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A large-scale type I CBASS antiphage screen identifies the phage prohead protease as a key determinant of immune activation and evasion.

Desmond Richmond-BuccolaSamuel J HobbsJasmine M GarciaHunter ToyodaJingjing GaoSichen ShaoAmy S Y LeePhilip J Kranzusch
Published in: Cell host & microbe (2024)
Cyclic oligonucleotide-based signaling system (CBASS) is an antiviral system that protects bacteria from phage infection and is evolutionarily related to human cGAS-STING immunity. cGAS-STING signaling is initiated by the recognition of viral DNA, but the molecular cues activating CBASS are incompletely understood. Using a screen of 975 type I CBASS operon-phage challenges, we show that operons with distinct cGAS/DncV-like nucleotidyltransferases (CD-NTases) and CD-NTase-associated protein (Cap) effectors exhibit marked patterns of phage restriction. We find that some type I CD-NTase enzymes require a C-terminal AGS-C immunoglobulin (Ig)-like fold domain for defense against select phages. Escaper phages evade CBASS via protein-coding mutations in virion assembly proteins, and acquired resistance is largely operon specific. We demonstrate that the phage Bas13 prohead protease interacts with the CD-NTase EcCdnD12 and can induce CBASS-dependent growth arrest in cells. Our results define phage virion assembly as a determinant of type I CBASS immune evasion and support viral protein recognition as a putative mechanism of cGAS-like enzyme activation.
Keyphrases
  • pseudomonas aeruginosa
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  • endothelial cells
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  • high throughput
  • gene expression
  • single molecule
  • cell cycle
  • endoplasmic reticulum stress
  • cell free
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  • innate immune