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Bacterial cGAS senses a viral RNA to initiate immunity

Dalton V Banh1,2, Cameron G Roberts1, Adrian Morales-Amador3

  • 1Laboratory of Bacteriology, The Rockefeller University, New York, NY, USA.

Nature
|November 15, 2023
PubMed

Insights

Cyclic oligonucleotide-based antiphage signalling systems (CBASS) use a phage-encoded RNA (cabRNA) to activate bacterial defenses. Escaping phages evolve cabRNA variants that evade this immune response.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Immunology

Background:

  • Cyclic oligonucleotide-based antiphage signalling systems (CBASS) are prokaryotic defense mechanisms against phage infection.
  • The precise mechanism by which bacterial cyclases detect phage infection remains unclear.

Purpose of the Study:

  • To elucidate how bacterial cyclases recognize phage infection.
  • To identify the molecular components involved in CBASS activation.

Main Methods:

  • Identification and characterization of a phage-derived RNA molecule (cabRNA).
  • Biochemical assays to assess the interaction between cabRNA and the CdnE03 cyclase.
  • Analysis of phage escape mutants and their corresponding cabRNA variants.

Main Results:

  • Staphylococcal phages produce CBASS-activating bacteriophage RNA (cabRNA) from terminase subunit genes.
  • cabRNA binds to the CdnE03 cyclase, promoting cGAMP synthesis and CBASS activation.
  • Phage escape mutants possess altered cabRNA forms that fail to activate CdnE03.

Conclusions:

  • cabRNA is a key phage-derived signal that activates bacterial CBASS immunity.
  • A conserved mechanism exists for activating innate antiviral defenses, involving RNA binding to cyclases, as seen in both prokaryotic CBASS and mammalian interferon responses.

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