期刊
NUCLEIC ACIDS RESEARCH
卷 50, 期 9, 页码 5191-5207出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkac334
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资金
- Biotechnology and Biological Sciences Research Council Newcastle-Liverpool-Durham Doctoral Training Partnership studentship [BB/M011186/1]
- Lister Institute Prize Fellowship
- Principal's Career Development Scholarship (University of Edinburgh)
- Engineering and Physical Sciences Research Council Molecular Sciences for Medicine Centre for Doctoral Training studentship [EP/S022791/1]
- Biophysical Sciences Institute at Durham University
- Wellcome Trust Senior Investigator award [106914/Z/15/Z]
- Wellcome Trust [106914/Z/15/Z] Funding Source: Wellcome Trust
This study identifies a novel transcriptional regulator, BrxR, and investigates its repressor role in bacterial phage defense systems. Structural analysis and bioinformatic analysis reveal the widespread presence of BrxR in bacteria and its co-localization with various phage defense systems.
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 angstrom, 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.
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