近日，以色列魏茨曼科学研究所Rotem Sorek及其小组揭示细菌通过甲基化的单核苷酸感知病毒诱导的基因组降解。这一研究成果于2026年7月9日发表在国际顶尖学术期刊《科学》上。

在这里，课题组描述了Metis，这是一种直接感知噬菌体介导的宿主基因组降解的细菌防御系统。Metis一旦检测到修饰的单核苷酸m6dAMP，就会终止噬菌体感染。当脱氧腺苷甲基化在DNA聚合物上不断发生时，m6dAMP的积累表明宿主基因组已经被降解。在I型Metis中，m6dAMP的感知激活NAD+二磷酸酶，导致NAD+耗竭并停止感染过程；而II型Metis的效应物是一种跨膜蛋白，其毒性是在对修饰的单核苷酸的反应中触发的。该课题组进一步表明，梅蒂斯的防御依赖于内源性DNA甲基化酶，并且噬菌体可以通过使宿主基因组降解失活的突变来逃避梅蒂斯。

据悉，噬菌体通常将其细菌宿主的基因组降解为单个核苷酸。

附：英文原文

Title: Bacteria sense virus-induced genome degradation via methylated mononucleotides

Author: Ilya Osterman, Bohdana Hurieva, Sarit Moses, Alla H. Falkovich, Maxim Itkin, Sergey Malitsky, Eliane Hadas Yardeni, Erez Yirmiya, Rotem Sorek

Issue&Volume: 2026-07-09

Abstract: Phages often degrade the genome of their bacterial host to individual nucleotides. Here we describe Metis, a bacterial defense system that directly senses phage-mediated host genome degradation. Metis aborts phage infection once it detects the modified mono-nucleotide m6dAMP. As methylation of deoxyadenosines usually occurs on the DNA polymer, accumulation of m6dAMP signals that the host genome has been degraded. In type I Metis, sensing of m6dAMP activates an NAD+ diphosphatase, leading to NAD+ depletion and cessation of the infection process; while the effector in type II Metis is a membrane-spanning protein whose toxicity is triggered in response to the modified mono-nucleotide. We further show that Metis defense depends on endogenous DNA methylases, and that phages can escape Metis via mutations that inactivate host genome degradation.

DOI: aed6782

Source: https://www.science.org/doi/10.1126/science.aed6782

期刊信息

Science：《科学》，创刊于1880年。隶属于美国科学促进会，最新IF：63.714

官方网址：https://www.sciencemag.org/

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