A jumbo phage that forms a nucleus-like structure evades CRISPR-Cas DNA targeting but is vulnerable to type III RNA-based immunity.,Nature Microbiology

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A jumbo phage that forms a nucleus-like structure evades CRISPR-Cas DNA targeting but is vulnerable to type III RNA-based immunity.
Nature Microbiology ( IF 20.5 ) Pub Date : 2019-12-09 , DOI: 10.1038/s41564-019-0612-5
Lucia M Malone ₁ , Suzanne L Warring ₁ , Simon A Jackson _{1,

2} , Carolin Warnecke _{1,

3} , Paul P Gardner _{2,

4} , Laura F Gumy ₅ , Peter C Fineran _{1,

2}

Affiliation

CRISPR-Cas systems provide bacteria with adaptive immunity against bacteriophages1. However, DNA modification2,3, the production of anti-CRISPR proteins4,5 and potentially other strategies enable phages to evade CRISPR-Cas. Here, we discovered a Serratia jumbo phage that evades type I CRISPR-Cas systems, but is sensitive to type III immunity. Jumbo phage infection resulted in a nucleus-like structure enclosed by a proteinaceous phage shell-a phenomenon only reported recently for distantly related Pseudomonas phages6,7. All three native CRISPR-Cas complexes in Serratia-type I-E, I-F and III-A-were spatially excluded from the phage nucleus and phage DNA was not targeted. However, the type III-A system still arrested jumbo phage infection by targeting phage RNA in the cytoplasm in a process requiring Cas7, Cas10 and an accessory nuclease. Type III, but not type I, systems frequently targeted nucleus-forming jumbo phages that were identified in global viral sequence datasets. The ability to recognize jumbo phage RNA and elicit immunity probably contributes to the presence of both RNA- and DNA-targeting CRISPR-Cas systems in many bacteria1,8. Together, our results support the model that jumbo phage nucleus-like compartments serve as a barrier to DNA-targeting, but not RNA-targeting, defences, and that this phenomenon is widespread among jumbo phages.

中文翻译：

形成核样结构的巨型噬菌体规避了CRISPR-Cas DNA靶向，但容易受到基于III型RNA的免疫。

CRISPR-Cas系统为细菌提供了针对噬菌体的适应性免疫力1。然而，DNA修饰2、3，抗CRISPR蛋白4、5的产生以及潜在的其他策略使噬菌体能够逃避CRISPR-Cas。在这里，我们发现了一种沙雷氏菌巨大的噬菌体，该噬菌体逃避了I型CRISPR-Cas系统，但对III型免疫很敏感。巨噬细胞感染导致被蛋白噬菌体壳包围的核样结构，这种现象最近才报道为远缘相关的假单胞菌噬菌体6,7。噬菌体类型IE，IF和III-A中的所有三种天然CRISPR-Cas复合物在空间上都被排除在噬菌体核之外，并且噬菌体DNA未被靶向。但是，在需要Cas7，Cas10和辅助核酸酶的过程中，III-A型系统仍然通过在细胞质中靶向噬菌体RNA来阻止巨噬细胞的感染。第三类但不是I型，系统通常针对的是在全局病毒序列数据集中识别出的形成核的巨型噬菌体。识别巨型噬菌体RNA和引发免疫的能力可能有助于在许多细菌中同时存在靶向RNA和DNA的CRISPR-Cas系统1,8。在一起，我们的结果支持该模型，即巨型噬菌体的核样区室可作为靶向DNA而非防御RNA的屏障，而这种现象在巨型噬菌体中很普遍。

更新日期：2019-12-11

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