Widespread anti-CRISPR proteins in virulent bacteriophages inhibit a range of Cas9 proteins.

Widespread anti-CRISPR proteins in virulent bacteriophages inhibit a range of Cas9 proteins.
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DOI:
10.1038/s41467-018-05092-w
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发表时间:
2018-07-25
影响因子:
16.6
通讯作者:
Moineau S
Moineau S
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hynes AP;Rousseau GM;Agudelo D;Goulet A;Amigues B;Loehr J;Romero DA;Fremaux C;Horvath P;Doyon Y;Cambillau C;Moineau S

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CRISPR-Cas系统是细菌抗病毒系统,细菌病毒(噬菌体,CRISPR)可以携带抗CRISPR(Acr)蛋白以逃避免疫。Acrs还可以微调基于CRISPR的基因组编辑工具的活性。虽然Acr在能够在携带CRISPR的宿主中休眠的细菌中普遍存在,但它们的直系同源物仅在毒性细菌中很少观察到。在这里,我们确定AcrIIA 6,在33%的毒性嗜热链球菌噬菌体基因组编码的Acr。AcrIIA 6的X射线结构显示了该Acr家族特有的一些特征。我们比较了AcrIIA 6与其他Acr的活性,包括AcrIIA 5(也来自S.嗜热芽孢杆菌(thermophilus)),并表征它们对一系列CRISPR-Cas系统的有效性。最后,我们证明了来自S.嗜热芽孢杆菌抑制Cas9介导的人类细胞基因组编辑。一些细菌携带编码抗CRISPR(Acr)蛋白的基因,这些蛋白干扰细菌CRISPR-Cas系统的活性。在这里,Hynes等人描述了来自链球菌的一个新的Acr家族,并研究了其在基因组编辑应用中的潜力。
CRISPR-Cas systems are bacterial anti-viral systems, and bacterial viruses (bacteriophages, phages) can carry anti-CRISPR (Acr) proteins to evade that immunity. Acrs can also fine-tune the activity of CRISPR-based genome-editing tools. While Acrs are prevalent in phages capable of lying dormant in a CRISPR-carrying host, their orthologs have been observed only infrequently in virulent phages. Here we identify AcrIIA6, an Acr encoded in 33% of virulent Streptococcus thermophilus phage genomes. The X-ray structure of AcrIIA6 displays some features unique to this Acr family. We compare the activity of AcrIIA6 to those of other Acrs, including AcrIIA5 (also from S. thermophilus phages), and characterize their effectiveness against a range of CRISPR-Cas systems. Finally, we demonstrate that both Acr families from S. thermophilus phages inhibit Cas9-mediated genome editing of human cells. Some phages carry genes coding for anti-CRISPR (Acr) proteins that interfere with the activity of bacterial CRISPR-Cas systems. Here, Hynes et al. characterize a new Acr family from streptococcal phages and investigate its potential in genome-editing applications.
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