DNA Glycosylases Provide Antiviral Defence in Prokaryotes

Overview

Journal Nature

Specialty Science

Date 2024 Apr 17

PMID 38632404

Authors

Amer A Hossain

Ying Z Pigli

Christian F Baca

Soren Heissel

Alexis Thomas

Vincent K Libis

Jan Burian

Joshua S Chappie

Sean F Brady

Phoebe A Rice

Luciano A Marraffini

Affiliations

Soon will be listed here.

Abstract

Bacteria have adapted to phage predation by evolving a vast assortment of defence systems. Although anti-phage immunity genes can be identified using bioinformatic tools, the discovery of novel systems is restricted to the available prokaryotic sequence data. Here, to overcome this limitation, we infected Escherichia coli carrying a soil metagenomic DNA library 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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