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Lookup NU author(s): Dr Jess Buttress, Dr Henrik Strahl von SchultenORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 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.
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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