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E-GEOD-61536 - Plasmodium parasites mount an arrest response against dihydroartemisinin [Microarray]

Status
Released on 15 October 2015, last updated on 24 November 2015
Organism
Plasmodium falciparum
Samples (58)
Array (1)
Protocols (7)
Description
Control of malaria is threatened by emerging parasite resistance to artemisinin drug (ART) therapies. The molecular details of how Plasmodium malaria parasites response to ART and how this relates to resistance is not clear. To determine how parasites respond to ART by altering gene expression, we performed a transcriptomic study of dihydroartemisinin (DHA) response in P. falciparum K1 strain and in P. berghei ANKA strain. Microarray data from DHA-treated P. falciparum trophozoite stage parasites were compared with data from other ART treatments. Genes with consistent changes in expression were identified, which includes notably down-regulation of cytosolic ribosomal protein genes. RNA-seq data revealed a similar pattern of transcriptomic change, although the pattern was much clearer in that more than one-third of P. falciparum trophozoite genes are differentially expressed with greater statistical support for down-regulation of ribosomal protein genes. The poor overlap of differentially-expressed genes between microarray and RNA-seq and less-well defined patterns for the former suggests that the accuracy of microarray is limited by technological bias. The trophozoite response to DHA is overall “ring-like” and less “trophozoite-like”, which is consistent with previous findings that Plasmodium can enter a quiescent ring-like state to resist ART. RNA-seq data from DHA-treated P. falciparum rings reveal a more muted response, although there is considerable overlap of differentially expressed genes with DHA-treated trophozoites. In contrast, P. falciparum schizonts are unresponsive to DHA, suggesting that the protective response acts mainly to arrest parasite development through the G2/M checkpoint. The transcriptional response of P. berghei to DHA treatment in vivo in infected mice is strikingly similar to the P. falciparum in vitro ring and trophozoite responses, in which ribosomal protein genes are notably down-regulated. These results suggest Plasmodium species respond to DHA in the same way. This knowledge could be applied to outwit the parasite to deliver more effective artemisinin therapies, and maybe hinder the development of drug resistance. Two condition drug-treatment experiment, Dihydroartemisinin vs. Vehicle control treatment with matched reference untreated controls. Biological replicates: 5 independently grown and harvested experimental culture replicates. One replicate of treatment/reference time-point per array.
Experiment type
transcription profiling by array 
Contacts
Philip James Shaw <philip@biotec.or.th>, Chairat Uthaipibull, Chayaphat Wongsombat, Jittima Piriyapongsa, Nattida Suwannakitti, Pavita Tipsombatboon, Philip J Shaw, Pongpisid Koonyosying, Sastra Chaothieng, Sumalee Kamchonwongpaisan, Yongyuth Yuthavong
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-61536.idf.txt
Sample and data relationshipE-GEOD-61536.sdrf.txt
Raw data (1)E-GEOD-61536.raw.1.zip
Processed data (1)E-GEOD-61536.processed.1.zip
Array designA-GEOD-13818.adf.txt
Links