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Dynamic RNA profiling in Plasmodium falciparum synchronized blood stages exposed to lethal doses of artesunate.
- Source :
-
BMC genomics [BMC Genomics] 2008 Aug 18; Vol. 9, pp. 388. Date of Electronic Publication: 2008 Aug 18. - Publication Year :
- 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.<br />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.<br />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.
- Subjects :
- Analysis of Variance
Animals
Artesunate
Cells, Cultured
Gene Expression Profiling
Gene Expression Regulation drug effects
Genes, Protozoan drug effects
Life Cycle Stages
Oligonucleotide Array Sequence Analysis
Plasmodium falciparum growth & development
RNA, Protozoan genetics
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Antimalarials pharmacology
Artemisinins pharmacology
Plasmodium falciparum drug effects
Plasmodium falciparum genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2164
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- BMC genomics
- Publication Type :
- Academic Journal
- Accession number :
- 18706115
- Full Text :
- https://doi.org/10.1186/1471-2164-9-388