美国洛克菲勒大学Luciano A. Marraffini和美国芝加哥大学Phoebe A. Rice共同合作，近期取得重要工作进展。他们研究提出，DNA糖基化酶为原核生物提供抗病毒能力。相关研究成果2024年4月17日在线发表于《自然》杂志上。

据介绍，细菌通过演化出各种各样的防御系统来适应噬菌体的捕食。尽管可以使用生物信息学工具鉴定抗噬菌体免疫基因，但新系统的发现仅限于可用的原核序列数据。

为了克服这一限制，研究人员用裂解大肠杆菌噬菌体T4感染携带土壤宏基因组DNA文库的大肠杆菌，以分离携带保护基因的克隆。按照这种方法，研究人员鉴定了Brig1，这是一种DNA糖苷酶，它从噬菌体T4基因组中切割α-葡糖基-羟甲基胞嘧啶核碱基，产生碱基位点并抑制病毒复制。Brig1同源物可提供对T-even噬菌体的免疫力，存在于不同细菌分支的多个噬菌体防御基因座中。

总之，这一研究强调了筛选未测序DNA的好处，并揭示了原核DNA糖基化酶是细菌-噬菌体军备竞赛中的重要参与者。

附：英文原文

Title: DNA glycosylases provide antiviral defence in prokaryotes

Author: Hossain, Amer A., Pigli, Ying Z., Baca, Christian F., Heissel, Sren, Thomas, Alexis, Libis, Vincent K., Burian, Jn, Chappie, Joshua S., Brady, Sean F., Rice, Phoebe A., Marraffini, Luciano A.

Issue&Volume: 2024-04-17

Abstract: Bacteria have adapted to phage predation by evolving a vast assortment of defence systems1. Although anti-phage immunity genes can be identified using bioinformatic tools, the discovery of novel systems is restricted to the available prokaryotic sequence data2. Here, to overcome this limitation, we infected Escherichia coli carrying a soil metagenomic DNA library3 with the lytic coliphage T4 to isolate clones carrying protective genes. Following this approach, we identified Brig1, a DNA glycosylase that excises α-glucosyl-hydroxymethylcytosine nucleobases from the bacteriophage T4 genome to generate abasic sites and inhibit viral replication. Brig1 homologues that provide immunity against T-even phages are present in multiple phage defence loci across distinct clades of bacteria. Our study highlights the benefits of screening unsequenced DNA and reveals prokaryotic DNA glycosylases as important players in the bacteria–phage arms race.

DOI: 10.1038/s41586-024-07329-9

Source: https://www.nature.com/articles/s41586-024-07329-9