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

• DOI: 10.7554/elife.41081
• Publication Date: 2018-12-27T13:00:16Z
• Authors: Nicole L Bertschi; Annemarie Voorber...; Anne-Marie Zeeman; Sven Schuierer; Florian Nigsch; Walter Carbone; Judith Knehr; Devendra K Gupta; Sam O Hofman; Nicole van der Werff; Ivonne Nieuwenhuis; Els Klooster; Bart W Faber; Erika L Flannery; Sebastian A Mikol...; Vorada Chuenchob; Binesh Shrestha; Martin Beibel; Tewis Bouwmeester; Niwat Kangwanrangsan; Jetsumon Sattabon...; Thierry T Diagana; Clemens HM Kocken; Guglielmo Roma
• Keywords: Primates; Microbiology and Infectious Disease; 0303 health sciences; Time Factors; maturation; QH301-705.5; Science; Gene Expression Profiling; Q; malaria; R; 3. Good health; transcriptomics; 03 medical and health sciences; hypnozoites; plasmodium; Liver; Medicine; Animals; Biology (General); liver stages; Plasmodium cynomolgi

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.