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| Status |
Public on Nov 15, 2008 |
| Title |
Hard-wiring in the Plasmodium falciparum transcriptome I |
| Organism |
Plasmodium falciparum |
| Experiment type |
Expression profiling by array
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| Summary |
To help malaria parasites survive unpredictable host immune responses, it is known that genes for surface proteins express stochastically in Plasmodium falciparum. Here, we demonstrate that gene expression for intracellular metabolic functions may be preordained and insensitive to specific metabolic perturbations. In a tightly-controlled, large microarray study involving over 100 hybridizations to isogenic drug-sensitive and drug-resistant parasites, the lethal antifolate WR99210 failed to over-produce RNA for the biochemically and genetically proven target dihydrofolate reductase-thymidylate synthase (DHFR-TS). Beyond the target, this transcriptional obstinacy carried over to the rest of the parasite genome, including genes for target pathways of folate and pyrimidine metabolism. Even 12 hours after commitment to death, the transcriptome remained faithful to evolutionarily entrained paths. A system-wide transcriptional disregard for metabolic perturbations in malaria parasites may contribute to selective vulnerabilities of the parasite to lethal antimetabolites. While large protective metabolic responses were not detected, DNA microarrays helped capture small, but reproducible drug-dependent perturbations within hours of drug exposure. In addition, in Plasmodium cells that had adapted to long-term drug exposure, DNA microarrays revealed new, large genome-wide transcriptional adjustments in the hard-wired transcriptional program itself.
Keywords: Plasmodium falciparum treated with WR99210
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| Overall design |
RNA from P. falciparum Dd2 and B1G9 (WR99210 resistant cell-line) trophozoites that had been treated with 10 nM WR99210 for varying durations (3, 6, 9, 15, 18, 21 and 24h) was hybridized against a common pool of trophozoite RNA from a cognate clone, a culture containing 0.1% (v/v) DMSO lacking drug was used as untreated control, microarray data were obtained from at least four hybridizations using RNA from two independent parasite cultures
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| Contributor(s) |
Ganessan K, Ponmee N, Jiang L, Fowble J, White J, Kamchonwongpaisan S, Yuthavong Y, Wilairat P, Rathod PK |
| Citation(s) |
19023412 |
| Submission date |
Nov 28, 2007 |
| Last update date |
Mar 17, 2012 |
| Contact name |
Pradipsinh K Rathod |
| E-mail(s) |
rathod@chem.washington.edu
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| Organization name |
University of Washington
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| Department |
Chemistry
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| Lab |
Rathod
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| Street address |
Campus Box 351700
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98195 |
| Country |
USA |
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| Platforms (1) |
| GPL6187 |
Plasmodium falciparum Rathod Lab 8096 |
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| Samples (123)
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| Relations |
| BioProject |
PRJNA103637 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE9724_RAW.tar |
67.6 Mb |
(http)(custom) |
TAR (of GPR) |
| Processed data included within Sample table |
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