The phage defence island of a multidrug resistant plasmid uses both BREX and type IV restriction for complementary protection from viruses.

Autor: Picton DM; Department of Biosciences, Durham University, Stockton Road, Durham DH1 3LE, UK., Luyten YA; New England Biolabs, 240 County Road, Ipswich, MA 01938, USA., Morgan RD; New England Biolabs, 240 County Road, Ipswich, MA 01938, USA., Nelson A; Department of Applied Sciences, University of Northumbria, Newcastle Upon Tyne NE1 8ST, UK., Smith DL; Department of Applied Sciences, University of Northumbria, Newcastle Upon Tyne NE1 8ST, UK., Dryden DTF; Department of Biosciences, Durham University, Stockton Road, Durham DH1 3LE, UK., Hinton JCD; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7ZB, UK., Blower TR; Department of Biosciences, Durham University, Stockton Road, Durham DH1 3LE, UK.
Jazyk: angličtina
Zdroj: Nucleic acids research [Nucleic Acids Res] 2021 Nov 08; Vol. 49 (19), pp. 11257-11273.
DOI: 10.1093/nar/gkab906
Abstrakt: Bacteria have evolved a multitude of systems to prevent invasion by bacteriophages and other mobile genetic elements. Comparative genomics suggests that genes encoding bacterial defence mechanisms are often clustered in 'defence islands', providing a concerted level of protection against a wider range of attackers. However, there is a comparative paucity of information on functional interplay between multiple defence systems. Here, we have functionally characterised a defence island from a multidrug resistant plasmid of the emerging pathogen Escherichia fergusonii. Using a suite of thirty environmentally-isolated coliphages, we demonstrate multi-layered and robust phage protection provided by a plasmid-encoded defence island that expresses both a type I BREX system and the novel GmrSD-family type IV DNA modification-dependent restriction enzyme, BrxU. We present the structure of BrxU to 2.12 Å, the first structure of the GmrSD family of enzymes, and show that BrxU can utilise all common nucleotides and a wide selection of metals to cleave a range of modified DNAs. Additionally, BrxU undergoes a multi-step reaction cycle instigated by an unexpected ATP-dependent shift from an intertwined dimer to monomers. This direct evidence that bacterial defence islands can mediate complementary layers of phage protection enhances our understanding of the ever-expanding nature of phage-bacterial interactions.
(© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze: MEDLINE