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Updated: Jan 31, 2026
Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
Published on: November 22, 2024
Transcriptomic analysis reveals reduced transcriptional activity in the malaria parasite Plasmodium cynomolgi during
Nicole L Bertschi1, Annemarie Voorberg-van der Wel2, Anne-Marie Zeeman2
1Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Europe.
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 et al., 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.
Insights
Understanding Plasmodium hypnozoite maturation is key to developing new malaria treatments. This study reveals dormant stage progression involves reduced transcription but sustained pathways for quiescence and genome integrity.
Area of Science:
- Malariology
- Molecular Biology
- Parasitology
Background:
- Relapses from Plasmodium dormant liver hypnozoites hinder malaria eradication.
- Knowledge of hypnozoite biology is limited, impeding the development of radical cure drugs.
- Previous work characterized early P. cynomolgi liver stage transcriptomes.
Purpose of the Study:
- To profile the transcriptome of later-stage P. cynomolgi liver hypnozoites (9-10 days old).
- To understand the temporal changes in gene expression during hypnozoite maturation.
- To identify key pathways active in mature dormant liver stages.
Main Methods:
- Transcriptome profiling of P. cynomolgi liver stage parasites at 9-10 days post-infection.
- Comparative analysis with previously published data from 6-7 day-old parasites.
- Bioinformatic analysis to identify active gene pathways.
Main Results:
- Hypnozoite maturation over time showed a 10-fold decrease in overall transcription.
- Only 840 genes remained expressed in mature hypnozoites, including housekeeping genes.
- Active pathways in mature hypnozoites are associated with quiescence, energy metabolism, and genome integrity.
Conclusions:
- The maturation of Plasmodium hypnozoites involves significant transcriptional downregulation.
- Despite reduced gene expression, essential pathways for survival and integrity are maintained.
- These findings provide crucial insights for developing novel anti-malarial drugs targeting dormant stages.
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