Direct activation of a bacterial innate immune system by a viral capsid protein
Name
s41586-022-05444-z.pdf
Description
Published version
Size
30.95 MB
Format
Adobe PDF
Checksum (MD5)
141ae8d36eab6a0727ea0be32fd0edb0
Author(s)
Zhang, Tong
Tamman, Hedvig
Coppieters ’t Wallant, Kyo
Kurata, Tatsuaki
LeRoux, Michele
Srikant, Sriram
Brodiazhenko, Tetiana
Cepauskas, Albinas
Talavera, Ariel
Martens, Chloe
Date Issued
December 1, 2022
Journal
Nature
Publisher
Springer Science and Business Media LLC
Citation
Zhang, Tong, Tamman, Hedvig, Coppieters ’t Wallant, Kyo, Kurata, Tatsuaki, LeRoux, Michele et al. 2022. "Direct activation of a bacterial innate immune system by a viral capsid protein." Nature, 612 (7938).
Version
Final published version
Abstract
AbstractBacteria have evolved diverse immunity mechanisms to protect themselves against the constant onslaught of bacteriophages1–3. Similar to how eukaryotic innate immune systems sense foreign invaders through pathogen-associated molecular patterns4 (PAMPs), many bacterial immune systems that respond to bacteriophage infection require phage-specific triggers to be activated. However, the identities of such triggers and the sensing mechanisms remain largely unknown. Here we identify and investigate the anti-phage function of CapRelSJ46, a fused toxin–antitoxin system that protects Escherichia coli against diverse phages. Using genetic, biochemical and structural analyses, we demonstrate that the C-terminal domain of CapRelSJ46 regulates the toxic N-terminal region, serving as both antitoxin and phage infection sensor. Following infection by certain phages, newly synthesized major capsid protein binds directly to the C-terminal domain of CapRelSJ46 to relieve autoinhibition, enabling the toxin domain to pyrophosphorylate tRNAs, which blocks translation to restrict viral infection. Collectively, our results reveal the molecular mechanism by which a bacterial immune system directly senses a conserved, essential component of phages, suggesting a PAMP-like sensing model for toxin–antitoxin-mediated innate immunity in bacteria. We provide evidence that CapRels and their phage-encoded triggers are engaged in a ‘Red Queen conflict’5, revealing a new front in the intense coevolutionary battle between phages and bacteria. Given that capsid proteins of some eukaryotic viruses are known to stimulate innate immune signalling in mammalian hosts6–10, our results reveal a deeply conserved facet of immunity.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/s41586-022-05444-z
