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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Huan Pu & Yuxin Chen & Xinjun Zhao & Lunzhi Dai & Aiping Tong & Dongmei Tang & Qiang Chen & Yamei Yu, 2025. "A toxin-antitoxin system provides phage defense via DNA damage and repair," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58540-9
    DOI: 10.1038/s41467-025-58540-9
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    References listed on IDEAS

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    1. Jacob Bobonis & Karin Mitosch & André Mateus & Nicolai Karcher & George Kritikos & Joel Selkrig & Matylda Zietek & Vivian Monzon & Birgit Pfalz & Sarela Garcia-Santamarina & Marco Galardini & Anna Sue, 2022. "Bacterial retrons encode phage-defending tripartite toxin–antitoxin systems," Nature, Nature, vol. 609(7925), pages 144-150, September.
    2. Lee A. Uranga & Emigdio D. Reyes & Praveen L. Patidar & Lindsay N. Redman & Shelley L. Lusetti, 2017. "The cohesin-like RecN protein stimulates RecA-mediated recombinational repair of DNA double-strand breaks," Nature Communications, Nature, vol. 8(1), pages 1-11, August.
    3. Tong Zhang & Hedvig Tamman & Kyo Coppieters ’t Wallant & Tatsuaki Kurata & Michele LeRoux & Sriram Srikant & Tetiana Brodiazhenko & Albinas Cepauskas & Ariel Talavera & Chloe Martens & Gemma C. Atkins, 2022. "Direct activation of a bacterial innate immune system by a viral capsid protein," Nature, Nature, vol. 612(7938), pages 132-140, December.
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