当前位置: X-MOL 学术Nucleic Acids Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The phage defence island of a multidrug resistant plasmid uses both BREX and type IV restriction for complementary protection from viruses
Nucleic Acids Research ( IF 16.6 ) Pub Date : 2021-09-23 , DOI: 10.1093/nar/gkab906
David M Picton 1 , Yvette A Luyten 2 , Richard D Morgan 2 , Andrew Nelson 3 , Darren L Smith 3 , David T F Dryden 1 , Jay C D Hinton 4 , Tim R Blower 1
Affiliation  

Bacteria have evolved a multitude of systems to prevent invasion by bacteriophages and other mobile genetic elements. Comparative genomics suggests that genes encoding bacterial defence mechanisms are often clustered in ‘defence islands’, providing a concerted level of protection against a wider range of attackers. However, there is a comparative paucity of information on functional interplay between multiple defence systems. Here, we have functionally characterised a defence island from a multidrug resistant plasmid of the emerging pathogen Escherichia fergusonii. Using a suite of thirty environmentally-isolated coliphages, we demonstrate multi-layered and robust phage protection provided by a plasmid-encoded defence island that expresses both a type I BREX system and the novel GmrSD-family type IV DNA modification-dependent restriction enzyme, BrxU. We present the structure of BrxU to 2.12 Å, the first structure of the GmrSD family of enzymes, and show that BrxU can utilise all common nucleotides and a wide selection of metals to cleave a range of modified DNAs. Additionally, BrxU undergoes a multi-step reaction cycle instigated by an unexpected ATP-dependent shift from an intertwined dimer to monomers. This direct evidence that bacterial defence islands can mediate complementary layers of phage protection enhances our understanding of the ever-expanding nature of phage-bacterial interactions.

中文翻译:

多重耐药质粒的噬菌体防御岛同时使用 BREX 和 IV 型限制来互补保护免受病毒侵害

细菌已经进化出多种系统来防止噬菌体和其他移动遗传元件的入侵。比较基因组学表明,编码细菌防御机制的基因通常聚集在“防御岛”中,为更广泛的攻击者提供一致的保护水平。然而,关于多种防御系统之间功能相互作用的信息相对缺乏。在这里,我们从新出现的病原体弗格氏埃希氏菌的多重耐药质粒中对防御岛进行了功能表征。使用一套 30 个环境隔离的大肠杆菌噬菌体,我们展示了由质粒编码的防御岛提供的多层和强大的噬菌体保护,该防御岛同时表达 I 型 BREX 系统和新型 GmrSD 家族 IV 型 DNA 修饰依赖性限制酶,BrxU。我们将 BrxU 的结构呈现为 2.12 Å,这是 GmrSD 酶家族的第一个结构,并表明 BrxU 可以利用所有常见的核苷酸和多种金属来切割一系列修饰的 DNA。此外,BrxU 经历了一个多步骤的反应循环,这是由一个意外的 ATP 依赖性转变引发的,从交织的二聚体转变为单体。这一直接证据表明,细菌防御岛可以介导噬菌体保护的互补层,增强了我们对噬菌体-细菌相互作用不断扩大的性质的理解。BrxU 经历了一个多步骤的反应循环,这是由一个意外的 ATP 依赖性转变引发的,从交织的二聚体转变为单体。这一直接证据表明,细菌防御岛可以介导噬菌体保护的互补层,增强了我们对噬菌体-细菌相互作用不断扩大的性质的理解。BrxU 经历了一个多步骤的反应循环,这是由一个意外的 ATP 依赖性转变引发的,从交织的二聚体转变为单体。这一直接证据表明,细菌防御岛可以介导噬菌体保护的互补层,增强了我们对噬菌体-细菌相互作用不断扩大的性质的理解。
更新日期:2021-09-23
down
wechat
bug