Plasmodium falciparum adapts its investment into replication versus transmission according to the host environment

  1. Abdirahman I Abdi  Is a corresponding author
  2. Fiona Achcar
  3. Lauriane Sollelis
  4. João Luiz Silva-Filho
  5. Kioko Mwikali
  6. Michelle Muthui
  7. Shaban Mwangi
  8. Hannah W Kimingi
  9. Benedict Orindi
  10. Cheryl Andisi
  11. Manon Alkema
  12. Amrita Chandrasekar
  13. Peter C Bull
  14. Philip Bejon
  15. Katarzyna Modrzynska
  16. Teun Bousema
  17. Matthias Marti  Is a corresponding author
  1. KEMRI-Wellcome Trust Research Programme, Kenya
  2. University of Glasgow, United Kingdom
  3. Radboud University Nijmegen Medical Centre, Netherlands

Abstract

The malaria parasite life cycle includes asexual replication in human blood, with a proportion of parasites differentiating to gametocytes required for transmission to mosquitoes. Commitment to differentiate into gametocytes, which is marked by activation of the parasite transcription factor ap2-g, is known to be influenced by host factors but a comprehensive model remains uncertain. Here we analyze data from 828 children in Kilifi, Kenya with severe, uncomplicated, and asymptomatic malaria infection over 18 years of falling malaria transmission. We examine markers of host immunity and metabolism, and markers of parasite growth and transmission investment. We find that inflammatory responses associated with reduced plasma lysophosphatidylcholine levels are associated with markers of increased investment in parasite sexual reproduction (i.e., transmission investment) and reduced growth (i.e., asexual replication). This association becomes stronger with falling transmission and suggests that parasites can rapidly respond to the within-host environment, which in turn is subject to changing transmission.

Data availability

Raw data and script for all the analyses in this manuscript are available at https://doi.org/10.7910/DVN/BXXVRY. mzML mass spectrometry files are available at MetaboLights at https://www.ebi.ac.uk/metabolights/editor/study/MTBLS5130

The following data sets were generated

Article and author information

Author details

  1. Abdirahman I Abdi

    Biosciences, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
    For correspondence
    aabdi@kemri-wellcome.org
    Competing interests
    The authors declare that no competing interests exist.
  2. Fiona Achcar

    Wellcome Center for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8792-7615
  3. Lauriane Sollelis

    Wellcome Center for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. João Luiz Silva-Filho

    Wellcome Center for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4762-2205
  5. Kioko Mwikali

    Biosciences, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  6. Michelle Muthui

    Biosciences, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  7. Shaban Mwangi

    Biosciences, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1961-3205
  8. Hannah W Kimingi

    Biosciences, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  9. Benedict Orindi

    Biosciences, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  10. Cheryl Andisi

    Biosciences, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  11. Manon Alkema

    Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8906-0047
  12. Amrita Chandrasekar

    Wellcome Center for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  13. Peter C Bull

    Biosciences, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  14. Philip Bejon

    Pathogen Vector Host Biology, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  15. Katarzyna Modrzynska

    Wellcome Center for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  16. Teun Bousema

    Radboud Institute for Health Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2666-094X
  17. Matthias Marti

    Wellcome Centre for Molecular Parasitology, University of Glasgow, Glasgow, United Kingdom
    For correspondence
    matthias.marti@glasgow.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1040-9566

Funding

Wellcome Trust (110166)

  • Fiona Achcar
  • Lauriane Sollelis
  • João Luiz Silva-Filho
  • Matthias Marti

Wellcome Trust (104111)

  • Fiona Achcar
  • Lauriane Sollelis
  • João Luiz Silva-Filho
  • Matthias Marti

Royal Society (Wolfson Merit Award)

  • Matthias Marti

European Research Council

  • Teun Bousema

Wellcome Trust (209289/Z/17/Z)

  • Abdirahman I Abdi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Ethical approval was granted by the Scientific Ethics Review Unit of the Kenya Medical Research Institute under the protocol; KEMRI/SERU/3149, and informed consent was obtained from the parents/guardian of the children.

Reviewing Editor

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

Publication history

  1. Received: November 24, 2022
  2. Accepted: March 1, 2023
  3. Accepted Manuscript published: March 14, 2023 (version 1)

Copyright

© 2023, Abdi 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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  1. Abdirahman I Abdi
  2. Fiona Achcar
  3. Lauriane Sollelis
  4. João Luiz Silva-Filho
  5. Kioko Mwikali
  6. Michelle Muthui
  7. Shaban Mwangi
  8. Hannah W Kimingi
  9. Benedict Orindi
  10. Cheryl Andisi
  11. Manon Alkema
  12. Amrita Chandrasekar
  13. Peter C Bull
  14. Philip Bejon
  15. Katarzyna Modrzynska
  16. Teun Bousema
  17. Matthias Marti
(2023)
Plasmodium falciparum adapts its investment into replication versus transmission according to the host environment
eLife 12:e85140.
https://doi.org/10.7554/eLife.85140

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