A widespread family of WYL-domain transcriptional regulators co-localizes with diverse phage defence systems and islands

Picton, David M, Harling-Lee, Joshua D, Duffner, Samuel J, Went, Sam C, Morgan, Richard D, Hinton, Jay CD ORCID: 0000-0003-2671-6026 and Blower, Tim R (2022) A widespread family of WYL-domain transcriptional regulators co-localizes with diverse phage defence systems and islands. NUCLEIC ACIDS RESEARCH, 50 (9). pp. 5191-5207.

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Official URL: http://dx.doi.org/10.1093/nar/gkac334

Abstract

Bacteria are under constant assault by bacteriophages and other mobile genetic elements. As a result, bacteria have evolved a multitude of systems that protect from attack. Genes encoding bacterial defence mechanisms can be clustered into 'defence islands', providing a potentially synergistic level of protection against a wider range of assailants. However, there is a comparative paucity of information on how expression of these defence systems is controlled. Here, we functionally characterize a transcriptional regulator, BrxR, encoded within a recently described phage defence island from a multidrug resistant plasmid of the emerging pathogen Escherichia fergusonii. Using a combination of reporters and electrophoretic mobility shift assays, we discovered that BrxR acts as a repressor. We present the structure of BrxR to 2.15 Å, the first structure of this family of transcription factors, and pinpoint a likely binding site for ligands within the WYL-domain. Bioinformatic analyses demonstrated that BrxR-family homologues are widespread amongst bacteria. About half (48%) of identified BrxR homologues were co-localized with a diverse array of known phage defence systems, either alone or clustered into defence islands. BrxR is a novel regulator that reveals a common mechanism for controlling the expression of the bacterial phage defence arsenal.

Item Type:	Article
Uncontrolled Keywords:	Bacteria, Bacteriophages, Transcription Factors, Genomic Islands, Plasmids
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:	11 Oct 2022 10:27
Last Modified:	18 Jan 2023 20:37
DOI:	10.1093/nar/gkac334
Open Access URL:	https://doi.org/10.1093/nar/gkac334
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3165327