ArticlePLoS computational biology2017
Bioenergetics-based modeling of Plasmodium falciparum metabolism reveals its essential genes, nutritional requirements, and thermodynamic bottlenecks.
Article in PLoS computational biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed.
- In silico analysis and comparison of the metabolic capabilities of different organisms by reducing metabolic complexity.Microbiome · 2026Article
- Metabolic network reconstruction as a resource for analyzing Salmonella Typhimurium SL1344 growth in the mouse intestine.PLoS computational biology · 2025Article
- Host cell CRISPR genomics and modelling reveal shared metabolic vulnerabilities in the intracellular development of Plasmodium falciparum and related hemoparasites.Nature communications · 2024Article
- A workflow for annotating the knowledge gaps in metabolic reconstructions using known and hypothetical reactions.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Comparative analyses of parasites with a comprehensive database of genome-scale metabolic models.PLoS computational biology · 2022Article
- Dominique Soldati-Favre: BringingFrontiers in cellular and infection microbiology · 2022Article
- Compounds targeting GPI biosynthesis orComputational and structural biotechnology journal · 2022Article
- Reaction lumping in metabolic networks for application with thermodynamic metabolic flux analysis.Scientific reports · 2021Article
- PhenoMapping: a protocol to map cellular phenotypes to metabolic bottlenecks, identify conditional essentiality, and curate metabolic models.STAR protocols · 2021Article
- Amino Acid Metabolism in Apicomplexan Parasites.Metabolites · 2021Review
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- Analysis of human metabolism by reducing the complexity of the genome-scale models using redHUMAN.Nature communications · 2020Article
- Vitamin and cofactor acquisition in apicomplexans: SynthesisThe Journal of biological chemistry · 2020Review
- Mechanistic insights into bacterial metabolic reprogramming from omics-integrated genome-scale models.NPJ systems biology and applications · 2020Article
- Large-scale kinetic metabolic models ofBiotechnology for biofuels · 2020Article
- Mining the Human Host Metabolome Toward an Improved Understanding of Malaria Transmission.Frontiers in microbiology · 2020Review
- Article
- Computational Identification of Metabolic Pathways ofInternational journal of genomics · 2019Article
- pyTFA and matTFA: a Python package and a Matlab toolbox for Thermodynamics-based Flux Analysis.Bioinformatics (Oxford, England) · 2019Article
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5 authors.
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Abstract
Novel antimalarial therapies are urgently needed for the fight against drug-resistant parasites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this complexity and allow integrative analyses of cell metabolism. In this study, we present a genome-scale metabolic model (iPfa) of the deadliest malaria parasite, Plasmodium falciparum, and its thermodynamics-based flux analysis (TFA). Using previous absolute concentration data of the intraerythrocytic parasite, we applied TFA to iPfa and predicted up to 63 essential genes and 26 essential pairs of genes. Of the 63 genes, 35 have been experimentally validated and reported in the literature, and 28 have not been experimentally tested and include previously hypothesized or novel predictions of essential metabolic capabilities. Without metabolomics data, four of the genes would have been incorrectly predicted to be non-essential. TFA also indicated that substrate channeling should exist in two metabolic pathways to ensure the thermodynamic feasibility of the flux. Finally, analysis of the metabolic capabilities of P. falciparum led to the identification of both the minimal nutritional requirements and the genes that can become indispensable upon substrate inaccessibility. This model provides novel insight into the metabolic needs and capabilities of the malaria parasite and highlights metabolites and pathways that should be measured and characterized to identify potential thermodynamic bottlenecks and substrate channeling. The hypotheses presented seek to guide experimental studies to facilitate a better understanding of the parasite metabolism and the identification of targets for more efficient intervention.
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