Viral SSB-bound ssDNA activates the bacterial anti-phage defense system DARNA

Abstract

To protect themselves against phage infection, bacteria employ diverse defense systems that are typically activated specifically upon infection. However, the mechanisms of activation and self versus non-self discrimination for most systems remain poorly understood. Here, we show that the bacterial immunity protein DARNA, once activated, cleaves a subset of host tRNAs, thereby inhibiting phage propagation. Although phages escape DARNA-mediated defense through mutations in the gene encoding single-stranded DNA-binding protein (SSB), we find that phage SSBs do not directly stimulate DARNA. Instead, DARNA is activated by single-stranded DNA presented by phage SSB, but not by the host SSB. The recognition of an endogenous nucleic acid signal promoted by a viral protein ensures that DARNA can detect and respond to a broad range of viruses while avoiding autoimmunity.

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BibTeX RIS

BibTeX

@article{puteikiene2026viral,
  title = {{Viral SSB-bound ssDNA activates the bacterial anti-phage defense system DARNA}},
  author = {Rugile Puteikiene and Christopher N. Vassallo and Arunas Silanskas and Jonas Juozapaitis and Inga Songailiene and Michael T. Laub and Giedrius Sasnauskas},
  journal = {Nature Communications},
  year = {2026},
  month = oct,
  doi = {10.1038/s41467-026-78638-y},
  url = {https://www.nature.com/articles/s41467-026-78638-y},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - Viral SSB-bound ssDNA activates the bacterial anti-phage defense system DARNA
AU  - Rugile Puteikiene
AU  - Christopher N. Vassallo
AU  - Arunas Silanskas
AU  - Jonas Juozapaitis
AU  - Inga Songailiene
AU  - Michael T. Laub
AU  - Giedrius Sasnauskas
PY  - 2026
DA  - 2026/10/16
JO  - Nature Communications
DO  - 10.1038/s41467-026-78638-y
UR  - https://www.nature.com/articles/s41467-026-78638-y
AB  - To protect themselves against phage infection, bacteria employ diverse defense systems that are typically activated specifically upon infection. However, the mechanisms of activation and self versus non-self discrimination for most systems remain poorly understood. Here, we show that the bacterial immunity protein DARNA, once activated, cleaves a subset of host tRNAs, thereby inhibiting phage propagation. Although phages escape DARNA-mediated defense through mutations in the gene encoding single-stranded DNA-binding protein (SSB), we find that phage SSBs do not directly stimulate DARNA. Instead, DARNA is activated by single-stranded DNA presented by phage SSB, but not by the host SSB. The recognition of an endogenous nucleic acid signal promoted by a viral protein ensures that DARNA can detect and respond to a broad range of viruses while avoiding autoimmunity.
SN  - 2041-1723
ER  -

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