Identification of a Master Regulator of Differentiation in Toxoplasma.
Toxoplasma gondii
bradyzoite
chronic infection
differentiation
master regulator
single-cell RNA-sequencing
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
23 01 2020
23 01 2020
Historique:
received:
04
06
2019
revised:
28
10
2019
accepted:
10
12
2019
pubmed:
21
1
2020
medline:
24
6
2020
entrez:
21
1
2020
Statut:
ppublish
Résumé
Toxoplasma gondii chronically infects a quarter of the world's population, and its recrudescence can cause life-threatening disease in immunocompromised individuals and recurrent ocular lesions in the immunocompetent. Acute-stage tachyzoites differentiate into chronic-stage bradyzoites, which form intracellular cysts resistant to immune clearance and existing therapies. The molecular basis of this differentiation is unknown, despite being efficiently triggered by stresses in culture. Through Cas9-mediated screening and single-cell profiling, we identify a Myb-like transcription factor (BFD1) necessary for differentiation in cell culture and in mice. BFD1 accumulates during stress and its synthetic expression is sufficient to drive differentiation. Consistent with its function as a transcription factor, BFD1 binds the promoters of many stage-specific genes and represents a counterpoint to the ApiAP2 factors that dominate our current view of parasite gene regulation. BFD1 provides a genetic switch to study and control Toxoplasma differentiation and will inform prevention and treatment of chronic infections.
Identifiants
pubmed: 31955846
pii: S0092-8674(19)31375-3
doi: 10.1016/j.cell.2019.12.013
pmc: PMC6978799
pii:
doi:
Substances chimiques
Protozoan Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
359-372.e16Subventions
Organisme : NIAID NIH HHS
ID : R01 AI080621
Pays : United States
Organisme : NIGMS NIH HHS
ID : DP2 GM119419
Pays : United States
Organisme : NIH HHS
ID : DP5 OD017892
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI089992
Pays : United States
Organisme : NIAID NIH HHS
ID : U24 AI118672
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
Références
Immunity. 2009 Nov 20;31(5):772-86
pubmed: 19896394
Mol Microbiol. 2008 Jun;68(6):1502-18
pubmed: 18433450
J Mol Biol. 2005 Feb 11;346(1):29-42
pubmed: 15663925
Eukaryot Cell. 2004 Aug;3(4):992-1003
pubmed: 15302832
Nat Microbiol. 2018 Nov;3(11):1206-1213
pubmed: 30177743
Elife. 2019 Jun 24;8:
pubmed: 31232687
PLoS Pathog. 2006 Oct;2(10):e105
pubmed: 17069459
Cell Mol Life Sci. 2018 Jul;75(13):2355-2373
pubmed: 29602951
BMC Genomics. 2014 Sep 20;15:806
pubmed: 25240600
Mol Biochem Parasitol. 2011 Mar;176(1):1-7
pubmed: 21126543
Mol Microbiol. 2002 May;44(3):735-47
pubmed: 11994154
Bioinformatics. 2007 Nov 1;23(21):2947-8
pubmed: 17846036
Eukaryot Cell. 2002 Jun;1(3):329-40
pubmed: 12455982
Physiol Mol Biol Plants. 2013 Jul;19(3):307-21
pubmed: 24431500
PLoS Genet. 2013;9(2):e1003305
pubmed: 23437009
Cell. 2015 May 21;161(5):1202-1214
pubmed: 26000488
Infect Immun. 1998 Apr;66(4):1632-7
pubmed: 9529091
Elife. 2017 Jan 16;6:
pubmed: 28079019
Mol Biochem Parasitol. 2001 Jul;115(2):165-75
pubmed: 11420103
BMC Genomics. 2008 Oct 16;9:488
pubmed: 18925949
Mol Biochem Parasitol. 2005 Dec;144(2):159-66
pubmed: 16182390
J Mol Biol. 2013 Apr 26;425(8):1287-301
pubmed: 23454356
Nature. 2017 Nov 2;551(7678):95-99
pubmed: 29094698
Mol Biochem Parasitol. 1999 Apr 30;99(2):223-35
pubmed: 10340486
FEBS J. 2014 Nov;281(22):5077-91
pubmed: 25223457
Mol Biochem Parasitol. 1997 Sep;88(1-2):115-26
pubmed: 9274873
Nat Protoc. 2012 Sep;7(9):1728-40
pubmed: 22936215
mBio. 2017 Jan 10;8(1):
pubmed: 28074022
Infect Immun. 2008 Jun;76(6):2402-10
pubmed: 18347037
J Biol Chem. 1996 Jun 14;271(24):14010-9
pubmed: 8662859
Annu Rev Microbiol. 2018 Sep 08;72:501-519
pubmed: 29975590
Clin Infect Dis. 2015 Jan 15;60(2):271-3
pubmed: 25301214
Plant Reprod. 2019 Mar;32(1):63-75
pubmed: 30719569
Epigenetics Chromatin. 2018 Jun 28;11(1):35
pubmed: 29954426
FEMS Microbiol Lett. 1996 Mar 15;137(1):103-8
pubmed: 8935663
Int J Parasitol. 2004 Mar 9;34(3):347-60
pubmed: 15003495
PLoS One. 2010 Aug 26;5(8):e12354
pubmed: 20865045
Microbes Infect. 2005 Jan;7(1):41-8
pubmed: 15716062
Proc Int Conf Intell Syst Mol Biol. 1994;2:28-36
pubmed: 7584402
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
PLoS Pathog. 2013;9(12):e1003823
pubmed: 24385904
mBio. 2019 Apr 30;10(2):
pubmed: 31040239
Cell Microbiol. 2009 Jun;11(6):898-910
pubmed: 19239479
Cell Host Microbe. 2008 Feb 14;3(2):77-87
pubmed: 18312842
mBio. 2017 Aug 29;8(4):
pubmed: 28851850
Cell. 2006 Sep 8;126(5):995-1004
pubmed: 16959577
PLoS One. 2012;7(2):e29998
pubmed: 22347997
Nucleic Acids Res. 2005 Jul 21;33(13):3994-4006
pubmed: 16040597
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Mol Biochem Parasitol. 1996 May;77(2):235-9
pubmed: 8813669
J Immunol. 1988 Nov 15;141(10):3584-91
pubmed: 3183382
J Mol Evol. 2005 Feb;60(2):257-67
pubmed: 15785854
BMC Biol. 2017 May 19;15(1):44
pubmed: 28526029
Nucleic Acids Res. 2008 Jan;36(Database issue):D553-6
pubmed: 18003657
Mol Microbiol. 2002 Nov;46(4):971-84
pubmed: 12421304
Eukaryot Cell. 2002 Jun;1(3):317-28
pubmed: 12455981
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Eukaryot Cell. 2011 Dec;10(12):1637-47
pubmed: 22021236
Science. 2016 Jun 17;352(6292):1413-6
pubmed: 27313038
Mol Cell. 2010 May 28;38(4):576-89
pubmed: 20513432
Exp Parasitol. 1994 Jun;78(4):361-70
pubmed: 8206135
N Engl J Med. 1992 Dec 3;327(23):1643-8
pubmed: 1359410
Sci Rep. 2019 Feb 6;9(1):1474
pubmed: 30728393
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Dev Cell. 2005 Feb;8(2):153-66
pubmed: 15691758
Nat Biotechnol. 2011 Jan;29(1):24-6
pubmed: 21221095
Mol Biochem Parasitol. 2004 Nov;138(1):159-63
pubmed: 15500927
PLoS One. 2014 Jun 27;9(6):e100450
pubmed: 24971596
PLoS Pathog. 2013;9(12):e1003779
pubmed: 24367253
J Biol Chem. 2008 Jun 13;283(24):16591-601
pubmed: 18420584
Clin Microbiol Rev. 2009 Jul;22(3):508-34
pubmed: 19597012
Nat Microbiol. 2019 Jan;4(1):144-154
pubmed: 30478286
Lancet. 2004 Jun 12;363(9425):1965-76
pubmed: 15194258
Nat Methods. 2017 Apr;14(4):395-398
pubmed: 28192419
BMC Biol. 2005 Dec 02;3:26
pubmed: 16324218
Mol Microbiol. 2002 May;44(3):721-33
pubmed: 11994153
Int J Parasitol. 2004 Mar 9;34(3):323-31
pubmed: 15003493
Clin Microbiol Rev. 1998 Apr;11(2):267-99
pubmed: 9564564
Cell. 2016 Sep 8;166(6):1423-1435.e12
pubmed: 27594426
Nat Biotechnol. 2015 May;33(5):495-502
pubmed: 25867923