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Title: Dynamic RNA profiling in Plasmodium falciparum synchronized blood stages exposed to lethal doses of artesunate
Authors: Onguma Natalang
Emmanuel Bischoff
Guillaume Deplaine
Caroline Proux
Marie Agnès Dillies
Odile Sismeiro
Ghislaine Guigon
Serge Bonnefoy
Jintana Patarapotikul
Odile Mercereau-Puijalon
Jean Yves Coppée
Peter H. David
CNRS Centre National de la Recherche Scientifique
Institut Pasteur, Paris
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 18-Aug-2008
Citation: BMC Genomics. Vol.9, (2008)
Abstract: Background: Translation of the genome sequence of Plasmodium sp. into biologically relevant information relies on high through-put genomics technology which includes transcriptome analysis. However, few studies to date have used this powerful approach to explore transcriptome alterations of P. falciparum parasites exposed to antimalarial drugs. Results: The rapid action of artesunate allowed us to study dynamic changes of the parasite transcriptome in synchronous parasite cultures exposed to the drug for 90 minutes and 3 hours. Developmentally regulated genes were filtered out, leaving 398 genes which presented altered transcript levels reflecting drug-exposure. Few genes related to metabolic pathways, most encoded chaperones, transporters, kinases, Zn-finger proteins, transcription activating proteins, proteins involved in proteasome degradation, in oxidative stress and in cell cycle regulation. A positive bias was observed for over-expressed genes presenting a subtelomeric location, allelic polymorphism and encoding proteins with potential export sequences, which often belonged to subtelomeric multi-gene families. This pointed to the mobilization of processes shaping the interface between the parasite and its environment. In parallel, pathways were engaged which could lead to parasite death, such as interference with purine/pyrimidine metabolism, the mitochondrial electron transport chain, proteasome-dependent protein degradation or the integrity of the food vacuole. Conclusion: The high proportion of over-expressed genes encoding proteins exported from the parasite highlight the importance of extra-parasitic compartments as fields for exploration in drug research which, to date, has mostly focused on the parasite itself rather than on its intra and extra erythrocytic environment. Further work is needed to clarify which transcriptome alterations observed reflect a specific response to overcome artesunate toxicity or more general perturbations on the path to cellular death. © 2008 Natalang et al; licensee BioMed Central Ltd.
ISSN: 14712164
Appears in Collections:Scopus 2006-2010

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