A widespread family of WYL-domain transcriptional regulators co-localizes with diverse phage defence systems and islands.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
20 05 2022
20 05 2022
Historique:
accepted:
21
04
2022
revised:
28
03
2022
received:
20
12
2021
pubmed:
12
5
2022
medline:
25
5
2022
entrez:
11
5
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35544231
pii: 6584439
doi: 10.1093/nar/gkac334
pmc: PMC9122601
doi:
Substances chimiques
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5191-5207Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M011186/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106914/Z/15/Z
Pays : United Kingdom
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
Microb Genom. 2016 Sep 20;2(9):e000086
pubmed: 28785418
Structure. 2019 Jan 2;27(1):6-26
pubmed: 30393050
Cell. 1995 Jan 27;80(2):237-48
pubmed: 7834743
Science. 2018 Mar 2;359(6379):
pubmed: 29371424
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
J Bacteriol. 2009 Oct;191(19):6029-39
pubmed: 19633081
Curr Opin Struct Biol. 2000 Feb;10(1):110-6
pubmed: 10679470
Nat Rev Microbiol. 2010 May;8(5):317-27
pubmed: 20348932
J Bacteriol. 1995 Jul;177(14):4121-30
pubmed: 7608087
Nucleic Acids Res. 2016 Jul 8;44(W1):W344-50
pubmed: 27166375
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42
pubmed: 21460441
Nature. 2020 Jan;577(7790):327-336
pubmed: 31942051
Nat Protoc. 2015 Jun;10(6):845-58
pubmed: 25950237
Biochemistry. 2018 Feb 20;57(7):1108-1118
pubmed: 29341597
Vet Microbiol. 2014 Aug 6;172(1-2):7-12
pubmed: 24861842
Nucleic Acids Res. 2022 May 20;50(9):5239-5250
pubmed: 35536256
Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):894-9
pubmed: 19124776
Bioessays. 2011 Jan;33(1):43-51
pubmed: 20979102
Cell Host Microbe. 2021 Nov 10;29(11):1620-1633.e8
pubmed: 34597593
Nat Commun. 2019 Oct 11;10(1):4653
pubmed: 31604936
Mol Microbiol. 1992 May;6(9):1079-86
pubmed: 1316984
Microbiol Mol Biol Rev. 2000 Mar;64(1):69-114
pubmed: 10704475
Nucleic Acids Res. 2013 Apr;41(8):4360-77
pubmed: 23470997
Mol Biol Evol. 2016 Jun;33(6):1635-8
pubmed: 26921390
Annu Rev Virol. 2020 Sep 29;7(1):371-384
pubmed: 32559405
Mol Cell. 2018 Apr 19;70(2):327-339.e5
pubmed: 29551514
EMBO J. 2002 Jul 1;21(13):3546-56
pubmed: 12093755
J Bacteriol. 2004 Jun;186(12):3677-86
pubmed: 15175280
Nucleic Acids Res. 2022 May 20;50(9):5171-5190
pubmed: 35511079
Virology. 2007 Sep 1;365(2):241-9
pubmed: 17482656
RNA Biol. 2013 May;10(5):852-64
pubmed: 23535141
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
Nucleic Acids Res. 2019 Jan 10;47(1):253-265
pubmed: 30418590
Cell. 2020 Dec 10;183(6):1551-1561.e12
pubmed: 33157039
Nucleic Acids Res. 2019 Jun 4;47(10):5420-5428
pubmed: 30976796
J Bacteriol. 2011 Nov;193(21):6039-56
pubmed: 21908672
Nucleic Acids Res. 2014 Apr;42(7):4590-605
pubmed: 24465005
Mol Biol Evol. 2018 Dec 1;35(12):3041-3043
pubmed: 30351396
J Immunol. 2006 Feb 1;176(3):1295-6
pubmed: 16424152
PLoS One. 2008;3(11):e3647
pubmed: 18985154
Acta Crystallogr D Biol Crystallogr. 2006 Sep;62(Pt 9):1002-11
pubmed: 16929101
EMBO J. 2015 Jan 13;34(2):169-83
pubmed: 25452498
Nat Rev Microbiol. 2020 Feb;18(2):67-83
pubmed: 31857715
FEMS Microbiol Lett. 1992 Aug 15;74(2-3):271-6
pubmed: 1526459
Nature. 2021 Jan;589(7840):120-124
pubmed: 32937646
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Front Genet. 2014 Apr 30;5:102
pubmed: 24817877
Nucleic Acids Res. 2014 Jan;42(1):45-55
pubmed: 23863841
Mol Cell. 2020 Feb 20;77(4):723-733.e6
pubmed: 31932164
Biochem J. 2020 Jun 26;477(12):2401-2419
pubmed: 32519742
BMC Bioinformatics. 2015 Oct 23;16:336
pubmed: 26493560
Nucleic Acids Res. 2014 Jan;42(1):20-44
pubmed: 24068554
PLoS Biol. 2014 Oct 28;12(10):e1001977
pubmed: 25350732
Nucleic Acids Res. 2014 Jul;42(12):7489-527
pubmed: 24878924
Science. 2021 Jul 30;373(6554):
pubmed: 34326207
Bioinformatics. 2017 Sep 15;33(18):2938-2940
pubmed: 28645171
Sci Adv. 2020 Jul 29;6(31):eabb6651
pubmed: 32923609
Nucleic Acids Res. 2021 Nov 8;49(19):11257-11273
pubmed: 34657954
J Mol Biol. 1993 Sep 5;233(1):123-38
pubmed: 8377180
Nat Methods. 2009 May;6(5):343-5
pubmed: 19363495
Nucleic Acids Res. 2014 Jan;42(1):56-69
pubmed: 23990325
Cell. 2021 Nov 11;184(23):5728-5739.e16
pubmed: 34644530
J Mol Biol. 2018 Apr 13;430(8):1141-1156
pubmed: 29518409