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细菌嘌呤代谢对抗生素疗效的影响。

The impact of bacterial purine metabolism on antibiotic efficacy.

作者信息

Stevens Claire E, Deventer Ashley T, Hobbs Joanne K

机构信息

Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK.

出版信息

NPJ Antimicrob Resist. 2025 Aug 4;3(1):69. doi: 10.1038/s44259-025-00139-7.

DOI:10.1038/s44259-025-00139-7
PMID:40760091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12322280/
Abstract

Metabolism plays a key role in the three antibiotic evasion strategies used by bacteria: tolerance, persistence and resistance. Modulation of purine metabolism is emerging as a common, and clinically relevant, contributor to tolerant and resistant phenotypes. However, whether high or low purine levels promote reduced antibiotic efficacy is unclear. Here, we review and explore the evidence for a relationship between cellular purine levels and antibiotic efficacy.

摘要

代谢在细菌采用的三种抗生素逃避策略(耐受、持留和抗性)中起着关键作用。嘌呤代谢的调节正成为导致耐受和抗性表型的一个常见且与临床相关的因素。然而,嘌呤水平的高低是否会导致抗生素疗效降低尚不清楚。在此,我们回顾并探究细胞嘌呤水平与抗生素疗效之间关系的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e40/12322280/ea5f270ef92d/44259_2025_139_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e40/12322280/9b9d4a857c8e/44259_2025_139_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e40/12322280/ea5f270ef92d/44259_2025_139_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e40/12322280/9b9d4a857c8e/44259_2025_139_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e40/12322280/ea5f270ef92d/44259_2025_139_Fig2_HTML.jpg

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1
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本文引用的文献

1
Staphylococcus aureus COL: An Atypical Model Strain of MRSA That Exhibits Slow Growth and Antibiotic Tolerance due to a Mutation in PRPP Synthetase.金黄色葡萄球菌COL:一种耐甲氧西林金黄色葡萄球菌的非典型模式菌株,由于PRPP合成酶突变而表现出生长缓慢和抗生素耐受性。
Mol Microbiol. 2025 Sep;124(3):189-203. doi: 10.1111/mmi.70000. Epub 2025 Jun 9.
2
Metabolic state-driven nutrient-based approach to combat bacterial antibiotic resistance.基于代谢状态的营养方法对抗细菌抗生素耐药性
NPJ Antimicrob Resist. 2025 Apr 4;3(1):24. doi: 10.1038/s44259-025-00092-5.
3
Metabolic mutations reduce antibiotic susceptibility of E. coli by pathway-specific bottlenecks.
代谢突变通过特定途径瓶颈降低大肠杆菌对抗生素的敏感性。
Mol Syst Biol. 2025 Mar;21(3):274-293. doi: 10.1038/s44320-024-00084-z. Epub 2025 Jan 2.
4
Resensitizing β-Lactams by Reprogramming Purine Metabolism in Small Colony Variant for Osteomyelitis Treatment.通过重编程小菌落变异体中的嘌呤代谢使β-内酰胺类药物重新敏感化用于骨髓炎治疗
Adv Sci (Weinh). 2025 Feb;12(5):e2410781. doi: 10.1002/advs.202410781. Epub 2024 Dec 10.
5
Antibiotic tolerance among clinical isolates: mechanisms, detection, prevalence, and significance.临床分离株中的抗生素耐受性:机制、检测、流行情况及意义。
Clin Microbiol Rev. 2024 Dec 10;37(4):e0010624. doi: 10.1128/cmr.00106-24. Epub 2024 Oct 4.
6
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.
7
A journey into the regulatory secrets of the purine nucleotide biosynthesis.嘌呤核苷酸生物合成调控奥秘之旅。
Front Pharmacol. 2024 Feb 20;15:1329011. doi: 10.3389/fphar.2024.1329011. eCollection 2024.
8
Dynamical model of antibiotic responses linking expression of resistance genes to metabolism explains emergence of heterogeneity during drug exposures.抗生素反应的动力学模型将耐药基因的表达与代谢联系起来,解释了药物暴露过程中异质性的出现。
Phys Biol. 2024 Apr 2;21(3):036002. doi: 10.1088/1478-3975/ad2d64.
9
The Purine Biosynthesis Repressor, PurR, Contributes to Vancomycin Susceptibility of Methicillin-resistant Staphylococcus aureus in Experimental Endocarditis.嘌呤生物合成抑制剂 PurR 有助于耐甲氧西林金黄色葡萄球菌实验性心内膜炎对万古霉素的敏感性。
J Infect Dis. 2024 Jun 14;229(6):1648-1657. doi: 10.1093/infdis/jiad577.
10
Tradeoffs in bacterial physiology determine the efficiency of antibiotic killing.细菌生理学中的权衡决定了抗生素杀菌的效率。
Proc Natl Acad Sci U S A. 2023 Dec 19;120(51):e2312651120. doi: 10.1073/pnas.2312651120. Epub 2023 Dec 14.