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伤口感染中的噬菌体和酶疗法:从实验室到临床

Phage and enzyme therapies in wound infections: From lab to bedside.

作者信息

Yang Pan, Li Jing, Song Zhangyong, Chen Bin, Li Shizhu

机构信息

Postdoctoral Research Station, Guangzhou Bay Area Institute of Biomedicine, Guangzhou, Guangdong 510000, China.

School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, China.

出版信息

Chin Med J (Engl). 2025 Sep 5;138(17):2102-2115. doi: 10.1097/CM9.0000000000003626. Epub 2025 Aug 4.

DOI:10.1097/CM9.0000000000003626
PMID:40757407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12407172/
Abstract

Antibiotic-resistant (AR) bacterial wound infections (WIs) impose major burdens on healthcare systems, exacerbated by ineffective therapies and stalled antibiotic development. Phage therapy and phage-derived enzymes have gained traction as potent alternatives, leveraging targeted bactericidal mechanisms to combat AR pathogens. In this review, we summarised the antimicrobial mechanisms of both phage therapy and phage-derived enzymes as antimicrobial therapy, and outlined recent advances in their use for in vitro , in vivo and clinical applications for WI management. In addition, we also highlights recent advancements in their development, driven by genetic engineering, chemical modifications, and artificial intelligence. Finally, we identified the potential barriers and challenges they may encounter in clinical practice and the corresponding strategies to address these issues. The entire review gives us a comprehensive understanding of the latest advances in phages and their derivative enzyme therapies for treating WIs, in the hope that research in this field will continue to improve and innovate, accelerating the transition from the laboratory to application at the bedside and ultimately improving the efficacy of treatment for AR bacterial WIs.

摘要

抗生素耐药(AR)细菌伤口感染(WI)给医疗系统带来了重大负担,无效的治疗方法和停滞不前的抗生素研发使这一负担更加沉重。噬菌体疗法和噬菌体衍生酶作为有效的替代方法受到关注,它们利用靶向杀菌机制对抗AR病原体。在本综述中,我们总结了噬菌体疗法和噬菌体衍生酶作为抗菌疗法的抗菌机制,并概述了它们在体外、体内及临床应用于伤口感染管理方面的最新进展。此外,我们还强调了由基因工程、化学修饰和人工智能推动的它们在开发方面的最新进展。最后,我们确定了它们在临床实践中可能遇到的潜在障碍和挑战以及应对这些问题的相应策略。整个综述使我们全面了解了噬菌体及其衍生酶疗法在治疗伤口感染方面的最新进展,希望该领域的研究将不断改进和创新,加速从实验室到床边应用的转变,并最终提高AR细菌性伤口感染的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4021/12407172/856ac4967263/cm9-138-2102-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4021/12407172/47d1760ab97a/cm9-138-2102-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4021/12407172/856ac4967263/cm9-138-2102-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4021/12407172/47d1760ab97a/cm9-138-2102-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4021/12407172/856ac4967263/cm9-138-2102-g002.jpg

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本文引用的文献

1
Novel delivery systems for phages and lysins in the topical management of wound infections: a narrative review.用于伤口感染局部治疗的噬菌体和溶菌酶新型递送系统:一篇叙述性综述
Front Microbiol. 2025 Jan 27;16:1526096. doi: 10.3389/fmicb.2025.1526096. eCollection 2025.
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Bacteriophage and Phage-Encoded Depolymerase Exhibit Antibacterial Activity Against K9-Type in Mouse Sepsis and Burn Skin Infection Models.噬菌体和噬菌体编码的解聚酶在小鼠脓毒症和烧伤皮肤感染模型中对K9型细菌表现出抗菌活性。
Viruses. 2025 Jan 6;17(1):70. doi: 10.3390/v17010070.
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Targeted Antibacterial Endolysin to Treat Infected Wounds on 3D Full-Thickness Skin Model: XZ.700 Efficacy.
用于治疗3D全层皮肤模型感染伤口的靶向抗菌内溶素:XZ.700的疗效
Pharmaceutics. 2024 Dec 1;16(12):1539. doi: 10.3390/pharmaceutics16121539.
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A blueprint for broadly effective bacteriophage-antibiotic cocktails against bacterial infections.广谱有效噬菌体-抗生素鸡尾酒治疗细菌感染的蓝图。
Nat Commun. 2024 Nov 28;15(1):9987. doi: 10.1038/s41467-024-53994-9.
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Genetically engineered phages and engineered phage-derived enzymes to destroy biofilms of antibiotics resistance bacteria.基因工程噬菌体和工程噬菌体衍生酶用于破坏抗生素抗性细菌的生物膜。
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DeepMineLys: Deep mining of phage lysins from human microbiome.深矿噬菌体裂解酶:从人类微生物组中深度挖掘噬菌体裂解酶。
Cell Rep. 2024 Aug 27;43(8):114583. doi: 10.1016/j.celrep.2024.114583. Epub 2024 Aug 6.
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Discovery of Antimicrobial Lysins from the "Dark Matter" of Uncharacterized Phages Using Artificial Intelligence.利用人工智能从未鉴定噬菌体的“暗物质”中发现抗菌溶菌酶。
Adv Sci (Weinh). 2024 Aug;11(32):e2404049. doi: 10.1002/advs.202404049. Epub 2024 Jun 20.
8
Current Knowledge and Perspectives of Phage Therapy for Combating Refractory Wound Infections.噬菌体疗法在治疗耐药性创面感染中的研究现状和展望。
Int J Mol Sci. 2024 May 17;25(10):5465. doi: 10.3390/ijms25105465.
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J Microbiol Biotechnol. 2024 Jun 28;34(6):1189-1196. doi: 10.4014/jmb.2312.12050. Epub 2024 Feb 28.
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Selective Depletion of Staphylococcus aureus Restores the Skin Microbiome and Accelerates Tissue Repair after Injury.金黄色葡萄球菌选择性耗竭可恢复皮肤微生物组并加速损伤后的组织修复。
J Invest Dermatol. 2024 Aug;144(8):1865-1876.e3. doi: 10.1016/j.jid.2024.01.018. Epub 2024 Feb 1.