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Mechanism of phage sensing and restriction by toxin-antitoxin-chaperone systems

Lookup NU author(s): Dr Jess Buttress, Professor Henrik Strahl von SchultenORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2024 The Author(s). Toxin-antitoxins (TAs) are prokaryotic two-gene systems composed of a toxin neutralized by an antitoxin. Toxin-antitoxin-chaperone (TAC) systems additionally include a SecB-like chaperone that stabilizes the antitoxin by recognizing its chaperone addiction (ChAD) element. TACs mediate antiphage defense, but the mechanisms of viral sensing and restriction are unexplored. We identify two Escherichia coli antiphage TAC systems containing host inhibition of growth (HigBA) and CmdTA TA modules, HigBAC and CmdTAC. HigBAC is triggered through recognition of the gpV major tail protein of phage λ. Chaperone HigC recognizes gpV and ChAD via analogous aromatic molecular patterns, with gpV outcompeting ChAD to trigger toxicity. For CmdTAC, the CmdT ADP-ribosyltransferase toxin modifies mRNA to halt protein synthesis and limit phage propagation. Finally, we establish the modularity of TACs by creating a hybrid broad-spectrum antiphage system combining the CmdTA TA warhead with a HigC chaperone phage sensor. Collectively, these findings reveal the potential of TAC systems in broad-spectrum antiphage defense.


Publication metadata

Author(s): Mets T, Kurata T, Ernits K, Johansson MJO, Craig SZ, Evora GM, Buttress JA, Odai R, Coppieters't Wallant K, Nakamoto JA, Shyrokova L, Egorov AA, Doering CR, Brodiazhenko T, Laub MT, Tenson T, Strahl H, Martens C, Harms A, Garcia-Pino A, Atkinson GC, Hauryliuk V

Publication type: Article

Publication status: Published

Journal: Cell Host and Microbe

Year: 2024

Pages: ePub ahead of Print

Online publication date: 30/05/2024

Acceptance date: 07/05/2024

Date deposited: 25/06/2024

ISSN (print): 1931-3128

ISSN (electronic): 1934-6069

Publisher: Cell Press

URL: https://doi.org/10.1016/j.chom.2024.05.003

DOI: 10.1016/j.chom.2024.05.003

PubMed id: 38821063


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Funding

Funder referenceFunder name
BB/T017570/1
BB/X003035/1
BBSRC

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