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Metabolic reconstruction identifies strain-specific regulation of virulence in Toxoplasma gondii
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 mode...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
European Molecular Biology Organization
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039375/ https://www.ncbi.nlm.nih.gov/pubmed/24247825 http://dx.doi.org/10.1038/msb.2013.62 |
Sumario: | 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. |
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