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.

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
• Public URL: https://durham-repository.worktribe.com/output/1207885