The conserved transcriptional regulator CdnL is required for metabolic homeostasis and morphogenesis in Caulobacter.
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
15
07
2019
accepted:
01
01
2020
revised:
31
01
2020
pubmed:
22
1
2020
medline:
14
4
2020
entrez:
22
1
2020
Statut:
epublish
Résumé
Bacterial growth and division require regulated synthesis of the macromolecules used to expand and replicate components of the cell. Transcription of housekeeping genes required for metabolic homeostasis and cell proliferation is guided by the sigma factor σ70. The conserved CarD-like transcriptional regulator, CdnL, associates with promoter regions where σ70 localizes and stabilizes the open promoter complex. However, the contributions of CdnL to metabolic homeostasis and bacterial physiology are not well understood. Here, we show that Caulobacter crescentus cells lacking CdnL have severe morphological and growth defects. Specifically, ΔcdnL cells grow slowly in both rich and defined media, and are wider, more curved, and have shorter stalks than WT cells. These defects arise from transcriptional downregulation of most major classes of biosynthetic genes, leading to significant decreases in the levels of critical metabolites, including pyruvate, α-ketoglutarate, ATP, NAD+, UDP-N-acetyl-glucosamine, lipid II, and purine and pyrimidine precursors. Notably, we find that ΔcdnL cells are glutamate auxotrophs, and ΔcdnL is synthetic lethal with other genetic perturbations that limit glutamate synthesis and lipid II production. Our findings implicate CdnL as a direct and indirect regulator of genes required for metabolic homeostasis that impacts morphogenesis through availability of lipid II and other metabolites.
Identifiants
pubmed: 31961855
doi: 10.1371/journal.pgen.1008591
pii: PGENETICS-D-19-01152
pmc: PMC6994171
doi:
Substances chimiques
Bacterial 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
e1008591Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM008515
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007445
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM111706
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM108640
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM130320
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Anal Chem. 2010 Dec 1;82(23):9818-26
pubmed: 21049934
Nat Chem Biol. 2017 Jul;13(7):793-798
pubmed: 28553948
Nucleic Acids Res. 2012 May;40(10):4288-97
pubmed: 22287627
Infect Immun. 2008 Oct;76(10):4439-44
pubmed: 18663002
Emerg Microbes Infect. 2018 Jul 9;7(1):126
pubmed: 29985409
Annu Rev Microbiol. 2011;65:37-55
pubmed: 21639785
Brief Bioinform. 2013 Mar;14(2):178-92
pubmed: 22517427
J Bacteriol. 2000 Jan;182(2):337-47
pubmed: 10629178
Elife. 2014 Nov 25;3:
pubmed: 25421297
J Bacteriol. 2010 Jul;192(14):3678-88
pubmed: 20472802
Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):12619-24
pubmed: 23858468
Bioinformatics. 2010 Mar 1;26(5):589-95
pubmed: 20080505
PLoS One. 2013;8(2):e57579
pubmed: 23469030
J Bacteriol. 2012 Oct;194(20):5621-31
pubmed: 22904282
J Bacteriol. 2004 Mar;186(5):1448-61
pubmed: 14973021
Proc Natl Acad Sci U S A. 2019 Jul 2;116(27):13573-13581
pubmed: 31217290
J Microsc. 2007 Aug;227(Pt 2):140-56
pubmed: 17845709
J Bacteriol. 1998 Oct;180(19):5235-9
pubmed: 9748460
Mol Microbiol. 2006 Jan;59(2):386-401
pubmed: 16390437
EMBO J. 2009 May 6;28(9):1208-19
pubmed: 19279668
PLoS One. 2016 Feb 05;11(2):e0148670
pubmed: 26849219
EMBO J. 2015 Jul 2;34(13):1786-800
pubmed: 25953831
Curr Opin Microbiol. 2006 Apr;9(2):167-72
pubmed: 16458044
Trends Microbiol. 2017 Aug;25(8):673-687
pubmed: 28359631
mBio. 2015 Jul 28;6(4):e00952
pubmed: 26220966
Genome Biol. 2003;4(5):P3
pubmed: 12734009
Nat Commun. 2015 Jun 23;6:7281
pubmed: 26099469
Sci Rep. 2017 Feb 24;7:43240
pubmed: 28233804
J Bacteriol. 2016 Oct 21;198(22):3070-3079
pubmed: 27573014
Nucleic Acids Res. 2010 Aug;38(14):4586-98
pubmed: 20371514
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
J Bacteriol. 1993 May;175(10):2970-9
pubmed: 8098327
Philos Trans R Soc Lond B Biol Sci. 2015 Oct 5;370(1679):
pubmed: 26370943
Cell. 2009 Jul 10;138(1):146-59
pubmed: 19596241
Mol Microbiol. 2017 Sep;105(5):721-740
pubmed: 28613431
Front Microbiol. 2015 May 08;6:449
pubmed: 26005443
J Bacteriol. 2017 May 9;199(11):
pubmed: 28320879
mBio. 2019 Jul 9;10(4):
pubmed: 31289173
BMC Bioinformatics. 2016 Oct 8;17(1):419
pubmed: 27717304
Microbios. 1976;16(65-66):219-26
pubmed: 18652
Nat Biotechnol. 2011 Jan;29(1):24-6
pubmed: 21221095
Methods Mol Biol. 2016;1440:11-27
pubmed: 27311661
J Bacteriol. 1978 Sep;135(3):1141-5
pubmed: 690072
Nat Rev Microbiol. 2011 Dec 28;10(2):123-36
pubmed: 22203377
Mol Microbiol. 2013 Jul;89(1):1-13
pubmed: 23679048
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
PLoS One. 2014 Oct 01;9(10):e108946
pubmed: 25272012
PLoS Genet. 2017 Aug 21;13(8):e1006978
pubmed: 28827812
Mol Microbiol. 1995 Aug;17(3):421-6
pubmed: 8559061
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
J Bacteriol. 2007 Mar;189(5):2181-5
pubmed: 17172333
Mol Microbiol. 2016 Apr;100(1):1-14
pubmed: 26593043
Chem Biol. 2009 May 29;16(5):548-56
pubmed: 19477419