• 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

新型 LsrK 配体作为 AI-2 群体感应干扰化合物抑制生物膜形成。

New LsrK Ligands as AI-2 Quorum Sensing Interfering Compounds against Biofilm Formation.

机构信息

Department of Drug Sciences, University of Pavia, Viale Taramelli 12, Pavia 27100, Italy.

Department of Molecular Medicine, Biochemistry Unit, University of Pavia, Viale Taramelli 3/b, Pavia 27100, Italy.

出版信息

J Med Chem. 2024 Oct 24;67(20):18139-18156. doi: 10.1021/acs.jmedchem.4c01266. Epub 2024 Oct 9.

DOI:10.1021/acs.jmedchem.4c01266
PMID:39384180
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11513922/
Abstract

Antimicrobial resistance (AMR) represents a critical global health crisis. An innovative strategy to deal with AMR is to interfere with biofilm formation and bacterial quorum sensing (QS). In this study, newly designed autoinducer-2 (AI-2)-inspired compounds in targeting biofilm-associated infections were evaluated for their ability to inhibit biofilm formation in and . The most effective compounds, , , and , exhibited potent antibiofilm activity with minimal inhibitory concentrations in the low microgram per mL range. Detailed biological assays confirmed that the antibiofilm activity was primarily driven through AI-2 QS inhibition rather than direct antimicrobial effects. The combination of different spectroscopic techniques, such as differential scanning fluorimetry, intrinsic tryptophan fluorescence, circular dichroism, and nuclear magnetic resonance, elucidated the binding between the compounds and the LsrK enzyme, a key player in AI-2 mediated QS. Our findings highlight the potential of these novel QS inhibitors as promising therapeutic agents against biofilm-associated infections.

摘要

抗菌药物耐药性（AMR）是一个全球性的健康危机。一种应对 AMR 的创新策略是干扰生物膜形成和细菌群体感应（QS）。在这项研究中，针对生物膜相关感染，设计了新的自动诱导物-2（AI-2）启发式化合物，评估其抑制 和 中生物膜形成的能力。最有效的化合物 、 、 、 表现出强大的抗生物膜活性，最小抑制浓度在微克/毫升的低水平。详细的生物学检测证实，抗生物膜活性主要是通过 AI-2 QS 抑制而不是直接的抗菌作用。不同光谱技术的组合，如差示扫描荧光法、本征色氨酸荧光法、圆二色性和核磁共振，阐明了化合物与 LsrK 酶（AI-2 介导的 QS 的关键因子）之间的结合。我们的研究结果突出了这些新型 QS 抑制剂作为治疗生物膜相关感染的潜在治疗剂的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/61133332f1ed/jm4c01266_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/adaf83315ab5/jm4c01266_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/d9b3868773f9/jm4c01266_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/4844acc6d809/jm4c01266_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/ef5f8be16cf8/jm4c01266_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/1562973f40ed/jm4c01266_0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/8392192cdb01/jm4c01266_0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/163f22201904/jm4c01266_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/a5619b303fed/jm4c01266_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/ae781a67dfb9/jm4c01266_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/3aed3ce85f7a/jm4c01266_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/1e864f714d4d/jm4c01266_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/61133332f1ed/jm4c01266_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/adaf83315ab5/jm4c01266_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/d9b3868773f9/jm4c01266_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/4844acc6d809/jm4c01266_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/ef5f8be16cf8/jm4c01266_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/1562973f40ed/jm4c01266_0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/8392192cdb01/jm4c01266_0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/163f22201904/jm4c01266_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/a5619b303fed/jm4c01266_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/ae781a67dfb9/jm4c01266_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/3aed3ce85f7a/jm4c01266_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/1e864f714d4d/jm4c01266_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/11513922/61133332f1ed/jm4c01266_0009.jpg

相似文献

1
New LsrK Ligands as AI-2 Quorum Sensing Interfering Compounds against Biofilm Formation.新型 LsrK 配体作为 AI-2 群体感应干扰化合物抑制生物膜形成。
J Med Chem. 2024 Oct 24;67(20):18139-18156. doi: 10.1021/acs.jmedchem.4c01266. Epub 2024 Oct 9.
2
Recent progresses on AI-2 bacterial quorum sensing inhibitors.AI-2 细菌群体感应抑制剂的最新进展。
Curr Med Chem. 2012;19(2):174-86. doi: 10.2174/092986712803414187.
3
Inhibition of Pseudomonas aeruginosa quorum sensing by AI-2 analogs.AI-2类似物对铜绿假单胞菌群体感应的抑制作用。
Bioorg Med Chem Lett. 2009 Jul 15;19(14):3941-4. doi: 10.1016/j.bmcl.2009.03.163. Epub 2009 Apr 9.
4
Altering the communication networks of multispecies microbial systems using a diverse toolbox of AI-2 analogues.利用 AI-2 类似物的多样化工具包改变多物种微生物系统的通讯网络。
ACS Chem Biol. 2012 Jun 15;7(6):1023-30. doi: 10.1021/cb200524y. Epub 2012 Mar 30.
5
Small molecule inhibitors of bacterial quorum sensing and biofilm formation.细菌群体感应和生物膜形成的小分子抑制剂
J Am Chem Soc. 2005 Sep 21;127(37):12762-3. doi: 10.1021/ja0530321.
6
Cadiolide analogues and their precursors as new inhibitors of bacterial quorum sensing and biofilm formation.心脏内酯类似物及其前体作为细菌群体感应和生物膜形成的新型抑制剂。
Bioorg Med Chem Lett. 2022 Feb 1;57:128498. doi: 10.1016/j.bmcl.2021.128498. Epub 2021 Dec 9.
7
Inhibition of quorum sensing-controlled biofilm formation in Pseudomonas aeruginosa by quorum-sensing inhibitors.群体感应抑制剂抑制铜绿假单胞菌生物膜形成。
Microb Pathog. 2017 Oct;111:99-107. doi: 10.1016/j.micpath.2017.08.017. Epub 2017 Aug 14.
8
A New Cell-Based AI-2-Mediated Quorum Sensing Interference Assay in Screening of LsrK-Targeted Inhibitors.基于新型细胞的 AI-2 介导群体感应干扰分析用于 LsrK 靶向抑制剂的筛选。
Chembiochem. 2020 Jul 1;21(13):1918-1922. doi: 10.1002/cbic.201900773. Epub 2020 Mar 3.
9
Design, synthesis and biological evaluation of 4-(alkyloxy)-6-methyl-2H-pyran-2-one derivatives as quorum sensing inhibitors.4-(烷氧基)-6-甲基-2H-吡喃-2-酮衍生物作为群体感应抑制剂的设计、合成及生物学评价
Bioorg Med Chem Lett. 2015 Aug 1;25(15):2913-7. doi: 10.1016/j.bmcl.2015.05.054. Epub 2015 May 28.
10
Tackling Antimicrobial Resistance with Small Molecules Targeting LsrK: Challenges and Opportunities.用靶向 LsrK 的小分子对抗抗微生物药物耐药性：挑战与机遇。
J Med Chem. 2020 Dec 24;63(24):15243-15257. doi: 10.1021/acs.jmedchem.0c01282. Epub 2020 Nov 5.

引用本文的文献

1
A review on small molecular mimics of antimicrobial peptides with an emphasis on the structure-activity relationship perspective.一篇关于抗菌肽小分子模拟物的综述，重点关注构效关系视角。
RSC Med Chem. 2025 Jun 24. doi: 10.1039/d5md00407a.

本文引用的文献

1
Bacterial architects build the biofilm structures.细菌构建者塑造生物膜结构。
Nat Rev Microbiol. 2024 Apr;22(4):187. doi: 10.1038/s41579-024-01020-6.
2
Loratadine Combats Methicillin-Resistant by Modulating Virulence, Antibiotic Resistance, and Biofilm Genes.氯雷他定通过调节毒力、抗生素耐药性和生物膜基因来对抗耐甲氧西林金黄色葡萄球菌。
ACS Infect Dis. 2024 Jan 12;10(1):232-250. doi: 10.1021/acsinfecdis.3c00616. Epub 2023 Dec 28.
3
Biofilms and their role on diseases.生物膜及其在疾病中的作用。
BMC Microbiol. 2023 Jul 31;23(1):203. doi: 10.1186/s12866-023-02954-2.
4
Antimicrobial Resistance: A Growing Serious Threat for Global Public Health.抗菌药物耐药性：对全球公共卫生日益严重的威胁。
Healthcare (Basel). 2023 Jul 5;11(13):1946. doi: 10.3390/healthcare11131946.
5
Baicalein Inhibits the Biofilm and the LuxS/AI-2 System in vitro.黄芩素在体外抑制生物膜和LuxS/AI-2系统。
Infect Drug Resist. 2023 May 9;16:2861-2882. doi: 10.2147/IDR.S406243. eCollection 2023.
6
Structural Insights into the Ligand-LsrK Kinase Binding Mode: A Step Forward in the Discovery of Novel Antimicrobial Agents.结构洞察配体-LsrK 激酶结合模式：发现新型抗菌剂的重要一步。
Molecules. 2023 Mar 10;28(6):2542. doi: 10.3390/molecules28062542.
7
-acetylcysteine (NAC) attenuates quorum sensing regulated phenotypes in PAO1.N-乙酰半胱氨酸（NAC）减弱铜绿假单胞菌PAO1中群体感应调节的表型。
Heliyon. 2023 Feb 28;9(3):e14152. doi: 10.1016/j.heliyon.2023.e14152. eCollection 2023 Mar.
8
Polysaccharides' Structures and Functions in Biofilm Architecture of Antimicrobial-Resistant (AMR) Pathogens.多糖在抗微生物药物耐药（AMR）病原体生物膜结构中的结构和功能。
Int J Mol Sci. 2023 Feb 17;24(4):4030. doi: 10.3390/ijms24044030.
9
Molecular mechanisms of antibiotic resistance revisited.抗生素耐药性的分子机制再探讨。
Nat Rev Microbiol. 2023 May;21(5):280-295. doi: 10.1038/s41579-022-00820-y. Epub 2022 Nov 21.
10
Inhibition of FGFR Signaling by Targeting FGF/FGFR Extracellular Interactions: Towards the Comprehension of the Molecular Mechanism through NMR Approaches.通过靶向 FGF/FGFR 细胞外相互作用抑制 FGFR 信号传导：通过 NMR 方法深入了解分子机制。
Int J Mol Sci. 2022 Sep 17;23(18):10860. doi: 10.3390/ijms231810860.