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一种噬菌体的发现解释了人类疾病的一个关键决定因素。

The discovery of a phage explains a key determinant of human disease.

作者信息

Nicholson Beth, Santé José F, Chaney Elizabeth H, Deme Justin C, Deecker Shayna R, Sztanko Kristina, Davidson Alan R, Lea Susan M, Ensminger Alexander W

机构信息

Department of Biochemistry, University of Toronto, 661 University Ave., Toronto, Ontario M5G 1M1, Canada.

Department of Molecular Genetics, University of Toronto, 661 University Ave., Toronto, Ontario M5G 1M1, Canada.

出版信息

Sci Adv. 2025 Sep 5;11(36):eadx9722. doi: 10.1126/sciadv.adx9722. Epub 2025 Sep 3.

DOI:10.1126/sciadv.adx9722
PMID:40901954
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12407071/
Abstract

Host cells provide intracellular bacteria with protection from harsh environmental conditions and immune responses, but for many intracellular pathogens, this protection does not appear to be absolute as once thought. Bacteriophages that can kill bacteria inside host cells have been identified for pathogens including , , and species. Even in pathogens for which no stable phages have been isolated, such as , the presence of phage defense systems suggests phage susceptibility. Here, we report the stable isolation of bacteriophage LME-1 ( mobile element-1) and its impact on bacterial virulence in humans. Cryo-electron microscopy of the capsid (2.1 angstroms) and portal-tail complex (1.9 angstroms) reveals an unambiguous phage particle with T7-like morphology. Characterizing the host range of this phage, we make a serendipitous finding that links the acquisition of a phage defense mechanism to the formation of a virulent clade of responsible for 80% of all Legionnaires' disease.

摘要

宿主细胞为细胞内细菌提供保护,使其免受恶劣环境条件和免疫反应的影响,但对于许多细胞内病原体而言,这种保护似乎并不像曾经认为的那样绝对。已经针对包括、和物种在内的病原体鉴定出了能够杀死宿主细胞内细菌的噬菌体。即使在尚未分离出稳定噬菌体的病原体中,如,噬菌体防御系统的存在也表明其对噬菌体敏感。在这里,我们报告了噬菌体LME-1(移动元件-1)的稳定分离及其对人类细菌毒力的影响。衣壳(2.1埃)和门户-尾部复合体(1.9埃)的冷冻电子显微镜显示出具有T7样形态的明确噬菌体颗粒。在表征这种噬菌体的宿主范围时,我们偶然发现了一种噬菌体防御机制的获得与导致80%军团病的毒力进化枝的形成之间的联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7164/12407071/7663ed0cbb6c/sciadv.adx9722-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7164/12407071/39f0da983a54/sciadv.adx9722-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7164/12407071/bbd534f1a23e/sciadv.adx9722-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7164/12407071/5ef2ca3678f6/sciadv.adx9722-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7164/12407071/611e01b6d7d2/sciadv.adx9722-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7164/12407071/eb1c5d9bc9f6/sciadv.adx9722-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7164/12407071/7663ed0cbb6c/sciadv.adx9722-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7164/12407071/39f0da983a54/sciadv.adx9722-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7164/12407071/bbd534f1a23e/sciadv.adx9722-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7164/12407071/5ef2ca3678f6/sciadv.adx9722-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7164/12407071/611e01b6d7d2/sciadv.adx9722-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7164/12407071/eb1c5d9bc9f6/sciadv.adx9722-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7164/12407071/7663ed0cbb6c/sciadv.adx9722-f6.jpg

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本文引用的文献

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EMDB-the Electron Microscopy Data Bank.电子显微镜数据银行(EMDB)。
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Structural Study of the Cobetia marina Bacteriophage 1 (Carin-1) by Cryo-EM.利用冷冻电镜技术对海洋杆菌噬菌体 1(Carin-1)进行结构研究。
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Mobile Element Integration Reveals a Chromosome Dimer Resolution System in .移动元件的整合揭示了. 中的染色体二聚体解析系统。
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