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

Autor: Bertschi NL; Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Europe., Voorberg-van der Wel A; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Zeeman AM; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Schuierer S; Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Europe., Nigsch F; Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Europe., Carbone W; Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Europe., Knehr J; Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Europe., Gupta DK; Novartis Institute for Tropical Diseases, Novartis Pharma AG, Emeryville, United States., Hofman SO; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., van der Werff N; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Nieuwenhuis I; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Klooster E; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Faber BW; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Flannery EL; Novartis Institute for Tropical Diseases, Novartis Pharma AG, Emeryville, United States., Mikolajczak SA; Novartis Institute for Tropical Diseases, Novartis Pharma AG, Emeryville, United States., Chuenchob V; Novartis Institute for Tropical Diseases, Novartis Pharma AG, Emeryville, United States., Shrestha B; Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Europe., Beibel M; Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Europe., Bouwmeester T; Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Europe., Kangwanrangsan N; Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand., Sattabongkot J; Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Diagana TT; Novartis Institute for Tropical Diseases, Novartis Pharma AG, Emeryville, United States., Kocken CH; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Roma G; Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Europe.
Jazyk: angličtina
Zdroj: ELife [Elife] 2018 Dec 27; Vol. 7. Date of Electronic Publication: 2018 Dec 27.
DOI: 10.7554/eLife.41081
Abstrakt: 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.
Competing Interests: NB, SS, FN, WC, JK, DG, EF, SM, VC, BS, MB, TB, TD, GR Employed by and/or shareholder of Novartis Pharma AG. AV, AZ, SH, Nv, IN, EK, BF, NK, JS, CK No competing interests declared
(© 2018, Bertschi et al.)
Databáze: MEDLINE