Dual metabolomic profiling uncovers Toxoplasma manipulation of the host metabolome and the discovery of a novel parasite metabolic capability.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
19
06
2019
accepted:
25
02
2020
revised:
17
04
2020
pubmed:
8
4
2020
medline:
28
7
2020
entrez:
8
4
2020
Statut:
epublish
Résumé
The obligate intracellular parasite Toxoplasma gondii is auxotrophic for several key metabolites and must scavenge these from the host. It is unclear how T. gondii manipulates host metabolism to support its overall growth rate and non-essential metabolites. To investigate this question, we measured changes in the joint host-parasite metabolome over a time course of infection. Host and parasite transcriptomes were simultaneously generated to determine potential changes in expression of metabolic enzymes. T. gondii infection changed metabolite abundance in multiple metabolic pathways, including the tricarboxylic acid cycle, the pentose phosphate pathway, glycolysis, amino acid synthesis, and nucleotide metabolism. Our analysis indicated that changes in some pathways, such as the tricarboxylic acid cycle, were mirrored by changes in parasite transcription, while changes in others, like the pentose phosphate pathway, were paired with changes in both the host and parasite transcriptomes. Further experiments led to the discovery of a T. gondii enzyme, sedoheptulose bisphosphatase, which funnels carbon from glycolysis into the pentose phosphate pathway through an energetically driven dephosphorylation reaction. This additional route for ribose synthesis appears to resolve the conflict between the T. gondii tricarboxylic acid cycle and pentose phosphate pathway, which are both NADP+ dependent. Sedoheptulose bisphosphatase represents a novel step in T. gondii central carbon metabolism that allows T. gondii to energetically-drive ribose synthesis without using NADP+.
Identifiants
pubmed: 32255806
doi: 10.1371/journal.ppat.1008432
pii: PPATHOGENS-D-19-01100
pmc: PMC7164669
doi:
Substances chimiques
Amino Acids
0
NADP
53-59-8
Ribose
681HV46001
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
e1008432Subventions
Organisme : NIAID NIH HHS
ID : R01 AI144016
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI114277
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI055397
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI078985
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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