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PLoS Comput Biol. 2018 Jan 4;14(1):e1005895. doi: 10.1371/journal.pcbi.1005895. eCollection 2018 Jan.

Functional interrogation of Plasmodium genus metabolism identifies species- and stage-specific differences in nutrient essentiality and drug targeting.

Author information

1
King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Centre (CBRC), Thuwal, Saudi Arabia.
2
King Abdullah University of Science and Technology (KAUST), Biological and Environmental Sciences and Engineering (BESE) division, Thuwal, Saudi Arabia.
3
Department of Bioengineering, University of California, San Diego, La Jolla, CA, United States of America.
4
Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego School of Medicine, La Jolla, CA, United States of America.
5
Department of Pediatrics, University of California, San Diego, La Jolla, CA, United States of America.
6
Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA, United States of America.
7
Department of Radiological Sciences, University of California, Los Angeles, CA, United States of America.

Abstract

Several antimalarial drugs exist, but differences between life cycle stages among malaria species pose challenges for developing more effective therapies. To understand the diversity among stages and species, we reconstructed genome-scale metabolic models (GeMMs) of metabolism for five life cycle stages and five species of Plasmodium spanning the blood, transmission, and mosquito stages. The stage-specific models of Plasmodium falciparum uncovered stage-dependent changes in central carbon metabolism and predicted potential targets that could affect several life cycle stages. The species-specific models further highlight differences between experimental animal models and the human-infecting species. Comparisons between human- and rodent-infecting species revealed differences in thiamine (vitamin B1), choline, and pantothenate (vitamin B5) metabolism. Thus, we show that genome-scale analysis of multiple stages and species of Plasmodium can prioritize potential drug targets that could be both anti-malarials and transmission blocking agents, in addition to guiding translation from non-human experimental disease models.

PMID:
29300748
PMCID:
PMC5771636
DOI:
10.1371/journal.pcbi.1005895
[Indexed for MEDLINE]
Free PMC Article

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