Conditional tolerance of temperate phages via transcription-dependent CRISPR-Cas targeting.
Conditional tolerance of temperate phages via transcription-dependent CRISPR-Cas targeting.
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DOI：
10.1038/nature13637
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发表时间：
2014-10-30
期刊：
影响因子：
64.8
通讯作者：
Marraffini, Luciano A.
中科院分区：
文献类型：
--
作者：
Goldberg, Gregory W.;Jiang, Wenyan;Bikard, David;Marraffini, Luciano A.
免疫系统的一个基本特征是能够区分病原体与自身和免疫因素，并攻击前者但容忍后者。Propylene CRISPR-Cas免疫系统使用Cas核酸酶和小RNA向导来防御噬菌体感染，所述小RNA向导指定用于切割病毒基因组的一个或多个靶位点。温带假丝酵母是可以整合到细菌染色体中的病毒，它们可以携带为溶原宿主提供适应性优势的基因。然而，严格依赖于DNA序列识别的CRISPR-Cas靶向通过温和噬菌体对裂解性和溶原性感染提供了不加选择的免疫力，从而完全损害了这些潜在有益元素的遗传稳定性。在这里，我们表明表皮葡萄球菌CRISPR-Cas系统可以防止溶解性感染，但耐受温和的细菌的溶原化。条件耐受性通过转录依赖性DNA靶向实现，并确保在诱导前噬菌体裂解周期后恢复靶向。我们的研究结果为CRISPR-Cas系统的功能差异提供了证据，并强调了靶向机制多样性的重要性。此外，他们将“对非自身的耐受性”的概念扩展到适应性免疫的原核分支。
A fundamental feature of immune systems is the ability to distinguish pathogenic from self and commensal elements, and to attack the former but tolerate the latter. Prokaryotic CRISPR-Cas immune systems defend against phage infection using Cas nucleases and small RNA guides that specify one or more target sites for cleavage of the viral genome. Temperate phages are viruses that can integrate into the bacterial chromosome, and they can carry genes that provide a fitness advantage to the lysogenic host. However, CRISPR-Cas targeting that relies strictly on DNA sequence recognition provides indiscriminate immunity to both lytic and lysogenic infection by temperate phages—compromising the genetic stability of these potentially beneficial elements altogether. Here we show that the Staphylococcus epidermidis CRISPR-Cas system can prevent lytic infection but tolerate lysogenization by temperate phages. Conditional tolerance is achieved through transcription-dependent DNA targeting, and ensures that targeting is resumed upon induction of the prophage lytic cycle. Our results provide evidence for the functional divergence of CRISPR-Cas systems and highlight the importance of targeting mechanism diversity. In addition, they extend the concept of ‘tolerance to non-self’ to the prokaryotic branch of adaptive immunity.
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DOI：
10.1126/science.1165771
发表时间：
2008-12-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Marraffini LA;Sontheimer EJ
通讯作者：
Sontheimer EJ
影响因子：
56.9
作者：
Jinek, Martin;Chylinski, Krzysztof;Charpentier, Emmanuelle
通讯作者：
Charpentier, Emmanuelle
影响因子：
3.2
作者：
Deveau, Helene;Barrangou, Rodolphe;Moineau, Sylvain
通讯作者：
Moineau, Sylvain
DOI：
10.1126/science.1159689
发表时间：
2008-08-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Brouns SJ;Jore MM;Lundgren M;Westra ER;Slijkhuis RJ;Snijders AP;Dickman MJ;Makarova KS;Koonin EV;van der Oost J
通讯作者：
van der Oost J
影响因子：
3.2
作者：
Hatoum-Aslan, Asma;Maniv, Inbal;Marraffini, Luciano A.
通讯作者：
Marraffini, Luciano A.