Bacteriophage genes that inactivate the CRISPR/Cas bacterial immune system.

Bacteriophage genes that inactivate the CRISPR/Cas bacterial immune system.
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DOI:
10.1038/nature11723
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发表时间:
2013-01-17
期刊:
影响因子:
64.8
通讯作者:
Davidson AR
Davidson AR
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bondy-Denomy J;Pawluk A;Maxwell KL;Davidson AR

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细菌广泛使用的一种系统,用于保护潜在危险的外来DNA分子,由成簇的规则间隔短回文重复序列(CRISPR)与CAS(CRISPR相关)基因组成。类似于真核生物中的RNA干扰,这些CRISPR/Cas系统使用小RNA进行序列特异性检测和入侵基因组的中和。在这里,我们描述了调节CRISPR/Cas系统抑制的第一个基因例子。在感染铜绿假单胞菌的噬菌体基因组中发现了5个不同的“抗CRISPR”基因。噬菌体抗CRISPR基因的突变使其无法感染具有功能的CRISPR/Cas系统的细菌,而将相同基因添加到CRISPR/Cas靶向噬菌体的基因组中,使其能够避开CRISPR/Cas系统。噬菌体编码的抗CRISPR基因可能是噬菌体克服高度流行的CRISPR/Cas系统的一种广泛的机制。抗CRISPR基因的存在为阐明CRISPR/Cas的功能机制提供了新的途径,并为噬菌体和细菌的共同进化提供了新的视角。
A widespread system used by bacteria for protection against potentially dangerous foreign DNA molecules consists of the clustered regularly interspaced short palindromic repeats (CRISPR) coupled withcas(CRISPR-associated) genes. Similar to RNA interference in eukaryotes, these CRISPR/Cas systems use small RNAs for sequence-specific detection and neutralization of invading genomes. Here we describe the first examples of genes that mediate the inhibition of a CRISPR/Cas system. Five distinct ‘anti-CRISPR’ genes were found in the genomes of bacteriophages infectingPseudomonas aeruginosa. Mutation of the anti-CRISPR gene of a phage rendered it unable to infect bacteria with a functional CRISPR/Cas system, and the addition of the same gene to the genome of a CRISPR/Cas-targeted phage allowed it to evade the CRISPR/Cas system. Phage-encoded anti-CRISPR genes may represent a widespread mechanism for phages to overcome the highly prevalent CRISPR/Cas systems. The existence of anti-CRISPR genes presents new avenues for the elucidation of CRISPR/Cas functional mechanisms and provides new insight into the co-evolution of phages and bacteria.