Transcriptomic analysis reveals reduced transcriptional activity in the malaria parasite Plasmodium cynomolgi during progression into dormancy

Author:

Bertschi Nicole L1,Voorberg-van der Wel Annemarie2ORCID,Zeeman Anne-Marie2,Schuierer Sven1,Nigsch Florian1,Carbone Walter1ORCID,Knehr Judith1,Gupta Devendra K3,Hofman Sam O2,van der Werff Nicole2,Nieuwenhuis Ivonne2,Klooster Els2,Faber Bart W2,Flannery Erika L3ORCID,Mikolajczak Sebastian A3,Chuenchob Vorada3,Shrestha Binesh1,Beibel Martin1,Bouwmeester Tewis1,Kangwanrangsan Niwat4,Sattabongkot Jetsumon5ORCID,Diagana Thierry T3ORCID,Kocken Clemens HM2,Roma Guglielmo1ORCID

Affiliation:

1. Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Europe

2. Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands

3. Novartis Institute for Tropical Diseases, Novartis Pharma AG, Emeryville, United States

4. Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand

5. Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, 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 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.

Funder

Bill and Melinda Gates Foundation

Wellcome

Medicines for Malaria Venture

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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