Cyclic-oligonucleotide-based anti-phage signalling systems (CBASS) are a family of defence systems against bacteriophages (hereafter phages) that share ancestry with the cGAS–STING innate immune pathway in animals. CBASS systems are composed of an oligonucleotide cyclase, which generates signalling cyclic oligonucleotides in response to phage infection, and an effector that is activated by the cyclic oligonucleotides and promotes cell death. Cell death occurs before phage replication is completed, therefore preventing the spread of phages to nearby cells. Here, we analysed 38,000 bacterial and archaeal genomes and identified more than 5,000 CBASS systems, which have diverse architectures with multiple signalling molecules, effectors and ancillary genes. We propose a classification system for CBASS that groups systems according to their operon organization, signalling molecules and effector function. Four major CBASS types were identified, sharing at least six effector subtypes that promote cell death by membrane impairment, DNA degradation or other means. We observed evidence of extensive gain and loss of CBASS systems, as well as shuffling of effector genes between systems. We expect that our classification and nomenclature scheme will guide future research in the developing CBASS field.

基于环状寡核苷酸的抗噬菌体信号系统 (CBASS) 是一个针对噬菌体（以下简称噬菌体）的防御系统家族，这些噬菌体与动物的 cGAS-STING 先天免疫通路具有相同的祖先。CBASS 系统由寡核苷酸环化酶和效应物组成，寡核苷酸环化酶响应噬菌体感染产生信号循环寡核苷酸，以及被环状寡核苷酸激活并促进细胞死亡的效应物。细胞死亡发生在噬菌体复制完成之前，因此阻止了噬菌体向附近细胞的扩散。在这里，我们分析了 38,000 个细菌和古菌基因组，并确定了 5,000 多个 CBASS 系统，这些系统具有多种结构，具有多种信号分子、效应子和辅助基因。我们为 CBASS 提出了一个分类系统，该系统根据其操纵子组织、信号分子和效应子功能对系统进行分组。确定了四种主要的 CBASS 类型，共享至少 6 种通过膜损伤、DNA 降解或其他方式促进细胞死亡的效应子亚型。我们观察到 CBASS 系统广泛获得和损失的证据，以及系统之间效应基因的改组。我们希望我们的分类和命名方案将指导未来 CBASS 领域的研究。以及系统之间效应基因的改组。我们希望我们的分类和命名方案将指导未来 CBASS 领域的研究。以及系统之间效应基因的改组。我们希望我们的分类和命名方案将指导未来 CBASS 领域的研究。