DNA glycosylases provide antiviral defence in prokaryotes

Amer A. Hossain, Ying Z. Pigli, Christian F. Baca, Søren Heissel, Alexis Thomas, Vincent K. Libis, Ján Burian, Joshua S. Chappie, Sean F. Brady, Phoebe A. Rice () and Luciano A. Marraffini ()
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Amer A. Hossain: The Rockefeller University
Ying Z. Pigli: University of Chicago
Christian F. Baca: The Rockefeller University
Søren Heissel: The Rockefeller University
Alexis Thomas: University of Chicago
Vincent K. Libis: The Rockefeller University
Ján Burian: The Rockefeller University
Joshua S. Chappie: Cornell University
Sean F. Brady: The Rockefeller University
Phoebe A. Rice: University of Chicago
Luciano A. Marraffini: The Rockefeller University

Nature, 2024, vol. 629, issue 8011, 410-416

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41586-024-07329-9

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