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Nuclease-NTPase antiphage defence systems use conserved molecular features to control bacterial immunity

Ragucci, Adelyn E ; Antine, Sadie P ; Leviss, Ethan M ; Mooney, Sarah E ; Garcia, Jasmine M ; Shyrokova, Lena LU orcid ; Hauryliuk, Vasili LU orcid ; Lee, Amy S Y and Kranzusch, Philip J (2026) In Nature Microbiology
Abstract

Bacteria encode diverse defence systems, including restriction-modification and CRISPR-Cas, that cleave nucleic acid to protect against phage infection. Bioinformatic analyses demonstrate that many recently identified antiphage defence operons comprise a nuclease and NTPase protein, suggesting that additional nucleic acid-targeting systems remain to be understood. Here we develop large-scale comparative cell biology and biochemical approaches to analyse 16 nuclease-NTPase systems and define molecular features that control antiphage defence. Purification, biochemical characterization and in vitro reconstitution of nucleic acid degradation demonstrates that protein-protein complex formation is a shared feature of multigene nuclease-NTPase... (More)

Bacteria encode diverse defence systems, including restriction-modification and CRISPR-Cas, that cleave nucleic acid to protect against phage infection. Bioinformatic analyses demonstrate that many recently identified antiphage defence operons comprise a nuclease and NTPase protein, suggesting that additional nucleic acid-targeting systems remain to be understood. Here we develop large-scale comparative cell biology and biochemical approaches to analyse 16 nuclease-NTPase systems and define molecular features that control antiphage defence. Purification, biochemical characterization and in vitro reconstitution of nucleic acid degradation demonstrates that protein-protein complex formation is a shared feature of multigene nuclease-NTPase systems. We show that PaAbpAB, BtHachiman and EcPD-T4-8 system nucleases use highly degenerate recognition site preferences to enable broad nucleic acid degradation, and the Azaca system exhibits specific phage targeting through the recognition of modified phage genomic DNA. Our results uncover principles of antiphage defence system function and highlight the mechanistic diversity of nuclease-NTPase systems in bacterial immunity.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Nature Microbiology
publisher
Springer Nature
external identifiers
  • scopus:105037530497
  • pmid:42045369
ISSN
2058-5276
DOI
10.1038/s41564-026-02312-8
project
Experimental exploration of bacterial toxin-antitoxin systems
För banbrytande studier av hur proteinsyntes regleras i bakterier
language
English
LU publication?
yes
additional info
© 2026. The Author(s), under exclusive licence to Springer Nature Limited.
id
a518e358-1ba9-4bbe-a41a-3e2c6c15c5bc
date added to LUP
2026-04-28 07:04:11
date last changed
2026-07-22 15:46:46
@article{a518e358-1ba9-4bbe-a41a-3e2c6c15c5bc,
  abstract     = {{<p>Bacteria encode diverse defence systems, including restriction-modification and CRISPR-Cas, that cleave nucleic acid to protect against phage infection. Bioinformatic analyses demonstrate that many recently identified antiphage defence operons comprise a nuclease and NTPase protein, suggesting that additional nucleic acid-targeting systems remain to be understood. Here we develop large-scale comparative cell biology and biochemical approaches to analyse 16 nuclease-NTPase systems and define molecular features that control antiphage defence. Purification, biochemical characterization and in vitro reconstitution of nucleic acid degradation demonstrates that protein-protein complex formation is a shared feature of multigene nuclease-NTPase systems. We show that PaAbpAB, BtHachiman and EcPD-T4-8 system nucleases use highly degenerate recognition site preferences to enable broad nucleic acid degradation, and the Azaca system exhibits specific phage targeting through the recognition of modified phage genomic DNA. Our results uncover principles of antiphage defence system function and highlight the mechanistic diversity of nuclease-NTPase systems in bacterial immunity.</p>}},
  author       = {{Ragucci, Adelyn E and Antine, Sadie P and Leviss, Ethan M and Mooney, Sarah E and Garcia, Jasmine M and Shyrokova, Lena and Hauryliuk, Vasili and Lee, Amy S Y and Kranzusch, Philip J}},
  issn         = {{2058-5276}},
  language     = {{eng}},
  month        = {{04}},
  publisher    = {{Springer Nature}},
  series       = {{Nature Microbiology}},
  title        = {{Nuclease-NTPase antiphage defence systems use conserved molecular features to control bacterial immunity}},
  url          = {{http://dx.doi.org/10.1038/s41564-026-02312-8}},
  doi          = {{10.1038/s41564-026-02312-8}},
  year         = {{2026}},
}