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Cited by 8Bacteriophages and microbial interactionsBacterial Genetics and BiotechnologyInvertebrate Immune Response Mechanisms

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A phage protein screen identifies triggers of the bacterial innate immune system

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Nagy, Toni A., Gersabeck, Gina W., Conte, Amy N., Whiteley, Aaron T.·2026·Nature Microbiology
DOI 10.1038/s41564-025-02239-6PMC PMC12875140

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Abstract

Bacteria have evolved sophisticated antiphage systems that halt phage replication upon detecting specific phage triggers. Identifying phage triggers is crucial to our understanding of immune signalling; however, they are challenging to predict. Here we used a plasmid library that expressed over 400 phage protein-coding genes from 6 phages to identify triggers of known and undiscovered antiphage systems. We transformed our library into 39 diverse strains of E. coli. Each strain natively harbours a different suite of antiphage systems whose activation typically inhibits growth. By tracking plasmids that were selectively depleted, we identified over 100 candidate phage trigger-E. coli pairs. Two phage proteins were further investigated, revealing that T7 gp17 and additional tail fibre proteins activated the undescribed antiphage system PD-T2-1 and identifying that λ gpE major capsid protein activated the antiphage system Avs8. These experiments provide a unique dataset for the continued definition of the molecular mechanisms underlying the bacterial immune system.

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Metadata

Authors
Nagy, T. A., Gersabeck, G. W., Conte, A. N., & Whiteley, A. T.
Affiliations
University of Colorado Boulder (US)
Corresponding author
Whiteley, Aaron T.
ORCID
Venue
Nature Microbiology
Publisher
Springer Science and Business Media LLC
Published
2026-01-16
Volume
11
Issue
2
Pages
597-609
ISSN
2058-5276 (ISSN-L)
DOI
10.1038/s41564-025-02239-6
PMC
PMC12875140
OpenAlex
W7124455424
Cited by
8
References
4
Citations by year
2026: 8
FWCI
27.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Microbiology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • U.S. Department of Health & Human Services | NIH | NIH Office of the Director (DP2AT012346)
  • Pew Charitable Trusts (36883)
  • Burroughs Wellcome Fund (1186087)
  • Boettcher Foundation (NA)
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 › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
Keywords
bacterial innate immunity, Escherichia coli, bacteriophage T7, bacteriophage lambda, major capsid protein, immune signaling, plasmid library

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