2. Academic Validation
  3. DNA glycosylases provide antiviral defence in prokaryotes

DNA glycosylases provide antiviral defence in prokaryotes

  • Nature. 2024 May;629(8011):410-416. doi: 10.1038/s41586-024-07329-9.
Amer A Hossain 1,  Ying Z Pigli 2,  Christian F Baca 1,  Søren Heissel 3,  Alexis Thomas 2,  Vincent K Libis 4,  Ján Burian 4,  Joshua S Chappie 5,  Sean F Brady 4,  Phoebe A Rice 6,  Luciano A Marraffini 7 8
Affiliations

Affiliations

  • 1 Laboratory of Bacteriology, The Rockefeller University, New York, NY, USA.
  • 2 Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA.
  • 3 Proteomics Resource Center, The Rockefeller University, New York, NY, USA.
  • 4 Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, NY, USA.
  • 5 Department of Molecular Medicine, Cornell University, Ithaca, NY, USA.
  • 6 Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA. price@uchicago.edu.
  • 7 Laboratory of Bacteriology, The Rockefeller University, New York, NY, USA. marraffini@rockefeller.edu.
  • 8 Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA. marraffini@rockefeller.edu.
PMID: 38632404 DOI: 10.1038/s41586-024-07329-9
Abstract

Bacteria have adapted to phage predation by evolving a vast assortment of defence systems1. Although anti-phage immunity genes can be identified using bioinformatic tools, the discovery of novel systems is restricted to the available prokaryotic sequence data2. Here, to overcome this limitation, we infected Escherichia coli carrying a soil metagenomic DNA library3 with the lytic coliphage T4 to isolate clones carrying protective genes. Following this approach, we identified Brig1, a DNA glycosylase that excises α-glucosyl-hydroxymethylcytosine nucleobases from the bacteriophage T4 genome to generate abasic sites and inhibit viral replication. Brig1 homologues that provide immunity against T-even phages are present in multiple phage defence loci across distinct clades of bacteria. Our study highlights the benefits of screening unsequenced DNA and reveals prokaryotic DNA glycosylases as important players in the bacteria-phage arms race.

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