膜结合核酸酶在基因组注射过程中直接切割噬菌体DNA，这一成果由麻省理工学院Michael T. Laub课题组经过不懈努力而取得。这一研究成果于2026年2月25日发表在国际顶尖学术期刊《自然》上。

小组描述了SNIPE，一种抗噬菌体防御系统，它组成部分定位于大肠杆菌的细菌细胞膜，以阻断噬菌体λ感染。使用放射性标记的噬菌体DNA和延时显微镜来跟踪噬菌体基因组，小组证明了SNIPE在基因组注射过程中直接切割噬菌体DNA。基于接近标记，该研究组发现SNIPE与λ基因组进入所必需的宿主蛋白和λ磁带测量蛋白结合，这有助于λ基因组穿过内膜注射。SNIPE也防御不同的虹吸病毒，可能是通过与它们的卷尺蛋白直接相互作用。他们的研究结果表明，SNIPE是一种广泛存在的细菌防御系统，它利用噬菌体基因组注射的空间组织特异性靶向病毒DNA，代表了一种在原核免疫系统中区分自我与非自我的先前未知的策略。

研究人员表示，从哺乳动物到细菌，病毒核酸的直接识别和切割是对抗病毒感染的有效防御策略，但它需要区分自我和非自我的机制。在细菌中，CRISPR-Cas和限制性修饰系统分别通过识别特定的DNA序列或DNA修饰来实现这种区分。其他机制可能还有待发现。

附：英文原文

Title: A membrane-bound nuclease directly cleaves phage DNA during genome injection

Author: Saxton, Daniel S., DeWeirdt, Peter C., Doering, Christopher R., Roney, Ian J., Laub, Michael T.

Issue&Volume: 2026-02-25

Abstract: From mammals to bacteria, the direct recognition and cleavage of viral nucleic acids is a potent defence strategy against viral infection, but it requires mechanisms for distinguishing self from non-self1,2. In bacteria, CRISPR–Cas and restriction-modification systems achieve this discrimination by recognizing specific DNA sequences or DNA modifications, respectively. Alternative mechanisms probably remain to be discovered. Here, we characterize SNIPE, an anti-bacteriophage defence system that constitutively localizes to the bacterial cell membrane in Escherichia coli to block phage λ infection. Using radiolabelled phage DNA and time-lapse microscopy to track phage genomes, we demonstrate that SNIPE directly cleaves phage DNA during genome injection. Based on proximity labelling, we find that SNIPE associates with host proteins essential for λ genome entry and with the λ tape measure protein, which facilitates λ genome injection across the inner membrane. SNIPE also defends against diverse siphoviruses, probably through direct interactions with their tape measure proteins. Our findings establish SNIPE as a widespread bacterial defence system that exploits the spatial organization of phage genome injection to specifically target viral DNA, representing a previously unknown strategy for distinguishing self from non-self in prokaryotic immune systems.

DOI: 10.1038/s41586-026-10207-1

Source: https://www.nature.com/articles/s41586-026-10207-1