CRISPR-Cas systems are adaptive immune systems that protect bacteria from bacteriophage (phage) infection1. To provide immunity, RNA-guided protein surveillance complexes recognize foreign nucleic acids, triggering their destruction by Cas nucleases2. While the essential requirements for immune activity are well understood, the physiological cues that regulate CRISPR-Cas expression are not. Here, a forward genetic screen identifies a two-component system (KinB-AlgB), previously characterized in the regulation of Pseudomonas aeruginosa alginate biosynthesis3,4, as a regulator of the expression and activity of the P. aeruginosa Type I-F CRISPR-Cas system. Downstream of KinB-AlgB, activators of alginate production AlgU (a σE orthologue) and AlgR repress CRISPR-Cas activity during planktonic and surface-associated growth5. AmrZ, another alginate regulator6, is triggered to repress CRISPR-Cas immunity upon surface association. Pseudomonas phages and plasmids have taken advantage of this regulatory scheme and carry hijacked homologs of AmrZ that repress CRISPR-Cas expression and activity. This suggests that while CRISPR-Cas regulation may be important to limit self-toxicity, endogenous repressive pathways represent a vulnerability for parasite manipulation.

中文翻译：

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细菌藻酸盐调节剂和噬菌体同源物抑制CRISPR-Cas免疫力。

CRISPR-Cas系统是适应性免疫系统，可保护细菌免受噬菌体（噬菌体）感染1。为了提供免疫力，RNA引导的蛋白质监视复合物可识别外来核酸，触发其被Cas核酸酶破坏2。尽管人们对免疫活性的基本要求已广为人知，但调节CRISPR-Cas表达的生理学线索却并非如此。在此，前向遗传筛选确定了以前以铜绿假单胞菌藻酸盐生物合成3,4的调节为特征的两组分系统（KinB-AlgB），作为铜绿假单胞菌IF型CRISPR-Cas系统的表达和活性的调节剂。 。在KinB-AlgB下游，藻酸盐生产AlgU（σE直系同源物）和AlgR的激活剂在浮游和表面相关生长过程中抑制CRISPR-Cas活性5。AmrZ，另一个藻酸盐调节剂6，在表面缔合后被触发抑制CRISPR-Cas免疫。假单胞菌噬菌体和质粒已经利用了这种调节方案，并携带了劫持的AmrZ同源物，从而抑制了CRISPR-Cas的表达和活性。这表明，尽管CRISPR-Cas调控对限制自身毒性可能很重要，但内源性抑制途径代表了寄生虫操纵的脆弱性。