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bioRxiv · 10.1101/2021.12.19.473342

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.
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Abstract

AO_SCPLOWBSTRACTC_SCPLOWBacteria 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 [A], 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.

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Picton, D. M., Harling-Lee, J. D., Duffner, S. J., Went, S. C., Morgan, R. D., Hinton, J. C. D., Blower, T. R.. 2021-12-19. A widespread family of WYL-domain transcriptional regulators co-localises with diverse phage defence systems and islands. https://doi.org/10.1101/2021.12.19.473342

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