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

Mets, Toomas LU ; Kurata, Tatsuaki LU ; Ernits, Karin LU ; Johansson, Marcus J O LU ; Craig, Sophie Z ; Evora, Gabriel Medina ; Buttress, Jessica A ; Odai, Roni LU ; Wallant, Kyo Coppieters't and Nakamoto, Jose A LU orcid , et al. (2024) In Cell Host and Microbe
Abstract

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... (More)

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.

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type
Contribution to journal
publication status
epub
subject
in
Cell Host and Microbe
publisher
Elsevier
external identifiers
  • pmid:38821063
ISSN
1934-6069
DOI
10.1016/j.chom.2024.05.003
language
English
LU publication?
yes
additional info
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
id
90498675-3e13-470e-8378-993b712ebe62
date added to LUP
2024-06-09 11:19:05
date last changed
2024-06-10 09:12:33
@article{90498675-3e13-470e-8378-993b712ebe62,
  abstract     = {{<p>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.</p>}},
  author       = {{Mets, Toomas and Kurata, Tatsuaki and Ernits, Karin and Johansson, Marcus J O and Craig, Sophie Z and Evora, Gabriel Medina and Buttress, Jessica A and Odai, Roni and Wallant, Kyo Coppieters't and Nakamoto, Jose A and Shyrokova, Lena and Egorov, Artyom A and Doering, Christopher Ross and Brodiazhenko, Tetiana and Laub, Michael T and Tenson, Tanel and Strahl, Henrik and Martens, Chloe and Harms, Alexander and Garcia-Pino, Abel and Atkinson, Gemma C and Hauryliuk, Vasili}},
  issn         = {{1934-6069}},
  language     = {{eng}},
  month        = {{05}},
  publisher    = {{Elsevier}},
  series       = {{Cell Host and Microbe}},
  title        = {{Mechanism of phage sensing and restriction by toxin-antitoxin-chaperone systems}},
  url          = {{http://dx.doi.org/10.1016/j.chom.2024.05.003}},
  doi          = {{10.1016/j.chom.2024.05.003}},
  year         = {{2024}},
}