Synthetic genetic oscillators demonstrate the functional importance of phenotypic variation in pneumococcal-host interactions.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 Nov 2023
17 Nov 2023
Historique:
received:
02
06
2023
accepted:
03
11
2023
medline:
27
11
2023
pubmed:
18
11
2023
entrez:
17
11
2023
Statut:
epublish
Résumé
Phenotypic variation is the phenomenon in which clonal cells display different traits even under identical environmental conditions. This plasticity is thought to be important for processes including bacterial virulence, but direct evidence for its relevance is often lacking. For instance, variation in capsule production in the human pathogen Streptococcus pneumoniae has been linked to different clinical outcomes, but the exact relationship between variation and pathogenesis is not well understood due to complex natural regulation. In this study, we use synthetic oscillatory gene regulatory networks (GRNs) based on CRISPR interference (CRISPRi) together with live cell imaging and cell tracking within microfluidics devices to mimic and test the biological function of bacterial phenotypic variation. We provide a universally applicable approach for engineering intricate GRNs using only two components: dCas9 and extended sgRNAs (ext-sgRNAs). Our findings demonstrate that variation in capsule production is beneficial for pneumococcal fitness in traits associated with pathogenesis providing conclusive evidence for this longstanding question.
Identifiants
pubmed: 37978173
doi: 10.1038/s41467-023-43241-y
pii: 10.1038/s41467-023-43241-y
pmc: PMC10656556
doi:
Substances chimiques
RNA, Guide, CRISPR-Cas Systems
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7454Subventions
Organisme : NIAID NIH HHS
ID : R01 AI038446
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150893
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI038446
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023. The Author(s).
Références
Nat Commun. 2020 Jun 2;11(1):2746
pubmed: 32488086
Mol Syst Biol. 2017 May 10;13(5):931
pubmed: 28490437
J Bacteriol. 2006 Nov;188(22):7785-95
pubmed: 16936041
mBio. 2022 Oct 19;13(6):e0221222
pubmed: 36259726
Nature. 2013 Feb 21;494(7437):353-6
pubmed: 23426324
Curr Opin Microbiol. 2015 Oct;27:25-36
pubmed: 26143306
ACS Synth Biol. 2016 Jan 15;5(1):81-8
pubmed: 26390083
Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27608-27619
pubmed: 33087560
J Infect Dis. 1998 Feb;177(2):368-77
pubmed: 9466523
Mol Microbiol. 2020 Jan;113(1):297-308
pubmed: 31693257
Curr Biol. 2010 Jun 22;20(12):1099-103
pubmed: 20537537
Nature. 2008 Aug 21;454(7207):987-90
pubmed: 18719588
Nucleic Acids Res. 2020 Aug 20;48(14):8165-8177
pubmed: 32609820
PLoS Pathog. 2023 Jan 31;19(1):e1011035
pubmed: 36719895
Clin Microbiol Rev. 2015 Jul;28(3):871-99
pubmed: 26085553
Lancet Infect Dis. 2004 Mar;4(3):144-54
pubmed: 14998500
Nat Commun. 2023 Nov 17;14(1):7454
pubmed: 37978173
Curr Opin Microbiol. 2021 Dec;64:76-81
pubmed: 34634678
PLoS Pathog. 2014 Aug 28;10(8):e1004339
pubmed: 25166617
ACS Synth Biol. 2015 Mar 20;4(3):228-39
pubmed: 24845455
Infect Immun. 2015 May;83(5):1957-72
pubmed: 25733517
Front Microbiol. 2017 Mar 07;8:277
pubmed: 28326061
Infect Immun. 2005 Aug;73(8):4653-67
pubmed: 16040978
Lancet. 2023 Dec 17;400(10369):2221-2248
pubmed: 36423648
Infect Immun. 2010 Feb;78(2):704-15
pubmed: 19948837
J Mol Biol. 2016 Feb 27;428(5 Pt B):928-44
pubmed: 26546279
F1000Res. 2019 Oct 21;8:
pubmed: 31737252
Microbiol Spectr. 2022 Jun 29;10(3):e0091622
pubmed: 35536022
Front Bioeng Biotechnol. 2022 Jan 28;9:743950
pubmed: 35155399
PLoS Biol. 2014 Aug 19;12(8):e1001928
pubmed: 25136970
Nucleic Acids Res. 2013 Aug;41(15):7429-37
pubmed: 23761437
Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2203011119
pubmed: 35858437
Infect Immun. 2014 Feb;82(2):694-705
pubmed: 24478084
Nature. 2000 Jan 20;403(6767):335-8
pubmed: 10659856
Nat Rev Microbiol. 2016 Mar;14(3):135-49
pubmed: 26876034
mSphere. 2017 Sep 13;2(5):
pubmed: 28932816
Annu Rev Microbiol. 2008;62:193-210
pubmed: 18537474
PLoS Pathog. 2020 May 21;16(5):e1008439
pubmed: 32437427
Nucleic Acids Res. 2018 Nov 2;46(19):9971-9989
pubmed: 30107613
Nat Methods. 2019 Dec;16(12):1226-1232
pubmed: 31570887
Cell Host Microbe. 2021 Jan 13;29(1):107-120.e6
pubmed: 33120116
Trends Microbiol. 2019 Jan;27(1):64-74
pubmed: 30243514
PLoS Biol. 2007 Oct;5(10):2177-89
pubmed: 17760501
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Biochem Soc Trans. 2019 Dec 20;47(6):1795-1804
pubmed: 31803907
Sci Rep. 2016 Jul 08;6:29255
pubmed: 27386955
PLoS Pathog. 2020 Mar 18;16(3):e1008417
pubmed: 32187228
Cell Rep. 2018 Nov 27;25(9):2390-2400.e3
pubmed: 30485808
Nat Rev Microbiol. 2015 Aug;13(8):497-508
pubmed: 26145732
Virulence. 2021 Dec;12(1):2366-2381
pubmed: 34506260
Infect Immun. 1994 Jun;62(6):2582-9
pubmed: 8188381
Cell. 2013 Feb 28;152(5):1173-83
pubmed: 23452860
Appl Environ Microbiol. 2003 Dec;69(12):7480-91
pubmed: 14660401
J Bacteriol. 2014 Jun;196(11):1992-2003
pubmed: 24659769
Mol Microbiol. 2021 Sep;116(3):996-1008
pubmed: 34328238
Front Cell Infect Microbiol. 2019 Dec 11;9:421
pubmed: 31921700
Infect Immun. 2018 Feb 20;86(3):
pubmed: 29311231
Curr Opin Chem Biol. 2016 Oct;34:11-19
pubmed: 27236825
PLoS Pathog. 2016 Jul 18;12(7):e1005762
pubmed: 27427949
Nat Commun. 2014 Sep 30;5:5055
pubmed: 25268848
J Mol Biol. 2019 Nov 22;431(23):4645-4655
pubmed: 31260693
Appl Environ Microbiol. 2020 May 5;86(10):
pubmed: 32198170
BMC Biol. 2017 Feb 21;15(1):17
pubmed: 28222723
Trends Biotechnol. 2021 Jan;39(1):59-71
pubmed: 32586633
Microb Drug Resist. 1998 Summer;4(2):129-35
pubmed: 9651000
ACS Synth Biol. 2020 Dec 18;9(12):3377-3387
pubmed: 33231079
Nat Methods. 2022 Jul;19(7):829-832
pubmed: 35654950
Front Cell Infect Microbiol. 2016 Jun 20;6:63
pubmed: 27379215