| 2008 |
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| Dynamic RNA profiling in Plasmodium falciparum synchronized blood stages exposed to
lethal doses of artesunate. |
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| Natalang, O., Bischoff, E., Deplaine, G., Proux, C., Dillies, M. A., Sismeiro, O., Guigon, G.,
Bonnefoy, S., Patarapotikul, J., Mercereau-Puijalon, O., Coppee, J. Y., and David, P. H. |
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| Institut Pasteur, Unite d'Immunologie Moleculaire des Parasites, CNRS URA 2581, 28 Rue du
Docteur Roux, F-75724, Paris, Cedex 15, France onguma382@yahoocom |
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| 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 |
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| Published in:BMC.Genomics 9, 388. 2008. |
