Abstract：
Toxin-antitoxins (TAs) are prokaryotic two-gene systems composed of a toxin neutralized by an antitoxin. Toxin-antitoxin-chaperone (TAC) systems additionally include a SecB-like chaperone that stabilizes the antitoxin by recognizing its chaperone addiction (ChAD) element. TACs mediate antiphage defense, but the mechanisms of viral sensing and restriction are unexplored. We identify two Escherichia coli antiphage TAC systems containing host inhibition of growth (HigBA) and CmdTA TA modules, HigBAC and CmdTAC. HigBAC is triggered through recognition of the gpV major tail protein of phage λ. Chaperone HigC recognizes gpV and ChAD via analogous aromatic molecular patterns, with gpV outcompeting ChAD to trigger toxicity. For CmdTAC, the CmdT ADP-ribosyltransferase toxin modifies mRNA to halt protein synthesis and limit phage propagation. Finally, we establish the modularity of TACs by creating a hybrid broad-spectrum antiphage system combining the CmdTA TA warhead with a HigC chaperone phage sensor. Collectively, these findings reveal the potential of TAC systems in broad-spectrum antiphage defense.
摘要：
毒素-抗毒素（TA）是由抗毒素中和的毒素组成的原核双基因系统。毒素-抗毒素-伴侣(TAC)系统另外包括SecB样伴侣,其通过识别其伴侣成瘾(ChAD)元件来稳定抗毒素。TACs介导抗噬菌体防御，但是病毒感知和限制的机制尚未被探索。我们确定了两个含有宿主生长抑制（HigBA）和CmdTATA模块的大肠杆菌抗噬菌体TAC系统，HigBAC和CmdTAC。HigBAC是通过识别噬菌体λ的gpV主要尾部蛋白而触发的。分子伴侣HigC通过类似的芳香分子模式识别gpV和ChAD，gpV胜过ChAD引发毒性。对于CmdTAC，CmdTADP-核糖基转移酶毒素修饰mRNA以停止蛋白质合成并限制噬菌体繁殖。最后,我们通过创建混合广谱抗噬菌体系统来建立TACs的模块化，该系统将CmdTATA弹头与HigC伴侣噬菌体传感器相结合。总的来说，这些发现揭示了TAC系统在广谱抗噬菌体防御中的潜力。
