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

Aaron Whiteley — Fri, 16 Jan 2026 16:00:00 +0000

A phage protein screen identifies triggers of the bacterial innate immune system Aaron Whiteley Fri, 01/16/2026 - 09:00

Toni Nagy , Gina Gersabeck , Amy Conte , Aaron Whiteley

Nature Microbiology (2026). PubMed PMID: 41545502

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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Nagy TA, Gersabeck GW, Conte AN, Whiteley AT. A phage protein screen identifies triggers of the bacterial innate immune system. Nat Microbiol. 2026 Jan 16. doi: 10.1038/s41564-025-02239-6. Epub ahead of print. PMID: 41545502.

Nagy TA, Gersabeck GW, Conte AN, ➤Whiteley AT | Nature Microbiology 2026

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

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