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Peer-reviewedCC BY 4.0PLOS Biology

Small serine recombinases are markers for antiphage defense system discovery

  • Shelby E. Andersen1
  • Joshua M. Kirsch2
  • Navtej Singh3
  • Stephen R. Garrett4
  • John C. Whitney
  • Jay R. Hesselberth
  • Breck A. Duerkop
4 affiliations
  1. 1Department of Immunology and Microbiology, University of Colorado School – Anschutz Medical Campus, School of Medicine, Aurora, Colorado, United States of America
  2. 2Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
  3. 3Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada
  4. 4Department of Biochemistry and Molecular Genetics, University of Colorado School – Anschutz Medical Campus, School of Medicine, Aurora, Colorado, United States of America
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Abstract

Renewed interest in phage therapy has highlighted a need to understand how bacteria subvert phage infection through antiphage defense systems. Traditionally, strategies to identify antiphage defense systems lack throughput or have limitations for bacterial species where antiphage defense systems are understudied. Herein, we developed a bioinformatic pipeline that uses a small serine recombinase to identify known and unknown antiphage defense systems. Using this approach to query reference genomes and metagenomes, we show that small serine recombinase genes are genetically linked to antiphage defense systems and serve as bait for finding these systems across diverse bacterial phyla. Using co-transcription predictions and statistical analysis of protein domain abundances, we experimentally validated our bioinformatic approach by discovering that KAP P-loop NTPases are fused to putative antiphage domains and reinforce prokaryotic Schlafen proteins as a new class of antiphage defense. Our work shows that small serine recombinases are a reliable genetic marker for the discovery of antiphage defenses across diverse bacterial phyla.

Identifying antiphage defense systems is challenging for bacterial species where such systems are understudied. This study describes a bioinformatic pipeline that uses a small serine recombinase as a genetic marker to identify novel antiphage defense systems across diverse bacterial phyla.

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Cite

BibTeXRIS
BibTeX
@article{andersen2026small,
  title = {{Small serine recombinases are markers for antiphage defense system discovery}},
  author = {Shelby E. Andersen and Joshua M. Kirsch and Navtej Singh and Stephen R. Garrett and John C. Whitney and Jay R. Hesselberth and Breck A. Duerkop},
  journal = {PLOS Biology},
  year = {2026},
  month = aug,
  doi = {10.1371/journal.pbio.3003991},
  url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003991},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Small serine recombinases are markers for antiphage defense system discovery
AU  - Shelby E. Andersen
AU  - Joshua M. Kirsch
AU  - Navtej Singh
AU  - Stephen R. Garrett
AU  - John C. Whitney
AU  - Jay R. Hesselberth
AU  - Breck A. Duerkop
PY  - 2026
DA  - 2026/08/31
JO  - PLOS Biology
DO  - 10.1371/journal.pbio.3003991
UR  - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003991
AB  - Renewed interest in phage therapy has highlighted a need to understand how bacteria subvert phage infection through antiphage defense systems. Traditionally, strategies to identify antiphage defense systems lack throughput or have limitations for bacterial species where antiphage defense systems are understudied. Herein, we developed a bioinformatic pipeline that uses a small serine recombinase to identify known and unknown antiphage defense systems. Using this approach to query reference genomes and metagenomes, we show that small serine recombinase genes are genetically linked to antiphage defense systems and serve as bait for finding these systems across diverse bacterial phyla. Using co-transcription predictions and statistical analysis of protein domain abundances, we experimentally validated our bioinformatic approach by discovering that KAP P-loop NTPases are fused to putative antiphage domains and reinforce prokaryotic Schlafen proteins as a new class of antiphage defense. Our work shows that small serine recombinases are a reliable genetic marker for the discovery of antiphage defenses across diverse bacterial phyla.  Identifying antiphage defense systems is challenging for bacterial species where such systems are understudied. This study describes a bioinformatic pipeline that uses a small serine recombinase as a genetic marker to identify novel antiphage defense systems across diverse bacterial phyla.
SN  - 1545-7885
ER  -