Metabolic reconstruction identifies strain-specific regulation of virulence in Toxoplasma gondii.
Identifieur interne : 000D35 ( Main/Exploration ); précédent : 000D34; suivant : 000D36Metabolic reconstruction identifies strain-specific regulation of virulence in Toxoplasma gondii.
Auteurs : Carl Song [Canada] ; Melissa A. Chiasson ; Nirvana Nursimulu ; Stacy S. Hung ; James Wasmuth ; Michael E. Grigg ; John ParkinsonSource :
- Molecular systems biology [ 1744-4292 ] ; 2013.
English descriptors
- KwdEn :
- Antiprotozoal Agents (pharmacology), Diphosphonates (pharmacology), Drug Resistance (drug effects), Fibroblasts (cytology), Fibroblasts (parasitology), Gene Expression Regulation, Host Specificity, Host-Parasite Interactions, Humans, Metabolic Engineering, Metabolic Networks and Pathways, Models, Genetic, Quinolines (pharmacology), Species Specificity, Toxoplasma (drug effects), Toxoplasma (genetics), Toxoplasma (metabolism), Toxoplasma (pathogenicity), Virulence.
- MESH :
- chemical , pharmacology : Antiprotozoal Agents, Diphosphonates, Quinolines.
- cytology : Fibroblasts.
- drug effects : Drug Resistance, Toxoplasma.
- genetics : Toxoplasma.
- metabolism : Toxoplasma.
- parasitology : Fibroblasts.
- pathogenicity : Toxoplasma.
- Gene Expression Regulation, Host Specificity, Host-Parasite Interactions, Humans, Metabolic Engineering, Metabolic Networks and Pathways, Models, Genetic, Species Specificity, Virulence.
Abstract
Increasingly, metabolic potential is proving to be a critical determinant governing a pathogen's virulence as well as its capacity to expand its host range. To understand the potential contribution of metabolism to strain-specific infectivity differences, we present a constraint-based metabolic model of the opportunistic parasite, Toxoplasma gondii. Dominated by three clonal strains (Type I, II, and III demonstrating distinct virulence profiles), T. gondii exhibits a remarkably broad host range. Integrating functional genomic data, our model (which we term as iCS382) reveals that observed strain-specific differences in growth rates are driven by altered capacities for energy production. We further predict strain-specific differences in drug susceptibilities and validate one of these predictions in a drug-based assay, with a Type I strain demonstrating resistance to inhibitors that are effective against a Type II strain. We propose that these observed differences reflect an evolutionary strategy that allows the parasite to extend its host range, as well as result in a subsequent partitioning into discrete strains that display altered virulence profiles across different hosts, different organs, and even cell types.
DOI: 10.1038/msb.2013.62
PubMed: 24247825
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en">Increasingly, metabolic potential is proving to be a critical determinant governing a pathogen's virulence as well as its capacity to expand its host range. To understand the potential contribution of metabolism to strain-specific infectivity differences, we present a constraint-based metabolic model of the opportunistic parasite, Toxoplasma gondii. Dominated by three clonal strains (Type I, II, and III demonstrating distinct virulence profiles), T. gondii exhibits a remarkably broad host range. Integrating functional genomic data, our model (which we term as iCS382) reveals that observed strain-specific differences in growth rates are driven by altered capacities for energy production. We further predict strain-specific differences in drug susceptibilities and validate one of these predictions in a drug-based assay, with a Type I strain demonstrating resistance to inhibitors that are effective against a Type II strain. We propose that these observed differences reflect an evolutionary strategy that allows the parasite to extend its host range, as well as result in a subsequent partitioning into discrete strains that display altered virulence profiles across different hosts, different organs, and even cell types.</div>
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<name sortKey="Hung, Stacy S" sort="Hung, Stacy S" uniqKey="Hung S" first="Stacy S" last="Hung">Stacy S. Hung</name>
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