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.
原创:十六点五 中山二院糖尿病足中心
糖尿病足中有一种类型令人十分头疼,就是老人、干性坏疽、十分疼痛(静息疼痛,每到晚上患者都痛得喊“妈”),其实这种病人就是由于糖尿病外周血管病变为主要病因导致的糖尿病足。
原创:十六点五 中山二院糖尿病足中心
糖尿病足是一种顽症,讲到底就是糖尿病人足部伤口难以愈合,而一般皮肤溃疡的愈合都是疤痕愈合,疤痕愈合最重要的原料就是胶原蛋白,因此,糖尿病足难以愈合最重要的直接原因就是在糖尿病的状态下,足部皮肤溃疡的胶原蛋白生成少、慢、质量差。
糖尿病足以变化多端,治疗效果差,治疗方法多而成为一种难治性疾病。经过近20年的反复临床摸索,我们中心逐步形成了一整套对于大部分糖尿病足都行之有效的局部治疗方法。
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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