0-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/d8d10d229669/ADHM-14-0-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/0cc027df067a/ADHM-14-0-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/4f7a9ee604d9/ADHM-14-0-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/ece139726b49/ADHM-14-0-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/8318f88cd7a1/ADHM-14-0-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/c9d8a215eafd/ADHM-14-0-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/96396612811e/ADHM-14-0-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/8fe8ac36fdc3/ADHM-14-0-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/543821314159/ADHM-14-0-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/44693333d637/ADHM-14-0-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/6b9d7816eefb/ADHM-14-0-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5055/12023841/d8d10d229669/ADHM-14-0-g006.jpg

相似文献

1
Unlocking the Gates: A Novel Diagnostic Molecule for Quantifying Efflux Levels in Gram-Positive Bacteria.开启大门：一种用于量化革兰氏阳性菌外排水平的新型诊断分子。
Adv Healthc Mater. 2025 Apr;14(11):e2404145. doi: 10.1002/adhm.202404145. Epub 2025 Mar 11.
2
Unlocking bacterial defense: Exploring the potent inhibition of NorA efflux pump by coumarin derivatives in Staphylococcus aureus.解锁细菌防御：探索香豆素衍生物对金黄色葡萄球菌 NorA 外排泵的强效抑制作用。
Microb Pathog. 2024 May;190:106608. doi: 10.1016/j.micpath.2024.106608. Epub 2024 Mar 20.
3
In vitro and in silico inhibitory effects of synthetic and natural eugenol derivatives against the NorA efflux pump in Staphylococcus aureus.体外和计算机模拟研究合成和天然丁香酚衍生物对金黄色葡萄球菌 NorA 外排泵的抑制作用。
Food Chem. 2021 Feb 1;337:127776. doi: 10.1016/j.foodchem.2020.127776. Epub 2020 Aug 5.
4
In vitro and in silico effect of meldrum's acid-derived compounds on Staphylococcus aureus strains as NorA efflux pump inhibitors.米氏酸衍生化合物对金黄色葡萄球菌菌株作为 NorA 外排泵抑制剂的体外和计算机模拟研究。
Biophys Chem. 2025 Jan;316:107344. doi: 10.1016/j.bpc.2024.107344. Epub 2024 Oct 18.
5
1,3,4-oxadiazole conjugates of capsaicin as potent NorA efflux pump inhibitors of Staphylococcus aureus.1,3,4-噁二唑类辣椒素缀合物作为金黄色葡萄球菌 NorA 外排泵的有效抑制剂。
Bioorg Chem. 2021 Aug;113:105031. doi: 10.1016/j.bioorg.2021.105031. Epub 2021 May 27.
6
Potentiating the intracellular killing of Staphylococcus aureus by dihydroquinazoline analogues as NorA efflux pump inhibitor.二氢喹唑啉类似物作为 NorA 外排泵抑制剂增强金黄色葡萄球菌的细胞内杀伤作用。
Bioorg Med Chem. 2022 Jan 15;54:116580. doi: 10.1016/j.bmc.2021.116580. Epub 2021 Dec 17.
7
Aminoguanidine hydrazones (AGH's) as modulators of norfloxacin resistance in Staphylococcus aureus that overexpress NorA efflux pump.氨基胍腙（AGH's）作为金黄色葡萄球菌中诺氟沙星耐药性的调节剂，该金黄色葡萄球菌过表达NorA外排泵。
Chem Biol Interact. 2018 Jan 25;280:8-14. doi: 10.1016/j.cbi.2017.12.009. Epub 2017 Dec 5.
8
Discovery of novel dihydronaphthalene-imidazole ligands as potential inhibitors of Staphylococcus aureus multidrug resistant NorA efflux pump: A combination of experimental and in silico molecular docking studies.发现新型二氢萘并咪唑类化合物作为耐多药金黄色葡萄球菌 NorA 外排泵的潜在抑制剂：实验与计算分子对接研究的结合。
Microb Pathog. 2024 May;190:106627. doi: 10.1016/j.micpath.2024.106627. Epub 2024 Mar 21.
9
Synthesis, biological evaluation and computational studies of acrylohydrazide derivatives as potential Staphylococcus aureus NorA efflux pump inhibitors.丙烯酰肼衍生物的合成、生物评价及计算研究作为潜在的金黄色葡萄球菌 NorA 外排泵抑制剂。
Bioorg Chem. 2020 Nov;104:104225. doi: 10.1016/j.bioorg.2020.104225. Epub 2020 Aug 26.
10
Thiazolidinedione and thiazole derivatives potentiate norfloxacin activity against NorA efflux pump over expression in Staphylococcus aureus 1199B strains.噻唑烷二酮和噻唑衍生物增强了诺氟沙星对金黄色葡萄球菌 1199B 株中 NorA 外排泵过表达的活性。
Bioorg Med Chem. 2019 Sep 1;27(17):3797-3804. doi: 10.1016/j.bmc.2019.07.006. Epub 2019 Jul 4.

本文引用的文献

1
Current and Future Technologies for the Detection of Antibiotic-Resistant Bacteria.检测抗生素耐药细菌的当前及未来技术
Diagnostics (Basel). 2023 Oct 18;13(20):3246. doi: 10.3390/diagnostics13203246.
2
Resveratrol as an Inhibitor of the NorA Efflux Pump and Resistance Modulator in .白藜芦醇作为诺氟沙星外排泵抑制剂及耐药调节剂在……中
Antibiotics (Basel). 2023 Jul 10;12(7):1168. doi: 10.3390/antibiotics12071168.
3
Role of bacterial efflux pumps in antibiotic resistance, virulence, and strategies to discover novel efflux pump inhibitors.
细菌外排泵在抗生素耐药性、毒力和发现新型外排泵抑制剂策略中的作用。
Microbiology (Reading). 2023 May;169(5). doi: 10.1099/mic.0.001333.
4
Synthesis and antimicrobial testing of 5-fluorouracil derivatives.5-氟尿嘧啶衍生物的合成与抗菌活性测试。
Arch Pharm (Weinheim). 2023 Jul;356(7):e2300103. doi: 10.1002/ardp.202300103. Epub 2023 May 18.
5
Exploring Efflux as a Mechanism of Reduced Susceptibility towards Biocides and Fluoroquinolones in .探索外排作为[具体对象]对杀菌剂和氟喹诺酮类药物敏感性降低的一种机制。 （注：原文中“in.”后面缺少具体内容）
Animals (Basel). 2023 Apr 6;13(7):1270. doi: 10.3390/ani13071270.
6
Molecular design strategy of fluorogenic probes based on quantum chemical prediction of intramolecular spirocyclization.基于分子内螺环化量子化学预测的荧光探针分子设计策略
Commun Chem. 2020 Jun 26;3(1):82. doi: 10.1038/s42004-020-0326-x.
7
Role of PatAB Transporter in Efflux of Levofloxacin in .PatAB转运蛋白在左氧氟沙星外排中的作用 于……
Antibiotics (Basel). 2022 Dec 17;11(12):1837. doi: 10.3390/antibiotics11121837.
8
Early appropriate diagnostics and treatment of MDR Gram-negative infections.多重耐药革兰氏阴性菌感染的早期适当诊断与治疗。
JAC Antimicrob Resist. 2022 Sep 13;4(5):dlac089. doi: 10.1093/jacamr/dlac089. eCollection 2022 Oct.
9
Taking stock of global commitments on antimicrobial resistance.评估全球对抗微生物药物耐药性的承诺。
BMJ Glob Health. 2022 May;7(5). doi: 10.1136/bmjgh-2021-008159.
10
AB-DB: Force-Field parameters, MD trajectories, QM-based data, and Descriptors of Antimicrobials.AB-DB：力场参数、MD 轨迹、基于 QM 的数据和抗菌剂描述符。
Sci Data. 2022 Apr 1;9(1):148. doi: 10.1038/s41597-022-01261-1.