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

Picton, David ML, Luyten, Yvette A, Morgan, Richard D, Nelson, Andrew, Smith, Darren L, Dryden, David TF, Hinton, Jay CD ORCID: 0000-0003-2671-6026 and Blower, Tim R (2021) The phage defence island of a multidrug resistant plasmid uses both BREX and type IV restriction for complementary protection from viruses. NUCLEIC ACIDS RESEARCH, 49 (19). pp. 11257-11273.

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Official URL: http://dx.doi.org/10.1093/nar/gkab906

Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	Escherichia, Escherichia coli, Coliphages, DNA Restriction-Modification Enzymes, Bacterial Proteins, Recombinant Proteins, DNA, Viral, Adenosine Triphosphate, Crystallography, X-Ray, Cloning, Molecular, Genomics, Gene Expression, Binding Sites, Genomic Islands, Protein Binding, Substrate Specificity, Plasmids, Models, Molecular, Protein Interaction Domains and Motifs, Protein Multimerization, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	31 Jan 2022 16:49
Last Modified:	18 Jan 2023 21:14
DOI:	10.1093/nar/gkab906
Open Access URL:	https://academic.oup.com/nar/article/49/19/11257/6...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3147892