Li Yuping,1,7,* Linlin Guan,2 Isabelle Becher,3 Kira S. Makarova,4 Xueli Cao,2 Surabhi Hareendranath,1 Jingwen Guan,1 Frank Stein,3 Siqi Yang,2 Arne Boergel,3 Karine Lapouge,3 Kim Remans,3 David Agard,5 Mikhail Savitski,3 Athanasios Typas,3 Eugene V. Koonin,4 Yue Feng,2,* and Joseph Bondy-Denomy1,6,8,*
1 Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94403, USA
2 State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
3 European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany
4 Computational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
5 The Chan-Zuckerberg Institute for Advanced Biological Imaging and the Department of Biochemistry, University of California, San Francisco, San Francisco, CA 94143, USA
6 Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94403, USA
7 Present address: Biozentrum, University of Basel, Basel 4056, Switzerland
8 Lead contact
*Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (L.Y.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (Y.F.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J.B.-D.)
https://doi.org/10.1016/j.cell.2025.02.016
SUMMARY
Jumbo bacteriophages of the fKZ-like family assemble a lipid-based early phage infection (EPI) vesicle and a proteinaceous nucleus-like structure during infection. These structures protect the phage from nucleases and may create selective pressure for immunity mechanisms targeting this specific phage family. Here, we identify ‘‘jumbo phage killer’’ (Juk), a two-component immune system that terminates infection of fKZ-like phages, suppressing the expression of early phage genes and preventing phage DNA replication and phage nucleus assembly while saving the cell. JukA (formerly YaaW) rapidly senses the EPI vesicle by binding to an early-expressed phage protein, gp241, and then directly recruits JukB. The JukB effector structurally resembles a pore-forming toxin and destabilizes the EPI vesicle. Functional anti-fKZ JukA homologs are found across bacterial phyla, associated with diverse effectors. These findings reveal a widespread defense system that specifically targets early events executed by fKZ-like jumbo phages prior to phage nucleus assembly.
慢伤前沿 中诺医疗
糖尿病是北美第六大死亡原因。糖尿病人中有25%会发生足溃疡，而足溃疡会显著增加截肢风险和死亡率。早期识别高危足和给予及时治疗可以挽救下肢和生命。多学科治疗方法对于支持患者需求至关重要。
伤口世界平台生态圈，以“关爱人间所有伤口患者”为愿景，连接、整合和拓展线上和线下的管理慢性伤口的资源，倡导远程、就近和居家管理慢性伤口，解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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