The novel anti-phage system Shield co-opts an RmuC domain to mediate phage defense across Pseudomonas species.
The novel anti-phage system Shield co-opts an RmuC domain to mediate phage defense across Pseudomonas species.
复制标题
DOI：
10.1371/journal.pgen.1010784
复制
发表时间：
2023-06
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
竞争性细菌-噬菌体相互作用导致大量细菌防御系统的进化，阻止噬菌体繁殖。近年来，计算和生物信息学方法支撑了许多新型细菌防御系统的发现。抗噬菌体系统经常在称为防御岛的基因组基因座中一起编码。在这里，我们报告了一种新型抗噬菌体系统的鉴定和表征，我们将其称为“Shield”，它构成了假单胞菌防御武器库的一部分。 Shield 系统包含核心成分 ShdA，这是一种带有 RmuC 结构域的膜结合蛋白。单独产生 ShdA 的异源产物足以介导细菌针对多种噬菌体的免疫。我们证明 Shield 和 ShdA 赋予群体水平的免疫力，但它们也会降低转化效率。我们进一步表明，ShdA 同源物可以在体外降解 DNA，并且当在异源宿主中表达时，可以改变宿主染色体 DNA 的组织。使用比较基因组方法确定了 Shield 如何分为四种亚型，其中三种亚型含有额外的成分，在某些情况下可能会对 ShdA 的活性产生负面影响和/或提供额外的噬菌体防御线。总的来说，我们的结果确定了假单胞菌细菌免疫库中的一个新参与者，它表现出一种新的保护机制，并揭示了 RmuC 结构域在噬菌体防御中的作用。噬菌体施加的进化压力驱使细菌获得许多防御系统。最近的研究强调了这些系统的非凡多样性，揭示了细菌和真核免疫之间令人兴奋的联系。在这里，我们描述了一种在假单胞菌属物种中发现的新型抗噬菌体系统，名为 Shield。我们确定了几种盾亚型，它们都具有相同的核心组件，并描述了其作用模式。多重耐药细菌感染的病例不断增加，迫切需要开发替代疗法。噬菌体疗法是治疗导致囊性纤维化患者严重肺部感染的多重耐药铜绿假单胞菌菌株的特别相关的方法。详细了解细菌免疫和噬菌体对抗策略是支撑合理设计噬菌体疗法对抗疾病的重要一步。
Competitive bacteria-bacteriophage interactions have resulted in the evolution of a plethora of bacterial defense systems preventing phage propagation. In recent years, computational and bioinformatic approaches have underpinned the discovery of numerous novel bacterial defense systems. Anti-phage systems are frequently encoded together in genomic loci termed defense islands. Here we report the identification and characterisation of a novel anti-phage system, that we have termed Shield, which forms part of the Pseudomonas defensive arsenal. The Shield system comprises the core component ShdA, a membrane-bound protein harboring an RmuC domain. Heterologous production of ShdA alone is sufficient to mediate bacterial immunity against several phages. We demonstrate that Shield and ShdA confer population-level immunity and that they can also decrease transformation efficiency. We further show that ShdA homologues can degrade DNA in vitro and, when expressed in a heterologous host, can alter the organisation of the host chromosomal DNA. Use of comparative genomic approaches identified how Shield can be divided into four subtypes, three of which contain additional components that in some cases can negatively affect the activity of ShdA and/or provide additional lines of phage defense. Collectively, our results identify a new player within the Pseudomonas bacterial immunity arsenal that displays a novel mechanism of protection, and reveals a role for RmuC domains in phage defense. The evolutionary pressure exerted by bacteriophages has driven bacteria to acquire numerous defense systems. Recent studies have highlighted the extraordinary diversity of these systems, uncovering exciting links between bacterial and eukaryotic immunity. Here we describe a novel anti-phage system, named Shield, found within Pseudomonas species. We identify several Shield subtypes, all harboring the same core component, and describe its mode of action. The growing instance of multidrug-resistant bacterial infections urgently requires the development of alternative treatments. Phage therapy is a particularly pertinent approach to treat multi-drug resistant Pseudomonas aeruginosa strains causing severe lung infection in cystic fibrosis patients. A detailed understanding of bacterial immunity and phage counter-strategies is an essential step to underpin the rational design of phage therapy to fight disease.
登录
查看更多内容
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1126/science.aba0372
发表时间：
2020-08-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gao L;Altae-Tran H;Böhning F;Makarova KS;Segel M;Schmid-Burgk JL;Koob J;Wolf YI;Koonin EV;Zhang F
通讯作者：
Zhang F
影响因子：
16
作者：
Lau, Rebecca K.;Ye, Qiaozhen;Corbett, Kevin D.
通讯作者：
Corbett, Kevin D.
影响因子：
10.7
作者：
Nguyen LT;Schmidt HA;von Haeseler A;Minh BQ
通讯作者：
Minh BQ
DOI：
10.1126/science.aar4120
发表时间：
2018-03-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Doron S;Melamed S;Ofir G;Leavitt A;Lopatina A;Keren M;Amitai G;Sorek R
通讯作者：
Sorek R