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

Picton, D.M.; Harling-Lee, J.D.; Duffner, S.J.; Went, S.C.; Morgan, R.D.; Hinton, J.C.D.; Blower, T.R.

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


Authors

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David Picton david.m.picton@durham.ac.uk
PGR Student Doctor of Philosophy

J.D. Harling-Lee

S.J. Duffner

S.C. Went

R.D. Morgan

J.C.D. Hinton



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 characterise 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 homologues are widespread amongst bacteria. About half (48%) of identified BrxR homologues were co-localised 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.

Citation

Picton, D., Harling-Lee, J., Duffner, S., Went, S., Morgan, R., Hinton, J., & Blower, T. (2022). A widespread family of WYL-domain transcriptional regulators co-localises with diverse phage defence systems and islands. Nucleic Acids Research, 50(9), 5191-5207. https://doi.org/10.1093/nar/gkac334

Journal Article Type Article
Acceptance Date Apr 13, 2022
Online Publication Date May 11, 2022
Publication Date May 20, 2022
Deposit Date Apr 20, 2022
Publicly Available Date Apr 20, 2022
Journal Nucleic Acids Research
Print ISSN 0305-1048
Electronic ISSN 1362-4962
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 50
Issue 9
Pages 5191-5207
DOI https://doi.org/10.1093/nar/gkac334

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Copyright Statement
C The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which
permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.






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