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Plasmodium parasites mount an arrest response to dihydroartemisinin, as revealed by whole transcriptome shotgun sequencing (RNA-seq) and microarray study

BACKGROUND: Control of malaria is threatened by emerging parasite resistance to artemisinin and derivative drug (ART) therapies. The molecular detail of how Plasmodium malaria parasites respond to ART and how this could contribute to resistance are not well understood. To address this question, we p...

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Autores principales: Shaw, Philip J., Chaotheing, Sastra, Kaewprommal, Pavita, Piriyapongsa, Jittima, Wongsombat, Chayaphat, Suwannakitti, Nattida, Koonyosying, Pongpisid, Uthaipibull, Chairat, Yuthavong, Yongyuth, Kamchonwongpaisan, Sumalee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618149/
https://www.ncbi.nlm.nih.gov/pubmed/26490244
http://dx.doi.org/10.1186/s12864-015-2040-0
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author Shaw, Philip J.
Chaotheing, Sastra
Kaewprommal, Pavita
Piriyapongsa, Jittima
Wongsombat, Chayaphat
Suwannakitti, Nattida
Koonyosying, Pongpisid
Uthaipibull, Chairat
Yuthavong, Yongyuth
Kamchonwongpaisan, Sumalee
author_facet Shaw, Philip J.
Chaotheing, Sastra
Kaewprommal, Pavita
Piriyapongsa, Jittima
Wongsombat, Chayaphat
Suwannakitti, Nattida
Koonyosying, Pongpisid
Uthaipibull, Chairat
Yuthavong, Yongyuth
Kamchonwongpaisan, Sumalee
author_sort Shaw, Philip J.
collection PubMed
description BACKGROUND: Control of malaria is threatened by emerging parasite resistance to artemisinin and derivative drug (ART) therapies. The molecular detail of how Plasmodium malaria parasites respond to ART and how this could contribute to resistance are not well understood. To address this question, we performed a transcriptomic study of dihydroartemisinin (DHA) response in P. falciparum K1 strain and in P. berghei ANKA strain using microarray and RNA-seq technology. RESULTS: Microarray data from DHA-treated P. falciparum trophozoite stage parasites revealed a response pattern that is overall less trophozoite-like and more like the other stages of asexual development. A meta-analysis of these data with previously published data from other ART treatments revealed a set of common differentially expressed genes. Notably, ribosomal protein genes are down-regulated in response to ART. A similar pattern of trophozoite transcriptomic change was observed from RNA-seq data. 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. No genes are differentially expressed in DHA-treated P. falciparum schizonts. The transcriptional response of P. berghei to DHA treatment in vivo in infected mice is similar to the P. falciparum in vitro culture ring and trophozoite responses, in which ribosomal protein genes are notably down-regulated. CONCLUSIONS: Ring and trophozoite stage Plasmodium respond to ART by arresting metabolic processes such as protein synthesis and glycolysis. This response can be protective in rings, as shown by the phenomenon of dormancy. In contrast, this response is not as protective in trophozoites owing to their commitment to a highly active and vulnerable metabolic state. The lower metabolic demands of schizonts could explain why they are less sensitive and unresponsive to ART. The ART response pattern is revealed clearly from RNA-seq data, suggesting that this technology is of great utility for studying drug response in Plasmodium. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2040-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-46181492015-10-25 Plasmodium parasites mount an arrest response to dihydroartemisinin, as revealed by whole transcriptome shotgun sequencing (RNA-seq) and microarray study Shaw, Philip J. Chaotheing, Sastra Kaewprommal, Pavita Piriyapongsa, Jittima Wongsombat, Chayaphat Suwannakitti, Nattida Koonyosying, Pongpisid Uthaipibull, Chairat Yuthavong, Yongyuth Kamchonwongpaisan, Sumalee BMC Genomics Research Article BACKGROUND: Control of malaria is threatened by emerging parasite resistance to artemisinin and derivative drug (ART) therapies. The molecular detail of how Plasmodium malaria parasites respond to ART and how this could contribute to resistance are not well understood. To address this question, we performed a transcriptomic study of dihydroartemisinin (DHA) response in P. falciparum K1 strain and in P. berghei ANKA strain using microarray and RNA-seq technology. RESULTS: Microarray data from DHA-treated P. falciparum trophozoite stage parasites revealed a response pattern that is overall less trophozoite-like and more like the other stages of asexual development. A meta-analysis of these data with previously published data from other ART treatments revealed a set of common differentially expressed genes. Notably, ribosomal protein genes are down-regulated in response to ART. A similar pattern of trophozoite transcriptomic change was observed from RNA-seq data. 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. No genes are differentially expressed in DHA-treated P. falciparum schizonts. The transcriptional response of P. berghei to DHA treatment in vivo in infected mice is similar to the P. falciparum in vitro culture ring and trophozoite responses, in which ribosomal protein genes are notably down-regulated. CONCLUSIONS: Ring and trophozoite stage Plasmodium respond to ART by arresting metabolic processes such as protein synthesis and glycolysis. This response can be protective in rings, as shown by the phenomenon of dormancy. In contrast, this response is not as protective in trophozoites owing to their commitment to a highly active and vulnerable metabolic state. The lower metabolic demands of schizonts could explain why they are less sensitive and unresponsive to ART. The ART response pattern is revealed clearly from RNA-seq data, suggesting that this technology is of great utility for studying drug response in Plasmodium. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2040-0) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-21 /pmc/articles/PMC4618149/ /pubmed/26490244 http://dx.doi.org/10.1186/s12864-015-2040-0 Text en © Shaw et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Shaw, Philip J.
Chaotheing, Sastra
Kaewprommal, Pavita
Piriyapongsa, Jittima
Wongsombat, Chayaphat
Suwannakitti, Nattida
Koonyosying, Pongpisid
Uthaipibull, Chairat
Yuthavong, Yongyuth
Kamchonwongpaisan, Sumalee
Plasmodium parasites mount an arrest response to dihydroartemisinin, as revealed by whole transcriptome shotgun sequencing (RNA-seq) and microarray study
title Plasmodium parasites mount an arrest response to dihydroartemisinin, as revealed by whole transcriptome shotgun sequencing (RNA-seq) and microarray study
title_full Plasmodium parasites mount an arrest response to dihydroartemisinin, as revealed by whole transcriptome shotgun sequencing (RNA-seq) and microarray study
title_fullStr Plasmodium parasites mount an arrest response to dihydroartemisinin, as revealed by whole transcriptome shotgun sequencing (RNA-seq) and microarray study
title_full_unstemmed Plasmodium parasites mount an arrest response to dihydroartemisinin, as revealed by whole transcriptome shotgun sequencing (RNA-seq) and microarray study
title_short Plasmodium parasites mount an arrest response to dihydroartemisinin, as revealed by whole transcriptome shotgun sequencing (RNA-seq) and microarray study
title_sort plasmodium parasites mount an arrest response to dihydroartemisinin, as revealed by whole transcriptome shotgun sequencing (rna-seq) and microarray study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618149/
https://www.ncbi.nlm.nih.gov/pubmed/26490244
http://dx.doi.org/10.1186/s12864-015-2040-0
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