1. Microbiology and Infectious Disease
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Transcriptomic analysis reveals reduced transcriptional activity in the malaria parasite Plasmodium cynomolgi during progression into dormancy

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Cite this article as: eLife 2018;7:e41081 doi: 10.7554/eLife.41081

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.

Article and author information

Author details

  1. Nicole L Bertschi

    Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, Basel, Switzerland
    Competing interests
    Nicole L Bertschi, employed by and/or shareholders of Novartis Pharma AG.
  2. Annemarie Voorberg-van der Wel

    Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9403-0515
  3. Anne-Marie Zeeman

    Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, Netherlands
    Competing interests
    No competing interests declared.
  4. Sven Schuierer

    Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, Basel, Switzerland
    Competing interests
    Sven Schuierer, employed by and/or shareholders of Novartis Pharma AG.
  5. Florian Nigsch

    Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, Basel, Switzerland
    Competing interests
    Florian Nigsch, employed by and/or shareholders of Novartis Pharma AG.
  6. Walter Carbone

    Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, Basel, Switzerland
    Competing interests
    Walter Carbone, employed by and/or shareholders of Novartis Pharma AG.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6150-8295
  7. Judith Knehr

    Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, Basel, Switzerland
    Competing interests
    Judith Knehr, employed by and/or shareholders of Novartis Pharma AG.
  8. Devendra Kumar Gupta

    Novartis Institute for Tropical Diseases, Emeryville, United States
    Competing interests
    Devendra Kumar Gupta, employed by and/or shareholders of Novartis Pharma AG.
  9. Sam O Hofman

    Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, Netherlands
    Competing interests
    No competing interests declared.
  10. Nicole van der Werff

    Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, Netherlands
    Competing interests
    No competing interests declared.
  11. Ivonne Nieuwenhuis

    Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, Netherlands
    Competing interests
    No competing interests declared.
  12. Els Klooster

    Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, Netherlands
    Competing interests
    No competing interests declared.
  13. Bart W Faber

    Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, Netherlands
    Competing interests
    No competing interests declared.
  14. Erika L Flannery

    Novartis Institute for Tropical Diseases, Emeryville, United States
    Competing interests
    Erika L Flannery, employed by and/or shareholders of Novartis Pharma AG.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0665-7954
  15. Sebastian Mikolajczak

    Novartis Institute for Tropical Diseases, Emeryville, United States
    Competing interests
    Sebastian Mikolajczak, employed by and/or shareholders of Novartis Pharma AG.
  16. Binesh Shrestha

    Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, Basel, Switzerland
    Competing interests
    Binesh Shrestha, employed by and/or shareholders of Novartis Pharma AG.
  17. Martin Beibel

    Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, Basel, Switzerland
    Competing interests
    Martin Beibel, employed by and/or shareholders of Novartis Pharma AG.
  18. Tewis Bouwmeester

    Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, Basel, Switzerland
    Competing interests
    Tewis Bouwmeester, employed by and/or shareholders of Novartis Pharma AG.
  19. Niwat Kangwanrangsan

    Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand
    Competing interests
    No competing interests declared.
  20. Jetsumon Sattabongkot

    Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3938-4588
  21. Thierry Tidiane Diagana

    Novartis Institute for Tropical Diseases, Emeryville, United States
    Competing interests
    Thierry Tidiane Diagana, employed by and/or shareholders of Novartis Pharma AG.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8520-5683
  22. Clemens H M Kocken

    Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, Netherlands
    For correspondence
    kocken@bprc.nl
    Competing interests
    No competing interests declared.
  23. Guglielmo Roma

    Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, Basel, Switzerland
    For correspondence
    guglielmo.roma@novartis.com
    Competing interests
    Guglielmo Roma, employed by and shareholders of Novartis Pharma AG.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8020-4219

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

  1. Urszula Krzych, Walter Reed Army Institute of Research, United States

Publication history

  1. Received: August 28, 2018
  2. Accepted: December 23, 2018
  3. Accepted Manuscript published: December 27, 2018 (version 1)

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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