Prokaryotic antiviral defence systems are frequently toxic for host cells and stringent regulation is required to ensure survival and fitness. These systems must be readily available in case of infection but tightly controlled to prevent activation of an unnecessary cellular response. Here we investigate how the bacterial cyclic oligonucleotide-based antiphage signalling system (CBASS) uses its intrinsic protein modification system to regulate the nucleotide cyclase. By integrating a type II CBASS system from Bacillus cereus into the model organism Bacillus subtilis, we show that the protein-conjugating Cap2 (CBASS associated protein 2) enzyme links the cyclase exclusively to the conserved phage shock protein A (PspA) in the absence of phage. The cyclase–PspA conjugation is reversed by the deconjugating isopeptidase Cap3 (CBASS associated protein 3). We propose a model in which the cyclase is held in an inactive state by conjugation to PspA in the absence of phage, with conjugation released upon infection, priming the cyclase for activation.

原核抗病毒防御系统通常对宿主细胞有毒，需要严格调节以确保生存和适应。这些系统必须在感染时随时可用，但必须受到严格控制，以防止激活不必要的细胞反应。在这里，我们研究细菌基于环状寡核苷酸的抗噬菌体信号系统（CBASS）如何利用其内在蛋白质修饰系统来调节核苷酸环化酶。通过将来自蜡样芽孢杆菌的 II 型 CBASS 系统整合到模型生物枯草芽孢杆菌中，我们发现蛋白质缀合 Cap2（CBASS 相关蛋白 2）酶在没有噬菌体。环化酶-PspA 缀合可被解缀合肽酶 Cap3（CBASS 相关蛋白 3）逆转。我们提出了一种模型，其中环化酶在没有噬菌体的情况下通过与 PspA 缀合而保持在非活性状态，并且在感染时释放缀合，从而启动环化酶的激活。