CRISPR–Cas systems provide bacteria with adaptive immunity against phages and plasmids; however, pathways regulating their activity are not well defined. We recently developed a high-throughput genome-wide method (SorTn-seq) and used this to uncover CRISPR–Cas regulators. Here, we demonstrate that the widespread Rsm/Csr pathway regulates the expression of multiple CRISPR–Cas systems in Serratia (type I-E, I-F and III-A). The main pathway component, RsmA (CsrA), is an RNA-binding post-transcriptional regulator of carbon utilisation, virulence and motility. RsmA binds cas mRNAs and suppresses type I and III CRISPR–Cas interference in addition to adaptation by type I systems. Coregulation of CRISPR–Cas and flagella by the Rsm pathway allows modulation of adaptive immunity when changes in receptor availability would alter susceptibility to flagella-tropic phages. Furthermore, we show that Rsm controls CRISPR–Cas in other genera, suggesting conservation of this regulatory strategy. Finally, we identify genes encoding RsmA homologues in phages, which have the potential to manipulate the physiology of host bacteria and might provide an anti-CRISPR activity.

中文翻译：

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Rsm (Csr) 转录后调控通路协同控制多个 CRISPR-Cas 免疫系统

CRISPR–Cas 系统为细菌提供针对噬菌体和质粒的适应性免疫；然而，调节其活性的途径并没有明确定义。我们最近开发了一种高通量全基因组方法 (SorTn-seq)，并用它来发现 CRISPR-Cas 调节因子。在这里，我们证明广泛的 Rsm/Csr 通路调节沙雷氏菌（IE、IF 和 III-A 型）中多个 CRISPR-Cas 系统的表达。主要途径成分 RsmA (CsrA) 是碳利用、毒力和运动性的 RNA 结合转录后调节剂。RsmA 结合 cas mRNA 并抑制 I 型和 III 型 CRISPR–Cas 干扰以及 I 型系统的适应。当受体可用性的变化会改变对鞭毛嗜性噬菌体的易感性时，Rsm 途径对 CRISPR-Cas 和鞭毛的共调节允许调节适应性免疫。此外，我们表明 Rsm 在其他属中控制 CRISPR-Cas，表明这种调控策略的保守性。最后，我们鉴定了噬菌体中编码 RsmA 同源物的基因，这些基因有可能操纵宿主细菌的生理机能，并可能提供抗 CRISPR 活性。