A toxin-antitoxin system provides phage defense via DNA damage and repair

Huan Pu, Yuxin Chen, Xinjun Zhao, Lunzhi Dai, Aiping Tong, Dongmei Tang (), Qiang Chen () and Yamei Yu ()
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Huan Pu: Sichuan University
Yuxin Chen: Sichuan University
Xinjun Zhao: Sichuan University
Lunzhi Dai: Sichuan University
Aiping Tong: Sichuan University
Dongmei Tang: Sichuan University
Qiang Chen: Sichuan University
Yamei Yu: Sichuan University

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract Widespread in bacteria and archaea, toxin-antitoxin (TA) systems have been recently demonstrated to function in phage defense. Here we characterize the anti-phage function of a type IV TA system, ShosTA. Using structural and biochemical approaches, we show that ShosT couples phosphoribosyltransferase and pyrophosphatase activities to disrupt purine metabolism, resulting in DNA duplication, cell filamentation and ultimate cell death. ShosA binds DNA and likely recruits other proteins to facilitate DNA homologous recombination to antagonize ShosT’s toxicity. We identify Gp0.7 of T7 phage as a trigger for ShosTA system via shutting off the protein synthesis, and the C-terminus-mediated intrinsic instability of ShosA releases the toxicity of the existing ShosT proteins. Collectively, our results provide a novel toxin-antitoxin mechanism for anti-phage immunity and shed light on the triggering of this TA system.

Date: 2025
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DOI: 10.1038/s41467-025-58540-9

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