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

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 defe...

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Bibliographic Details
Published in:	Cell host & microbe Vol. 32; no. 7; p. 1059
Main Authors:	Mets, Toomas, Kurata, Tatsuaki, Ernits, Karin, Johansson, Marcus J O, Craig, Sophie Z, Evora, Gabriel Medina, Buttress, Jessica A, Odai, Roni, Wallant, Kyo Coppieters't, Nakamoto, Jose A, Shyrokova, Lena, Egorov, Artyom A, Doering, Christopher Ross, Brodiazhenko, Tetiana, Laub, Michael T, Tenson, Tanel, Strahl, Henrik, Martens, Chloe, Harms, Alexander, Garcia-Pino, Abel, Atkinson, Gemma C, Hauryliuk, Vasili
Format:	Journal Article
Language:	English
Published:	United States 10-07-2024
Subjects:	Antitoxins - genetics Antitoxins - metabolism Bacterial Toxins - genetics Bacterial Toxins - metabolism Bacteriophage lambda - genetics Bacteriophage lambda - metabolism Bacteriophage lambda - physiology Bacteriophages - genetics Bacteriophages - metabolism Bacteriophages - physiology Escherichia coli - genetics Escherichia coli - metabolism Escherichia coli - virology Escherichia coli Proteins - genetics Escherichia coli Proteins - metabolism Molecular Chaperones - genetics Molecular Chaperones - metabolism Toxin-Antitoxin Systems - genetics Viral Tail Proteins - genetics Viral Tail Proteins - metabolism ADP-ribosyltransferase phage defense chaperone intrinsically disordered proteins toxin-antitoxin
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Summary:	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.
ISSN:	1934-6069
DOI:	10.1016/j.chom.2024.05.003