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

Toomas Mets1, Tatsuaki Kurata2, Karin Ernits2

  • 1Department of Experimental Medical Science, Lund University, 221 00 Lund, Sweden; University of Tartu, Institute of Technology, 50411 Tartu, Estonia.

Cell Host & Microbe
|May 31, 2024
PubMed

Insights

Prokaryotic toxin-antitoxin-chaperone (TAC) systems defend against phages. Researchers uncovered how two Escherichia coli TAC systems, HigBAC and CmdTAC, recognize and neutralize viral threats, revealing potential for broad-spectrum phage defense.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Bacteriology

Background:

  • Toxin-antitoxin (TA) systems are prokaryotic genetic elements.
  • Toxin-antitoxin-chaperone (TAC) systems include a chaperone that stabilizes the antitoxin.
  • The mechanisms of TAC-mediated antiphage defense are largely unknown.

Purpose of the Study:

  • To investigate the mechanisms of two Escherichia coli antiphage TAC systems: HigBAC and CmdTAC.
  • To explore how these TAC systems sense and restrict phage infection.
  • To assess the potential for engineering novel phage defense strategies using TAC systems.

Main Methods:

  • Identification and characterization of HigBAC and CmdTAC antiphage systems in E. coli.
  • Analysis of the interaction between the HigC chaperone, phage λ gpV protein, and the ChAD element.
  • Investigation of the CmdT toxin's mechanism of inhibiting protein synthesis.
  • Construction and testing of a hybrid TAC system.

Main Results:

  • HigBAC is activated by the phage λ gpV protein, which outcompetes the ChAD element for binding to the HigC chaperone.
  • CmdTAC utilizes the CmdT toxin, an ADP-ribosyltransferase, to modify mRNA and inhibit phage protein synthesis.
  • A hybrid TAC system was successfully created, demonstrating modularity and broad-spectrum potential.

Conclusions:

  • TAC systems employ distinct mechanisms for phage sensing and restriction.
  • The HigBAC system uses molecular mimicry for phage detection.
  • The CmdTAC system directly interferes with phage protein synthesis.
  • TAC systems offer a versatile platform for developing novel antiphage strategies.
Keywords:
ADP-ribosyltransferasechaperoneintrinsically disordered proteinsphage defensetoxin-antitoxin

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