Bacteria and their viruses (bacteriophages or phages) are engaged in an intense evolutionary arms race^1,2,3,4,5. While the mechanisms of many bacterial antiphage defence systems are known¹, how these systems avoid toxicity outside infection yet activate quickly after infection is less well understood. Here we show that the bacterial phage anti-restriction-induced system (PARIS) operates as a toxin–antitoxin system, in which the antitoxin AriA sequesters and inactivates the toxin AriB until triggered by the T7 phage counterdefence protein Ocr. Using cryo-electron microscopy, we show that AriA is related to SMC-family ATPases but assembles into a distinctive homohexameric complex through two oligomerization interfaces. In uninfected cells, the AriA hexamer binds to up to three monomers of AriB, maintaining them in an inactive state. After Ocr binding, the AriA hexamer undergoes a structural rearrangement, releasing AriB and allowing it to dimerize and activate. AriB is a toprim/OLD-family nuclease, the activation of which arrests cell growth and inhibits phage propagation by globally inhibiting protein translation through specific cleavage of a lysine tRNA. Collectively, our findings reveal the intricate molecular mechanisms of a bacterial defence system triggered by a phage counterdefence protein, and highlight how an SMC-family ATPase has been adapted as a bacterial infection sensor.

细菌及其病毒（噬菌体或噬菌体）正在进行激烈的进化军备竞赛^1,2,3,4,5 。虽然许多细菌反噬菌体防御系统的机制是已知的¹ ，但这些系统如何避免感染外的毒性并在感染后快速激活尚不清楚。在这里，我们展示了细菌噬菌体抗限制性诱导系统（PARIS）作为毒素-抗毒素系统发挥作用，其中抗毒素AriA隔离毒素AriB并使毒素AriB失活，直到被T7噬菌体反防御蛋白Ocr触发。使用冷冻电子显微镜，我们发现 AriA 与 SMC 家族 ATP 酶相关，但通过两个寡聚界面组装成独特的同源六聚体复合物。在未感染的细胞中，AriA 六聚体与最多三个 AriB 单体结合，使它们保持非活性状态。 Ocr 结合后，AriA 六聚体发生结构重排，释放 AriB 并使其二聚化并激活。 AriB 是一种 toprim/OLD 家族核酸酶，其激活可通过赖氨酸 tRNA 的特异性裂解全局抑制蛋白质翻译，从而阻止细胞生长并抑制噬菌体繁殖。总的来说，我们的研究结果揭示了噬菌体反防御蛋白触发的细菌防御系统的复杂分子机制，并强调了 SMC 家族 ATP 酶如何适应细菌感染传感器。