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Publication Abstract from PubMed

Bacteria have evolved diverse immunity mechanisms to protect themselves against the constant onslaught of bacteriophages(1-3). Similar to how eukaryotic innate immune systems sense foreign invaders through pathogen-associated molecular patterns(4) (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 CapRel(SJ46), 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 CapRel(SJ46) 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 CapRel(SJ46) 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 hosts(6-10), our results reveal a deeply conserved facet of immunity.

Direct activation of a bacterial innate immune system by a viral capsid protein.,Zhang T, Tamman H, Coppieters 't Wallant K, Kurata T, LeRoux M, Srikant S, Brodiazhenko T, Cepauskas A, Talavera A, Martens C, Atkinson GC, Hauryliuk V, Garcia-Pino A, Laub MT Nature. 2022 Dec;612(7938):132-140. doi: 10.1038/s41586-022-05444-z. Epub 2022 , Nov 16. PMID:36385533^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.