Metabolic fluxes for nutritional flexibility of Mycobacterium tuberculosis.
Mycobacterium tuberculosis
chemostat
metabolic flux
metabolism
tuberculosis
Journal
Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
30
03
2021
received:
08
02
2021
accepted:
31
03
2021
entrez:
4
5
2021
pubmed:
5
5
2021
medline:
5
1
2022
Statut:
ppublish
Résumé
The co-catabolism of multiple host-derived carbon substrates is required by Mycobacterium tuberculosis (Mtb) to successfully sustain a tuberculosis infection. However, the metabolic plasticity of this pathogen and the complexity of the metabolic networks present a major obstacle in identifying those nodes most amenable to therapeutic interventions. It is therefore critical that we define the metabolic phenotypes of Mtb in different conditions. We applied metabolic flux analysis using stable isotopes and lipid fingerprinting to investigate the metabolic network of Mtb growing slowly in our steady-state chemostat system. We demonstrate that Mtb efficiently co-metabolises either cholesterol or glycerol, in combination with two-carbon generating substrates without any compartmentalisation of metabolism. We discovered that partitioning of flux between the TCA cycle and the glyoxylate shunt combined with a reversible methyl citrate cycle is the critical metabolic nodes which underlie the nutritional flexibility of Mtb. These findings provide novel insights into the metabolic architecture that affords adaptability of bacteria to divergent carbon substrates and expand our fundamental knowledge about the methyl citrate cycle and the glyoxylate shunt.
Identifiants
pubmed: 33943004
doi: 10.15252/msb.202110280
pmc: PMC8094261
doi:
Substances chimiques
Glyoxylates
0
Carbon
7440-44-0
Cholesterol
97C5T2UQ7J
glyoxylic acid
JQ39C92HH6
Glycerol
PDC6A3C0OX
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
e10280Subventions
Organisme : Medical Research Council
ID : MR/K01224X/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/T007648/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/C/00004976
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 088677/Z/09/Z
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : P01 AI095208
Pays : United States
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/C/00004559
Pays : United Kingdom
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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