• 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

GntR家族调控因子MSMEG_5174的缺陷通过操纵嘌呤代谢促进对氨基糖苷类抗生素的耐药性。

Deficiency of GntR Family Regulator MSMEG_5174 Promotes Resistance to Aminoglycosides via Manipulating Purine Metabolism.

作者信息

Deng Wanyan, Zheng Zengzhang, Chen Yi, Yang Maoyi, Yan Jun, Li Wu, Zeng Jie, Xie Jianping, Gong Sitang, Zeng Huasong

机构信息

The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou, China.

Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.

出版信息

Front Microbiol. 2022 Jul 11;13:919538. doi: 10.3389/fmicb.2022.919538. eCollection 2022.

DOI:10.3389/fmicb.2022.919538
PMID:35898907
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9309504/
Abstract

The increasing incidence of drug-resistant tuberculosis is still an emergency for global public health and a major obstacle to tuberculosis treatment. Therefore, deciphering the novel mechanisms of antibiotic resistance is crucial for combatting the rapid emergence of drug-resistant strains. In this study, we identified an unexpected role of GntR family transcriptional regulator MSMEG_5174 and its homologous gene Rv1152 in aminoglycoside antibiotic resistance. Deficiency of MSMEG_5174 rendered highly resistant to aminoglycoside antibiotic treatment, and ectopic expression of Rv1152 in MSMEG_5174 mutants restored antibiotic-induced bacterial killing. We further demonstrated that MSMEG_5174 negatively regulates the expression of purine metabolism-related genes and the accumulation of purine metabolites. Moreover, overexpression of xanthine dehydrogenase MSMEG_0871 or xanthine treatment elicited a significant decrease in aminoglycoside antibiotic lethality for . Together, our findings revealed MSMEG_5174 as a metabolic regulator and hint toward unexplored crosstalk between purine metabolism and antibiotic resistance.

摘要

耐药结核病发病率的不断上升仍是全球公共卫生的紧急情况，也是结核病治疗的主要障碍。因此，破解抗生素耐药性的新机制对于对抗耐药菌株的迅速出现至关重要。在本研究中，我们确定了GntR家族转录调节因子MSMEG_5174及其同源基因Rv1152在氨基糖苷类抗生素耐药性中的意外作用。MSMEG_5174的缺失使细菌对氨基糖苷类抗生素治疗具有高度抗性，并且Rv1152在MSMEG_5174突变体中的异位表达恢复了抗生素诱导的细菌杀伤作用。我们进一步证明，MSMEG_5174负向调节嘌呤代谢相关基因的表达和嘌呤代谢产物的积累。此外，黄嘌呤脱氢酶MSMEG_0871的过表达或黄嘌呤处理导致氨基糖苷类抗生素对[具体细菌]的致死率显著降低。总之，我们的研究结果揭示了MSMEG_5174作为一种代谢调节因子，并暗示了嘌呤代谢与抗生素耐药性之间尚未探索的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b1e/9309504/0fc41bc30f6f/fmicb-13-919538-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b1e/9309504/e9bbe0f7ca7f/fmicb-13-919538-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b1e/9309504/2dcce7a45673/fmicb-13-919538-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b1e/9309504/b676dd5b288e/fmicb-13-919538-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b1e/9309504/621fa6759a1e/fmicb-13-919538-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b1e/9309504/0fc41bc30f6f/fmicb-13-919538-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b1e/9309504/e9bbe0f7ca7f/fmicb-13-919538-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b1e/9309504/2dcce7a45673/fmicb-13-919538-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b1e/9309504/b676dd5b288e/fmicb-13-919538-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b1e/9309504/621fa6759a1e/fmicb-13-919538-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b1e/9309504/0fc41bc30f6f/fmicb-13-919538-g005.jpg

相似文献

1
Deficiency of GntR Family Regulator MSMEG_5174 Promotes Resistance to Aminoglycosides via Manipulating Purine Metabolism.GntR家族调控因子MSMEG_5174的缺陷通过操纵嘌呤代谢促进对氨基糖苷类抗生素的耐药性。
Front Microbiol. 2022 Jul 11;13:919538. doi: 10.3389/fmicb.2022.919538. eCollection 2022.
2
Mycobacterium tuberculosis Rv1152 is a Novel GntR Family Transcriptional Regulator Involved in Intrinsic Vancomycin Resistance and is a Potential Vancomycin Adjuvant Target.结核分枝杆菌Rv1152是一种新型的GntR家族转录调节因子，参与固有万古霉素耐药性，是潜在的万古霉素辅助治疗靶点。
Sci Rep. 2016 Jun 28;6:28002. doi: 10.1038/srep28002.
3
Overexpression of a membrane transport system MSMEG_1381 and MSMEG_1382 confers multidrug resistance in Mycobacterium smegmatis.膜转运系统 MSMEG_1381 和 MSMEG_1382 的过度表达赋予耻垢分枝杆菌多药耐药性。
Microb Pathog. 2023 Dec;185:106384. doi: 10.1016/j.micpath.2023.106384. Epub 2023 Oct 12.
4
Integrated Quantitative Proteomics and Metabolome Profiling Reveal MSMEG_6171 Overexpression Perturbing Lipid Metabolism of Leading to Increased Vancomycin Resistance.整合定量蛋白质组学和代谢组学分析揭示MSMEG_6171过表达扰乱脂质代谢导致万古霉素耐药性增加。
Front Microbiol. 2020 Jul 24;11:1572. doi: 10.3389/fmicb.2020.01572. eCollection 2020.
5
Characterization of the Mycobacterial MSMEG-3762/63 Efflux Pump in Drug Efflux.耻垢分枝杆菌MSMEG-3762/63外排泵在药物外排中的特性研究
Front Microbiol. 2020 Dec 3;11:575828. doi: 10.3389/fmicb.2020.575828. eCollection 2020.
6
Insight into the on/off switch that regulates expression of the MSMEG-3762/63 efflux pump in Mycobacterium smegmatis.洞察调控分枝杆菌 MSMEG-3762/63 外排泵表达的开/关开关。
Sci Rep. 2023 Nov 21;13(1):20332. doi: 10.1038/s41598-023-47695-4.
7
A new dehydratase conferring innate resistance to thiacetazone and intra-amoebal survival of Mycobacterium smegmatis.一种赋予耻垢分枝杆菌对氨硫脲先天抗性及胞内生存能力的新型脱水酶。
Mol Microbiol. 2015 Jun;96(5):1085-102. doi: 10.1111/mmi.12992. Epub 2015 Mar 28.
8
Mycobacterium tuberculosis Rv1302 and Mycobacterium smegmatis MSMEG_4947 have WecA function and MSMEG_4947 is required for the growth of M. smegmatis.结核分枝杆菌 Rv1302 和耻垢分枝杆菌 MSMEG_4947 具有 WecA 功能，MSMEG_4947 是耻垢分枝杆菌生长所必需的。
FEMS Microbiol Lett. 2010 Sep 1;310(1):54-61. doi: 10.1111/j.1574-6968.2010.02045.x. Epub 2010 Jun 23.
9
Lsr2 and Its Novel Paralogue Mediate the Adjustment of Mycobacterium smegmatis to Unfavorable Environmental Conditions.Lsr2 及其新的旁系同源物介导分枝杆菌对不利环境条件的适应。
mSphere. 2021 May 12;6(3):e00290-21. doi: 10.1128/mSphere.00290-21.
10
Lack of MSMEG_6281, a peptidoglycan amidase, affects cell wall integrity and virulence of Mycobacterium smegmatis.缺乏肽聚糖酰胺酶 MSMEG_6281 会影响耻垢分枝杆菌的细胞壁完整性和毒力。
Microb Pathog. 2019 Mar;128:405-413. doi: 10.1016/j.micpath.2019.01.013. Epub 2019 Jan 24.

引用本文的文献

1
The impact of bacterial purine metabolism on antibiotic efficacy.细菌嘌呤代谢对抗生素疗效的影响。
NPJ Antimicrob Resist. 2025 Aug 4;3(1):69. doi: 10.1038/s44259-025-00139-7.
2
Inosine reverses multidrug resistance in Gram-negative bacteria carrying mobilized RND-type efflux pump gene cluster .肌苷逆转携带可移动 RND 型外排泵基因簇的革兰氏阴性菌的多重耐药性。
mSystems. 2024 Oct 22;9(10):e0079724. doi: 10.1128/msystems.00797-24. Epub 2024 Sep 10.
3
Dynamic Transcriptional Landscape of under Cold Stress.在冷胁迫下的动态转录组景观。

本文引用的文献

1
The WHO Global Tuberculosis 2021 Report - not so good news and turning the tide back to End TB.世界卫生组织 2021 年全球结核病报告——不容乐观的消息与遏制结核病蔓延的努力
Int J Infect Dis. 2022 Nov;124 Suppl 1:S26-S29. doi: 10.1016/j.ijid.2022.03.011. Epub 2022 Mar 20.
2
Purine Nucleotides Metabolism and Signaling in Huntington's Disease: Search for a Target for Novel Therapies.嘌呤核苷酸代谢与亨廷顿病的信号转导：寻找新疗法的靶点。
Int J Mol Sci. 2021 Jun 18;22(12):6545. doi: 10.3390/ijms22126545.
3
L-lysine potentiates aminoglycosides against via regulation of proton motive force and antibiotics uptake.
Int J Mol Sci. 2023 Aug 11;24(16):12706. doi: 10.3390/ijms241612706.
4
Transcriptional regulation and drug resistance in .在... 中的转录调控和耐药性。
Front Cell Infect Microbiol. 2022 Sep 2;12:990312. doi: 10.3389/fcimb.2022.990312. eCollection 2022.
L-赖氨酸通过调节质子动力势和抗生素摄取增强氨基糖苷类药物对 的作用。
Emerg Microbes Infect. 2020 Mar 20;9(1):639-650. doi: 10.1080/22221751.2020.1740611. eCollection 2020.
4
A White-Box Machine Learning Approach for Revealing Antibiotic Mechanisms of Action.一种揭示抗生素作用机制的白盒机器学习方法。
Cell. 2019 May 30;177(6):1649-1661.e9. doi: 10.1016/j.cell.2019.04.016. Epub 2019 May 9.
5
Incomplete base excision repair contributes to cell death from antibiotics and other stresses.不完全碱基切除修复导致细胞死亡，这种情况既与抗生素等压力有关。
DNA Repair (Amst). 2018 Nov;71:108-117. doi: 10.1016/j.dnarep.2018.08.014. Epub 2018 Aug 25.
6
Disturbed purine nucleotide metabolism in chronic kidney disease is a risk factor for cognitive impairment.慢性肾脏病中嘌呤核苷酸代谢紊乱是认知障碍的一个危险因素。
Med Hypotheses. 2018 Feb;111:36-39. doi: 10.1016/j.mehy.2017.12.016. Epub 2017 Dec 13.
7
Oxidation of dCTP contributes to antibiotic lethality in stationary-phase mycobacteria.dCTP 的氧化会导致静止期分枝杆菌对抗生素的致死作用。
Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):2210-2215. doi: 10.1073/pnas.1719627115. Epub 2018 Jan 30.
8
Modeling the multi-scale mechanisms of macromolecular resource allocation.建立大分子资源分配的多尺度机制模型。
Curr Opin Microbiol. 2018 Oct;45:8-15. doi: 10.1016/j.mib.2018.01.002. Epub 2018 Jan 24.
9
Antibiotic efficacy-context matters.抗生素疗效——具体情况很重要。
Curr Opin Microbiol. 2017 Oct;39:73-80. doi: 10.1016/j.mib.2017.09.002. Epub 2017 Oct 16.
10
Identification of GntR as regulator of the glucose metabolism in Pseudomonas aeruginosa.鉴定 GntR 为铜绿假单胞菌葡萄糖代谢的调控因子。
Environ Microbiol. 2017 Sep;19(9):3721-3733. doi: 10.1111/1462-2920.13871. Epub 2017 Aug 24.