Modeling metabolism and stage-specific growth of Plasmodium falciparum HB3 during the intraerythrocytic developmental cycle.
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Date
2014-08-27
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Abstract
The human malaria parasite Plasmodium falciparum goes through a complex life cycle including a roughly 48 hour long intraerythrocytic developmental cycle IDC in human red blood cells A better understanding of the metabolic processes required during the asexual blood stage reproduction will enhance our basic knowledge of P falciparum and help identify critical metabolic reactions and pathways associated with blood stage malaria We developed a metabolic network model that mechanistically links time dependent gene expression metabolism and stage specific growth allowing us to predict the metabolic fluxes the biomass production rates and the timing of production of the different biomass components during the IDC We predicted time and stage specific production of precursors and macromolecules for P falciparum strain HB3 allowing us to link specific metabolites to specific physiological functions For example we hypothesized that coenzyme A might be involved in late IDC DNA replication and cell division Moreover the predicted ATP metabolism indicated that energy was mainly produced from glycolysis and utilized for non metabolic processes Finally we used the model to classify the entire tricarboxylic acid cycle into segments each with a distinct function such as superoxide detoxification glutamate glutamine processing and metabolism of fumarate as a byproduct of purine biosynthesis By capturing the normal metabolic and growth progression in P falciparum during the IDC our model provides a starting point for further elucidation of strain specific metabolic activity host parasite interactions stress induced metabolic responses and metabolic responses to antimalarial drugs and drug candidates