欧洲分子生物学实验室（EMBL）Joseph Bondy-Denomy课题组取得一项新突破。他们报道了巨型噬菌体杀伤免疫系统以早期感染成核噬菌体为目标。这一研究成果于2025年3月19日发表在国际顶尖学术期刊《细胞》上。

该团队发现了“巨型噬菌体杀手”（Juk），这是一种双组分免疫系统，可以终止KZ样噬菌体的感染，抑制早期噬菌体基因的表达，阻止噬菌体DNA复制和噬菌体核组装，同时拯救细胞。JukA（以前称为YaaW）通过结合早期表达的噬菌体蛋白gp241快速感知EPI囊泡，然后直接招募JukB。JukB效应物在结构上类似于成孔毒素并破坏EPI囊泡的稳定性。功能性反KZ JukA同源物在细菌门中被发现，与不同的效应物相关。这些发现揭示了一个广泛的防御系统，它专门针对噬菌体核体组装之前由KZ样巨型噬菌体执行的早期事件。

据悉，KZ-like家族的巨型噬菌体在感染过程中聚集了一个基于脂质的早期噬菌体感染（EPI）囊泡和一个蛋白乙酰核样结构。这些结构保护噬菌体免受核酸酶的侵害，并可能为针对该特定噬菌体家族的免疫机制产生选择性压力。

附：英文原文

Title: Jumbo phage killer immune system targets early infection of nucleus-forming phages

Author: Li Yuping, Linlin Guan, Isabelle Becher, Kira S. Makarova, Xueli Cao, Surabhi Hareendranath, Jingwen Guan, Frank Stein, Siqi Yang, Arne Boergel, Karine Lapouge, Kim Remans, David Agard, Mikhail Savitski, Athanasios Typas, Eugene V. Koonin, Yue Feng, Joseph Bondy-Denomy

Issue&Volume: 2025-03-19

Abstract: Jumbo bacteriophages of the KZ-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 KZ-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-KZ 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 KZ-like jumbo phages prior to phage nucleus assembly.

DOI: 10.1016/j.cell.2025.02.016

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00201-6