A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome.-猫眼课题宝

DOI：

10.1038/s41564-022-01219-4

发表时间：

2022-10

期刊：

Nature microbiology

影响因子：

28.3

通讯作者：

中科院分区：

生物学1区

文献类型：

作者：

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519451/

细菌和它们的病毒噬菌体之间古老而持续的共同进化之战，已经产生了复杂的免疫系统，包括限制修饰和CRISPR-Cas。许多额外的抗噬菌体系统已被确定使用计算方法的基础上的基因组共定位防御岛，但这些屏幕可能不是详尽无遗的。在这里，我们开发了一个实验选择方案不可知的基因组背景，以确定防御系统在71个不同的E。大肠杆菌菌株。我们的研究结果揭示了21个保守的防御系统，其中没有一个以前被检测到在防御岛中富集。此外，我们的工作表明，完整的原噬菌体和移动的遗传元件是E.大肠杆菌，防御系统通常在特定地点或热点进行。这些热点编码了数十个额外的未表征的防御系统候选者。我们的研究结果揭示了大肠杆菌抗病毒免疫的扩展景观。并为其他物种的防御系统作图提供了一种方法。在这里，作者使用71 E。大肠杆菌菌株产生一个fosmid库，该库通过实验测试抗噬菌体活性，并发现数十种新的候选防御系统，其中许多是在原噬菌体或移动的遗传元件上携带的。

The ancient, ongoing coevolutionary battle between bacteria and their viruses, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Many additional anti-phage systems have been identified using computational approaches based on genomic co-location within defence islands, but these screens may not be exhaustive. Here we developed an experimental selection scheme agnostic to genomic context to identify defence systems in 71 diverse E. coli strains. Our results unveil 21 conserved defence systems, none of which were previously detected as enriched in defence islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defence systems in E. coli, with defence systems typically carried in specific locations or hotspots. These hotspots encode dozens of additional uncharacterized defence system candidates. Our findings reveal an extended landscape of antiviral immunity in E. coli and provide an approach for mapping defence systems in other species. Here the authors use 71 E. coli strains to generate a fosmid library that is experimentally tested for anti-phage activity and find dozens of new candidate defence systems, many of which are carried on prophage or mobile genetic elements.