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Serine Recombinase PinR Inverts Cryptic Prophage DNA to Block Adsorption of Phages
Open accessPreprint — published as 10.1093/nar/gkaf1041
Abstract
Recombinases catalyze site-specific integration, excision, and inversion of DNA and are found in myriad defense islands; however, their function in phage-defense is unknown as they are frequently dismissed as markers of prophages. Here, we characterize the physiological role of the previously-uncharacterized serine recombinase PinR of Escherichia coli cryptic prophage rac and discover that it inhibits T2 phage infection by inverting a 1,797 bp segment in a different cryptic prophage e14 to inhibit T2 infection; this inversion leads to the formation of a novel protein from two spliced genes, StfE2, that we find blocks phage adsorption. Modeling shows StfE2 inhibits T2 phage adsorption by preventing Gp38 binding to its primary receptors porins FadL and OmpF. Corroborating the receptor-blocking hypothesis, T2 escape mutants evolve resistance to PinR phage defense by mutating gp38 to remove 16 aa in the hyper variable region 3. Therefore, we discovered the first recombinase-activated phage inhibition system.
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Varadi, M., Bertoni, D., Magana, P., Paramval, U., Pidruchna, I., Radhakrishnan, M., Tsenkov, M., Nair, S., Mirdita, M., Yeo, J., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkad1011 · Cited by 2,052 · cited 2×
“Exploring structural insights using AlphaFold (39), we found PinR has all the structural features of a small serine recombinase (40), including a DNA binding site, arm region, and catalytic domain ( Fig.”
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Metadata
- Authors
- Kirigo, J., Huelgas-Méndez, D., Benedik, M. J., García-Contreras, R., & Wood, T. K.
- Affiliations
- Pennsylvania State University (US)
- Department of Microbiology and Parasitology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
- Texas A&M University (US)
- Corresponding author
- Wood, Thomas K.
- Venue
- Nucleic Acids Research
- Publisher
- openRxiv
- Published
- 2025-03-28
- Volume
- 53
- Issue
- 19
- ISSN
- 0305-1048 (ISSN-L)
- PMC
- PMC12529663
- OpenAlex
- W4415263929
- Cited by
- 1
- References
- 1
- Citations by year
- 2026: 1
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
- Funders
- Pennsylvania State University
- Universidad Nacional Autónoma de México (IN200224)
- Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- serine recombinase, DNA inversion, anti-phage defense, Escherichia coli
- MeSH terms
- DNA, Viral, Escherichia coli, T-Phages, Viral Proteins, Porins, Escherichia coli Proteins, Prophages, Recombinases
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