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噬菌体疗法:对抗细菌对噬菌体耐药性的演变

Phage Therapy: Combating Evolution of Bacterial Resistance to Phages.

作者信息

Abedon Stephen T

机构信息

Department of Microbiology, The Ohio State University, Mansfield, OH 44906, USA.

出版信息

Viruses. 2025 Aug 8;17(8):1094. doi: 10.3390/v17081094.

DOI:10.3390/v17081094
PMID:40872808
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12390681/
Abstract

Treatments for bacterial infections can be less effective due to toxicities, bacterial tolerance, or genetic resistance to antibacterial agents. The emphasis here is on combating genetic bacterial resistance to bacteriophages. Commonly described simply as phages, bacteriophages are the viruses of bacteria. As phage therapies, they are one of the oldest clinical treatments for bacterial infections. Thwarting bacterial evolution of resistance to phages, particularly during phage treatments, typically involves targeting more than one bacterial characteristic. This can be achieved serially, involving phage substitution after bacterial resistance has become problematic, something that is used especially during more personalized therapies. Substitution phages can be sourced in various ways. This includes as autophages, from phage banks, or via phage training-all as considered here-as well as through phage engineering. An alternative approach is preventing bacterial mutations from occurring at all. In addition, there is simultaneous targeting of multiple bacterial characteristics. These latter strategies include all of the following: using phages that target bacterial fitness or virulence determinants, employing individual phages that recognize multiple receptors, using phage cocktails, or applying phages in combination with antibiotics. This review discusses these different approaches for combating treatment resistance, highlighting various pros and cons.

摘要

由于毒性、细菌耐受性或对抗菌剂的遗传抗性,细菌感染的治疗可能效果较差。这里的重点是对抗细菌对噬菌体的遗传抗性。噬菌体通常简称为噬菌体,是细菌的病毒。作为噬菌体疗法,它们是治疗细菌感染最古老的临床方法之一。阻止细菌对噬菌体产生抗性的进化,特别是在噬菌体治疗期间,通常需要针对不止一种细菌特征。这可以通过连续的方式实现,即在细菌抗性出现问题后进行噬菌体替换,这在更个性化的治疗中尤为常用。替换噬菌体可以通过多种方式获得。这包括作为自噬噬菌体、从噬菌体库中获取、通过噬菌体训练(这里都有考虑)以及通过噬菌体工程。另一种方法是完全防止细菌发生突变。此外,还有同时针对多种细菌特征的方法。这些后一种策略包括以下所有方法:使用靶向细菌适应性或毒力决定因素的噬菌体、使用识别多种受体的单个噬菌体、使用噬菌体鸡尾酒或联合使用噬菌体与抗生素。本综述讨论了这些对抗治疗抗性的不同方法,突出了各种优缺点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfbb/12390681/77205d6a912a/viruses-17-01094-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfbb/12390681/ce5d50ebc8f5/viruses-17-01094-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfbb/12390681/636ded11df47/viruses-17-01094-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfbb/12390681/3d6b0fb54a97/viruses-17-01094-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfbb/12390681/77205d6a912a/viruses-17-01094-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfbb/12390681/ce5d50ebc8f5/viruses-17-01094-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfbb/12390681/636ded11df47/viruses-17-01094-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfbb/12390681/3d6b0fb54a97/viruses-17-01094-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfbb/12390681/77205d6a912a/viruses-17-01094-g004.jpg

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本文引用的文献

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Phage steering in the presence of a competing bacterial pathogen.在存在竞争性细菌病原体的情况下进行噬菌体导向。
Microbiol Spectr. 2025 Jul;13(7):e0288224. doi: 10.1128/spectrum.02882-24. Epub 2025 Jun 10.
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Implementation challenges of personalised phage therapy.个性化噬菌体疗法的实施挑战。
Lancet. 2025 May 31;405(10493):1901-1903. doi: 10.1016/S0140-6736(25)00737-8.
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Re-evaluating what makes a phage unsuitable for therapy.重新评估导致噬菌体不适合用于治疗的因素。
NPJ Antimicrob Resist. 2025 May 29;3(1):45. doi: 10.1038/s44259-025-00117-z.
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Leveraging collateral sensitivity to counteract the evolution of bacteriophage resistance in bacteria.利用旁系敏感性来对抗细菌中噬菌体抗性的演变。
mLife. 2025 Mar 18;4(2):143-154. doi: 10.1002/mlf2.70003. eCollection 2025 Apr.
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Bypassing Evolution of Bacterial Resistance to Phages: The Example of Hyper-Aggressive Phage 0524phi7-1.绕过细菌对噬菌体的抗性进化:超攻击性噬菌体0524phi7-1的实例
Int J Mol Sci. 2025 Mar 23;26(7):2914. doi: 10.3390/ijms26072914.
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Insertion sequence-mediated phage resistance contributes to attenuated colonization of cytolytic variants in the gut.插入序列介导的噬菌体抗性有助于细胞溶解变体在肠道中的定殖减弱。
Microbiol Spectr. 2025 Apr 15;13(5):e0330324. doi: 10.1128/spectrum.03303-24.
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Harnessing Bacteriophages for Sustainable Crop Protection in the Face of Climate Change.在气候变化背景下利用噬菌体实现可持续作物保护
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