DNA glycosylases provide antiviral defence in prokaryotes

• 成果类型: Article
• 署名作者: Hossain, Amer A.; Pigli, Ying Z.; Baca, Christian F.; Heissel, Soren; Thomas, Alexis; Libis, Vincent K.; Burian, Jan; Chappie, Joshua S.; Brady, Sean F.; Rice, Phoebe A.; Marraffini, Luciano A.
• 署名单位: Rockefeller University; University of Chicago; Rockefeller University; Rockefeller University; Cornell University; Rockefeller University; Howard Hughes Medical Institute
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6501
• DOI: 10.1038/s41586-024-07329-9
• 发表日期: 2024-05-09
• 页码: 410-+
• 关键词: escherichia-coli; nucleotide-sequence; immune-systems; bacteria; reveals; FAMILY; repair; glucosyltransferase; identification; gene

摘要

Bacteria have adapted to phage predation by evolving a vast assortment of defence systems(1). Although anti-phage immunity genes can be identified using bioinformatic tools, the discovery of novel systems is restricted to the available prokaryotic sequence data(2). Here, to overcome this limitation, we infected Escherichia coli carrying a soil metagenomic DNA library(3) with the lytic coliphage T4 to isolate clones carrying protective genes. Following this approach, we identified Brig1, a DNA glycosylase that excises alpha-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.