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Peer-reviewedCC BYCell Host & Microbe

YprA-family helicases provide the missing link between diverse prokaryotic immune systems

  • Ryan T. Bell1,2
  • Thomas Gaudin3,4
  • Yi Wu5,6
  • Sofya K. Garushyants1,2
  • Harutyun Sahakyan1,2
  • Kira S. Makarova1,7
  • Yuri I. Wolf1,2
  • Simon A. Jackson8,9
  • Franklin L. Nóbrega10,6
  • Chase L. Beisel11,12
  • Eugene V. Koonin13,2
13 affiliations
  1. 1Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA
  2. 2National Institutes of Health
  3. 3Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), 97080 Würzburg, Germany
  4. 4Helmholtz Centre for Infection Research
  5. 5School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK
  6. 6University of Southampton
  7. 7National Institute of Health
  8. 8School of Pharmacy and Biomedical Sciences, Division of Health, University of Waikato, Hamilton 3126, New Zealand. Electronic address: [email protected]
  9. 9University of Waikato
  10. 10School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK. Electronic address: [email protected]
  11. 11Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), 97080 Würzburg, Germany; Medical Faculty, University of Würzburg, 97080 Würzburg, Germany. Electronic address: [email protected]
  12. 12Helmholtz Institute for RNA-based Infection Research
  13. 13Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. Electronic address: [email protected]
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Abstract

Bacteria and archaea possess an enormous variety of antivirus immune systems that often share homologous proteins and domains, some of which contribute to diverse defense strategies. YprA family helicases are central to widespread defense systems DISARM, Dpd, and Druantia. Here, through comprehensive phylogenetic and structural prediction analysis of the YprA family, we identify several major, previously unrecognized clades, with unique signatures of domain architecture and associations with other genes. Each YprA family clade defines a distinct class of defense systems, which we denote ARMADA (disARM-related Antiviral Defense Array), BRIGADE (Base hypermodification and Restriction Involving Genes encoding ARMADA-like and Dpd-like Effectors), or TALON (TOTE-like and ARMADA-Like Operon with Nuclease). In addition to the YprA-like helicase, ARMADA systems share two more proteins with DISARM. However, ARMADA YprA homologs are most similar to those of Druantia, suggesting ARMADA is a 'missing link' connecting DISARM and Druantia. We show experimentally that ARMADA protects bacteria against a broad range of phages via a direct, non-abortive mechanism. We also discovered multiple families of satellite phage-like mobile genetic elements that often carry both ARMADA and Druantia Type III systems and show that these can provide synergistic resistance against diverse phages.

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Cite

BibTeXRIS
BibTeX
@article{bell2026yprafamily,
  title = {{YprA-family helicases provide the missing link between diverse prokaryotic immune systems}},
  author = {Ryan T. Bell and Thomas Gaudin and Yi Wu and Sofya K. Garushyants and Harutyun Sahakyan and Kira S. Makarova and Yuri I. Wolf and Simon A. Jackson and Franklin L. Nóbrega and Chase L. Beisel and Eugene V. Koonin},
  journal = {Cell Host \& Microbe},
  year = {2026},
  month = jun,
  doi = {10.1016/j.chom.2026.05.015},
  url = {https://doi.org/10.1016/j.chom.2026.05.015},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - YprA-family helicases provide the missing link between diverse prokaryotic immune systems
AU  - Ryan T. Bell
AU  - Thomas Gaudin
AU  - Yi Wu
AU  - Sofya K. Garushyants
AU  - Harutyun Sahakyan
AU  - Kira S. Makarova
AU  - Yuri I. Wolf
AU  - Simon A. Jackson
AU  - Franklin L. Nóbrega
AU  - Chase L. Beisel
AU  - Eugene V. Koonin
PY  - 2026
DA  - 2026/06/11
JO  - Cell Host & Microbe
DO  - 10.1016/j.chom.2026.05.015
UR  - https://doi.org/10.1016/j.chom.2026.05.015
AB  - Bacteria and archaea possess an enormous variety of antivirus immune systems that often share homologous proteins and domains, some of which contribute to diverse defense strategies. YprA family helicases are central to widespread defense systems DISARM, Dpd, and Druantia. Here, through comprehensive phylogenetic and structural prediction analysis of the YprA family, we identify several major, previously unrecognized clades, with unique signatures of domain architecture and associations with other genes. Each YprA family clade defines a distinct class of defense systems, which we denote ARMADA (disARM-related Antiviral Defense Array), BRIGADE (Base hypermodification and Restriction Involving Genes encoding ARMADA-like and Dpd-like Effectors), or TALON (TOTE-like and ARMADA-Like Operon with Nuclease). In addition to the YprA-like helicase, ARMADA systems share two more proteins with DISARM. However, ARMADA YprA homologs are most similar to those of Druantia, suggesting ARMADA is a 'missing link' connecting DISARM and Druantia. We show experimentally that ARMADA protects bacteria against a broad range of phages via a direct, non-abortive mechanism. We also discovered multiple families of satellite phage-like mobile genetic elements that often carry both ARMADA and Druantia Type III systems and show that these can provide synergistic resistance against diverse phages.
SN  - 1931-3128
SN  - 1934-6069
ER  -