Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1782396889825542144 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4618149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT shawphilipj plasmodiumparasitesmountanarrestresponsetodihydroartemisininasrevealedbywholetranscriptomeshotgunsequencingrnaseqandmicroarraystudy AT chaotheingsastra plasmodiumparasitesmountanarrestresponsetodihydroartemisininasrevealedbywholetranscriptomeshotgunsequencingrnaseqandmicroarraystudy AT kaewprommalpavita plasmodiumparasitesmountanarrestresponsetodihydroartemisininasrevealedbywholetranscriptomeshotgunsequencingrnaseqandmicroarraystudy AT piriyapongsajittima plasmodiumparasitesmountanarrestresponsetodihydroartemisininasrevealedbywholetranscriptomeshotgunsequencingrnaseqandmicroarraystudy AT wongsombatchayaphat plasmodiumparasitesmountanarrestresponsetodihydroartemisininasrevealedbywholetranscriptomeshotgunsequencingrnaseqandmicroarraystudy AT suwannakittinattida plasmodiumparasitesmountanarrestresponsetodihydroartemisininasrevealedbywholetranscriptomeshotgunsequencingrnaseqandmicroarraystudy AT koonyosyingpongpisid plasmodiumparasitesmountanarrestresponsetodihydroartemisininasrevealedbywholetranscriptomeshotgunsequencingrnaseqandmicroarraystudy AT uthaipibullchairat plasmodiumparasitesmountanarrestresponsetodihydroartemisininasrevealedbywholetranscriptomeshotgunsequencingrnaseqandmicroarraystudy AT yuthavongyongyuth plasmodiumparasitesmountanarrestresponsetodihydroartemisininasrevealedbywholetranscriptomeshotgunsequencingrnaseqandmicroarraystudy AT kamchonwongpaisansumalee plasmodiumparasitesmountanarrestresponsetodihydroartemisininasrevealedbywholetranscriptomeshotgunsequencingrnaseqandmicroarraystudy |