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工程噬菌体用于靶向根除超级细菌。

Engineering bacteriophages for targeted superbug eradication.

作者信息

Ghaznavi Ghazal, Vosough Parisa, Ghasemian Abdolmajid, Tabar Mohammad Mahdi Mokhtari, Tayebi Lobat, Taghizadeh Saeed, Savardashtaki Amir

机构信息

Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.

Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Mol Biol Rep. 2025 Feb 11;52(1):221. doi: 10.1007/s11033-025-10332-6.

DOI:10.1007/s11033-025-10332-6
PMID:39934535
Abstract

The rise of antibiotic-resistant bacteria, termed "superbugs," presents a formidable challenge to global health. These pathogens, often responsible for persistent nosocomial infections, threaten the effectiveness of conventional antibiotic therapies. This review delves into the potential of bacteriophages, viruses specifically targeting bacteria, as a powerful tool to combat superbugs. We examined the latest developments in genetic engineering that improve the efficacy of bacteriophages, focusing on modifications in host range, lysis mechanisms, and their ability to overcome bacterial defense systems. This review article highlights the CRISPR-Cas system as a promising method for precisely manipulating phage genomes, enabling the development of novel phage therapies with enhanced efficacy and specificity. Furthermore, we discussed developing novel phage-based strategies, such as phage cocktails and phage-antibiotic combinations. We also analyzed the challenges and ethical considerations associated with phage engineering, emphasizing the need for responsible and rigorous research to ensure this technology's safe and effective deployment to combat the growing threat of antibiotic resistance.

摘要

被称为“超级细菌”的抗生素耐药性细菌的出现,对全球健康构成了巨大挑战。这些病原体通常是持续性医院感染的罪魁祸首,威胁着传统抗生素疗法的有效性。本综述深入探讨了噬菌体(专门针对细菌的病毒)作为对抗超级细菌的有力工具的潜力。我们研究了基因工程的最新进展,这些进展提高了噬菌体的功效,重点关注宿主范围、裂解机制的改变以及它们克服细菌防御系统的能力。这篇综述文章强调了CRISPR-Cas系统作为精确操纵噬菌体基因组的一种有前景的方法,能够开发出具有更高功效和特异性的新型噬菌体疗法。此外,我们还讨论了开发基于噬菌体的新策略,如噬菌体鸡尾酒疗法和噬菌体-抗生素联合疗法。我们还分析了与噬菌体工程相关的挑战和伦理考量,强调需要进行负责任且严谨的研究,以确保该技术能够安全有效地用于应对日益严重的抗生素耐药性威胁。

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Engineering bacteriophages for targeted superbug eradication.工程噬菌体用于靶向根除超级细菌。
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引用本文的文献

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Armed Phages: A New Weapon in the Battle Against Antimicrobial Resistance.武装噬菌体:对抗抗生素耐药性的新武器
Viruses. 2025 Jun 27;17(7):911. doi: 10.3390/v17070911.
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Cytokines Meet Phages: A Revolutionary Pathway to Modulating Immunity and Microbial Balance.细胞因子与噬菌体相遇:调节免疫和微生物平衡的革命性途径。
Biomedicines. 2025 May 15;13(5):1202. doi: 10.3390/biomedicines13051202.

本文引用的文献

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Changes to virus taxonomy and the ICTV Statutes ratified by the International Committee on Taxonomy of Viruses (2024).病毒分类学的变化和 ICTV 法规经国际病毒分类学委员会批准(2024 年)。
Arch Virol. 2024 Nov 3;169(11):236. doi: 10.1007/s00705-024-06143-y.
2
Proteomic analysis of carbapenem-resistant Klebsiella pneumoniae outer membrane vesicles under the action of phages combined with tigecycline.碳青霉烯类耐药肺炎克雷伯菌噬菌体联合替加环素作用下的外膜囊泡的蛋白质组学分析。
Ann Clin Microbiol Antimicrob. 2024 Aug 20;23(1):73. doi: 10.1186/s12941-024-00734-y.
3
An effective antibiofilm strategy based on bacteriophages armed with silver nanoparticles.
基于携带银纳米粒子的噬菌体的有效抗生物膜策略。
Sci Rep. 2024 Apr 20;14(1):9088. doi: 10.1038/s41598-024-59866-y.
4
Phage-layer interferometry: a companion diagnostic for phage therapy and a bacterial testing platform.噬菌体层干涉测量法:噬菌体治疗的伴随诊断和细菌检测平台。
Sci Rep. 2024 Mar 12;14(1):6026. doi: 10.1038/s41598-024-55776-1.
5
Potential of phage depolymerase for the treatment of bacterial biofilms.噬菌体脱聚酶在治疗细菌生物膜中的潜力。
Virulence. 2023 Dec;14(1):2273567. doi: 10.1080/21505594.2023.2273567. Epub 2023 Oct 31.
6
Bacteriophages with depolymerase activity in the control of antibiotic resistant Klebsiella pneumoniae biofilms.具有解聚酶活性的噬菌体在控制抗药性肺炎克雷伯氏菌生物膜中的作用。
Sci Rep. 2023 Sep 13;13(1):15188. doi: 10.1038/s41598-023-42505-3.
7
Combating antimicrobial resistance: an evidence-based overview of bacteriophage therapy.抗微生物药物耐药性的对策:噬菌体疗法的循证概述。
Postgrad Med J. 2023 Jun 30;99(1173):654-660. doi: 10.1136/postgradmedj-2022-141546. Epub 2022 Apr 4.
8
Bacteriophages: The promising therapeutic approach for enhancing ciprofloxacin efficacy against bacterial infection.噬菌体:增强环丙沙星治疗细菌感染疗效的有前途的治疗方法。
J Clin Lab Anal. 2023 May;37(9-10):e24932. doi: 10.1002/jcla.24932. Epub 2023 Jun 28.
9
Engineering bacteriophages for enhanced host range and efficacy: insights from bacteriophage-bacteria interactions.工程改造噬菌体以扩大宿主范围并提高疗效:噬菌体与细菌相互作用的见解
Front Microbiol. 2023 May 31;14:1172635. doi: 10.3389/fmicb.2023.1172635. eCollection 2023.
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Antibacterial effects of single phage and phage cocktail against multidrug-resistant Klebsiella pneumoniae isolated from diabetic foot ulcer.噬菌体单剂和鸡尾酒对糖尿病足溃疡分离的多重耐药肺炎克雷伯菌的抗菌作用。
Virus Genes. 2023 Aug;59(4):635-642. doi: 10.1007/s11262-023-02004-z. Epub 2023 May 31.