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

Publisher: Cell Press Country of Publication: United States NLM ID: 101302316 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1934-6069 (Electronic) Linking ISSN: 19313128 NLM ISO Abbreviation: Cell Host Microbe Subsets: MEDLINE

Original Publication: Cambridge, Mass. : Cell Press

Toxin-Antitoxin Systems*/genetics ; Molecular Chaperones*/metabolism ; Molecular Chaperones*/genetics ; Escherichia coli*/virology ; Escherichia coli*/genetics ; Escherichia coli*/metabolism ; Escherichia coli Proteins*/metabolism ; Escherichia coli Proteins*/genetics; Bacteriophage lambda/genetics ; Bacteriophage lambda/physiology ; Bacteriophage lambda/metabolism ; Bacterial Toxins/metabolism ; Bacterial Toxins/genetics ; Bacteriophages/genetics ; Bacteriophages/metabolism ; Bacteriophages/physiology ; Antitoxins/metabolism ; Antitoxins/genetics ; Viral Tail Proteins/metabolism ; Viral Tail Proteins/genetics

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.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Keywords: ADP-ribosyltransferase; chaperone; intrinsically disordered proteins; phage defense; toxin-antitoxin

0 (Molecular Chaperones)
0 (Escherichia coli Proteins)
0 (Bacterial Toxins)
0 (Antitoxins)
0 (Viral Tail Proteins)

Date Created: 20240531 Date Completed: 20240711 Latest Revision: 20240712

20240713

10.1016/j.chom.2024.05.003

38821063