Mol Syst Biol. 2013 Nov 19;9:708. doi: 10.1038/msb.2013.62.
Metabolic reconstruction identifies strain-specific regulation of virulence in Toxoplasma gondii
Source
1] Program in Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
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.
- PMID:
- 24247825
- [PubMed - in process]
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