Bacteriophage Cooperation Suppresses CRISPR-Cas3 and Cas9 Immunity.

Bacteriophage Cooperation Suppresses CRISPR-Cas3 and Cas9 Immunity.
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DOI:
10.1016/j.cell.2018.06.013
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发表时间:
2018-08-09
期刊:
影响因子:
64.5
通讯作者:
Bondy-Denomy J
Bondy-Denomy J
中科院分区:
生物学1区
文献类型:
--
作者:
Borges AL;Zhang JY;Rollins MF;Osuna BA;Wiedenheft B;Bondy-Denomy J

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细菌利用CRISPR-Cas适应性免疫系统来保护免受噬菌体(CRISPR)的侵害,并且一些CRISPR产生抑制免疫功能的抗CRISPR(Acr)蛋白。尽管有一些Acr蛋白的全面机制和结构信息,但它们在感染期间如何被噬菌体部署和利用是未知的。在这里,我们表明,当面对CRISPR-Cas免疫时,Acr生产并不能保证噬菌体复制,而是当噬菌体群体数量低于临界阈值时,感染失败。只有当多个噬菌体基因组对单个细胞贡献足够的Acr剂量时,感染才成功。不能复制的噬菌体基因组产生的Acr蛋白使细胞免疫抑制,这使细胞易于被群体中的其他细菌成功感染。CRISPR-Cas抑制的这种利他机制证明了病毒间的合作,这种合作也可能表现在其他宿主-寄生虫相互作用中。免疫宿主的CRISPR抗性和感染需要临界阈值水平的噬菌体抗CRISPR蛋白,这表明抗CRISPR系统可能在多次或连续感染的可能性高的条件下进化。
Bacteria utilize CRISPR-Cas adaptive immune systems for protection from bacteriophages (phages), and some phages produce anti-CRISPR (Acr) proteins that inhibit immune function. Despite thorough mechanistic and structural information for some Acr proteins, how they are deployed and utilized by a phage during infection is unknown. Here, we show that Acr production does not guarantee phage replication when faced with CRISPR-Cas immunity, but instead, infections fail when phage population numbers fall below a critical threshold. Infections succeed only if a sufficient Acr dose is contributed to a single cell by multiple phage genomes. The production of Acr proteins by phage genomes that fail to replicate leave the cell immunosuppressed, which predisposes the cell for successful infection by other phages in the population. This altruistic mechanism for CRISPR-Cas inhibition demonstrates inter-virus cooperation that may also manifest in other host-parasite interactions. A critical threshold level of phage anti-CRISPR proteins is required for CRISPR resistance and infection of immune hosts, suggesting that anti-CRISPR systems may have evolved under conditions where the likelihood of multiple or sequential infection is high.
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作者:
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