Email updates

Keep up to date with the latest news and content from BMC Genomics and BioMed Central.

Open Access Research article

Dynamic RNA profiling in Plasmodium falciparum synchronized blood stages exposed to lethal doses of artesunate

Onguma Natalang13, Emmanuel Bischoff2, Guillaume Deplaine1, Caroline Proux2, Marie-Agnès Dillies2, Odile Sismeiro2, Ghislaine Guigon2, Serge Bonnefoy1, Jintana Patarapotikul3, Odile Mercereau-Puijalon1, Jean-Yves Coppée2 and Peter H David1*

Author Affiliations

1 Institut Pasteur, Unité d'Immunologie Moléculaire des Parasites; CNRS URA 2581, 28 Rue du Docteur Roux, F-75724, Paris, Cedex 15, France

2 Institut Pasteur, Plate-Forme 2 – Puces à ADN, 28 Rue du Docteur Roux, F-75724, Paris, Cedex 15, France

3 Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok, 10400, Thailand

For all author emails, please log on.

BMC Genomics 2008, 9:388  doi:10.1186/1471-2164-9-388

Published: 18 August 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.