Transcriptomic analysis reveals reduced transcriptional activity in the malaria parasite Plasmodium cynomolgi during progression into dormancy
- Novartis Institutes for BioMedical Research, Switzerland
- Biomedical Primate Research Centre, Netherlands
- Novartis Institute for Tropical Diseases, United States
- Mahidol University, Thailand
Abstract
Relapses of Plasmodium dormant liver hypnozoites compromise malaria eradication efforts. New radical cure drugs are urgently needed, yet the vast gap in knowledge of hypnozoite biology impedes drug discovery. We previously unraveled the transcriptome of 6 to 7 day-old P. cynomolgi liver stages, highlighting pathways associated with hypnozoite dormancy (Voorberg-van der Wel, 2017). We now extend these findings by transcriptome profiling of 9 to 10 day-old liver stage parasites, thus revealing for the first time the maturation of the dormant stage over time. Although progression of dormancy leads to a 10-fold decrease in transcription and expression of only 840 genes, including genes associated with housekeeping functions, we show that pathways involved in quiescence, energy metabolism and maintenance of genome integrity remain the prevalent pathways active in mature hypnozoites.
Data availability
The raw RNA-sequencing reads are available in the NCBI Short Read Archive (https://www.ncbi.nlm.nih.gov/sra) under accession number SRP096160.
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Malaria Liver Stages Transcriptome, '18NCBI Short Read Archive, SRP096160.
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Malaria Liver Stages Transcriptome, '17NCBI Short Read Archive, SRP096160.
Article and author information
Author details
Annemarie Voorberg-van der Wel
Jetsumon Sattabongkot
Thierry Tidiane Diagana
Funding
Bill and Melinda Gates Foundation
- Thierry Tidiane Diagana
- Clemens H M Kocken
- Guglielmo Roma
Wellcome
- Thierry Tidiane Diagana
- Clemens H M Kocken
Medicines for Malaria Venture
- Thierry Tidiane Diagana
- Clemens H M Kocken
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Nonhuman primates were used because no other models (in vitro or in vivo) were suitable for the aims of this project. The research protocol was approved by the local independent ethical committee conform Dutch law (BPRC Dier Experimenten Commissie, DEC, agreement number #708). Details are described by Voorberg-van der Wel [4].
Reviewing Editor
- Urszula Krzych, Walter Reed Army Institute of Research, United States
Publication history
- Received: August 28, 2018
- Accepted: December 23, 2018
- Accepted Manuscript published: December 27, 2018 (version 1)
- Version of Record published: January 23, 2019 (version 2)
Copyright
© 2018, Bertschi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Transcriptomic analysis reveals reduced transcriptional activity in the malaria parasite Plasmodium cynomolgi during progression into dormancy
eLife 7:e41081.
https://doi.org/10.7554/eLife.41081
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