文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
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
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
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 @ 2025

在存在竞争性细菌病原体的情况下进行噬菌体导向。

Phage steering in the presence of a competing bacterial pathogen.

作者信息

Czerwinski Sean, Gurney James

机构信息

School of Biology, Georgia State University, Atlanta, Georgia, USA.

出版信息

Microbiol Spectr. 2025 Jul;13(7):e0288224. doi: 10.1128/spectrum.02882-24. Epub 2025 Jun 10.


DOI:10.1128/spectrum.02882-24
PMID:40492711
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12211013/
Abstract

The rise of antibiotic-resistant bacteria has necessitated the development of alternative therapeutic strategies, such as bacteriophage therapy, where viruses infect bacteria, reducing bacterial burden. However, rapid bacterial resistance to phage treatment remains a critical challenge, potentially leading to failure. Phage steering, which leverages the evolutionary dynamics between phage and bacteria, offers a novel solution by driving bacteria to evolve away from virulence factors or resistance mechanisms. In this study, we examined whether phage steering using bacteriophage Luz19 could function in the presence of a competing pathogen, () (USA300), while targeting (PAO1). Through co-evolution experiments with and without the competitor, we observed that Luz19 consistently steered away from the Type IV pilus (T4P), a key virulence factor, without interference from . Genomic analyses revealed mutations in T4P-associated genes, including and , which conferred phage resistance. Our findings suggest that phage steering remains effective even in polymicrobial environments, providing a promising avenue for enhancing bacteriophage therapy efficacy in complex infections.IMPORTANCEPhage steering-using phages that bind essential virulence or resistance-associated structures-offers a promising solution by selecting for resistance mutations that attenuate pathogenic traits. However, it remains unclear whether this strategy remains effective in polymicrobial contexts, where interspecies interactions may alter selective pressures. Here, we demonstrate that evolves phage resistance via loss-of-function mutations in Type IV pilus (T4P) when challenged with the T4P-binding phage Luz19 and that this evolutionary trajectory is preserved even in the presence of a competing pathogen, . Phage resistance was phenotypically confirmed via twitching motility assays and genotypically via whole-genome sequencing. These findings support the robustness of phage steering under interspecies competition, underscoring its translational potential for managing complex infections-such as those seen in cystic fibrosis-where microbial diversity is the norm.

摘要

抗生素耐药细菌的出现使得开发替代治疗策略成为必要,例如噬菌体疗法,即病毒感染细菌,减轻细菌负荷。然而,细菌对噬菌体治疗的快速耐药性仍然是一个关键挑战,可能导致治疗失败。噬菌体导向利用噬菌体与细菌之间的进化动态,通过促使细菌远离毒力因子或耐药机制提供了一种新的解决方案。在本研究中,我们研究了使用噬菌体Luz19进行的噬菌体导向在存在竞争性病原体(USA300)的情况下,同时靶向铜绿假单胞菌(PAO1)时是否能发挥作用。通过有或没有竞争者的共同进化实验,我们观察到Luz19始终引导铜绿假单胞菌远离IV型菌毛(T4P),这是一种关键的毒力因子,且不受USA300的干扰。基因组分析揭示了T4P相关基因中的突变,包括pilA和pilC,这些突变赋予了噬菌体抗性。我们的研究结果表明,即使在多微生物环境中,噬菌体导向仍然有效,为提高噬菌体疗法在复杂感染中的疗效提供了一条有前景的途径。重要性噬菌体导向——使用结合必需毒力或抗性相关结构的噬菌体——通过选择减弱致病性状的抗性突变提供了一种有前景的解决方案。然而,尚不清楚这种策略在多微生物环境中是否仍然有效,在这种环境中种间相互作用可能会改变选择压力。在这里,我们证明,当受到结合T4P的噬菌体Luz19挑战时,铜绿假单胞菌通过IV型菌毛(T4P)的功能丧失突变进化出噬菌体抗性,并且即使在存在竞争性病原体USA300的情况下,这种进化轨迹也得以保留。通过抽动运动试验在表型上证实了噬菌体抗性,并通过全基因组测序在基因型上进行了证实。这些发现支持了种间竞争下噬菌体导向的稳健性,强调了其在管理复杂感染(如在囊性纤维化中所见的感染,其中微生物多样性是常态)方面的转化潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/12211013/b4ede3b4920f/spectrum.02882-24.f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/12211013/aa91fbc8328b/spectrum.02882-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/12211013/70e1942cc4e5/spectrum.02882-24.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/12211013/d1048989efaf/spectrum.02882-24.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/12211013/b4ede3b4920f/spectrum.02882-24.f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/12211013/aa91fbc8328b/spectrum.02882-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/12211013/70e1942cc4e5/spectrum.02882-24.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/12211013/d1048989efaf/spectrum.02882-24.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/12211013/b4ede3b4920f/spectrum.02882-24.f004.jpg

相似文献

[1]
Phage steering in the presence of a competing bacterial pathogen.

Microbiol Spectr. 2025-7

[2]
Horizontal Gene Transfer and CRISPR Targeting Drive Phage-Bacterial Host Interactions and Coevolution in "Pink Berry" Marine Microbial Aggregates.

Appl Environ Microbiol. 2023-7-26

[3]
Prophylactic phage biocontrol prevents infection in a quantitative model of bacterial virulence.

Appl Environ Microbiol. 2024-10-23

[4]
Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis.

Cochrane Database Syst Rev. 2017-4-25

[5]
Management of urinary stones by experts in stone disease (ESD 2025).

Arch Ital Urol Androl. 2025-6-30

[6]
Interventions for the eradication of meticillin-resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis.

Cochrane Database Syst Rev. 2022-12-13

[7]
Does Augmenting Irradiated Autografts With Free Vascularized Fibula Graft in Patients With Bone Loss From a Malignant Tumor Achieve Union, Function, and Complication Rate Comparably to Patients Without Bone Loss and Augmentation When Reconstructing Intercalary Resections in the Lower Extremity?

Clin Orthop Relat Res. 2025-6-26

[8]
and comparative analysis of 79 clinical isolates.

Microbiol Spectr. 2025-7

[9]
Distinct adaptation and epidemiological success of different genotypes within serovar Dublin.

Elife. 2025-6-25

[10]
The virulent bacteriophage Henu8 as an antimicrobial synergist against .

Microbiol Spectr. 2025-7

引用本文的文献

[1]
Phage Therapy: Combating Evolution of Bacterial Resistance to Phages.

Viruses. 2025-8-8

本文引用的文献

[1]
PlzR regulates type IV pili assembly in Pseudomonas aeruginosa via PilZ binding.

Nat Commun. 2024-10-8

[2]
surface motility and invasion into competing communities enhance interspecies antagonism.

mBio. 2024-9-11

[3]
The impact of phage and phage resistance on microbial community dynamics.

PLoS Biol. 2024-4

[4]
The type IV pilus chemoreceptor PilJ controls chemotaxis of one bacterial species towards another.

PLoS Biol. 2024-2

[5]
Inhibition of PQS signaling by the Pf bacteriophage protein PfsE enhances viral replication in Pseudomonas aeruginosa.

Mol Microbiol. 2024-1

[6]
Mechanisms of antibiotic resistance in biofilms.

Biofilm. 2023-5-2

[7]
Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics.

Signal Transduct Target Ther. 2022-6-25

[8]
Phage steering of antibiotic-resistance evolution in the bacterial pathogen, .

Evol Med Public Health. 2020-7-11

[9]
Community context matters for bacteria-phage ecology and evolution.

ISME J. 2021-11

[10]
The Building Blocks of Antimicrobial Resistance in : Implications for Current Resistance-Breaking Therapies.

Front Cell Infect Microbiol. 2021-4-16

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索