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

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.

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.

Metrics

  • 2,282
    views
  • 427
    downloads
  • 20
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Share this article

https://doi.org/10.7554/eLife.85140

Further reading

    1. Microbiology and Infectious Disease
    McKenna Harpring, Junghoon Lee ... John V Cox
    Research Article

    Chlamydia trachomatis serovar L2 (Ct), an obligate intracellular bacterium that does not encode FtsZ, divides by a polarized budding process. In the absence of FtsZ, we show that FtsK, a chromosomal translocase, is critical for divisome assembly in Ct. Chlamydial FtsK forms discrete foci at the septum and at the base of the progenitor mother cell, and our data indicate that FtsK foci at the base of the mother cell mark the location of nascent divisome complexes that form at the site where a daughter cell will emerge in the next round of division. The divisome in Ct has a hybrid composition, containing elements of the divisome and elongasome from other bacteria, and FtsK is recruited to nascent divisomes prior to the other chlamydial divisome proteins assayed, including the PBP2 and PBP3 transpeptidases, and MreB and MreC. Knocking down FtsK prevents divisome assembly in Ct and inhibits cell division and septal peptidoglycan synthesis. We further show that MreB does not function like FtsZ and serve as a scaffold for the assembly of the Ct divisome. Rather, MreB is one of the last proteins recruited to the chlamydial divisome, and it is necessary for the formation of septal peptidoglycan rings. Our studies illustrate the critical role of chlamydial FtsK in coordinating divisome assembly and peptidoglycan synthesis in this obligate intracellular bacterial pathogen.

    1. Microbiology and Infectious Disease
    Tao Tang, Weiming Zhong ... Zhipeng Gao
    Research Article

    Saprolegnia parasitica is one of the most virulent oomycete species in freshwater aquatic environments, causing severe saprolegniasis and leading to significant economic losses in the aquaculture industry. Thus far, the prevention and control of saprolegniasis face a shortage of medications. Linalool, a natural antibiotic alternative found in various essential oils, exhibits promising antimicrobial activity against a wide range of pathogens. In this study, the specific role of linalool in protecting S. parasitica infection at both in vitro and in vivo levels was investigated. Linalool showed multifaceted anti-oomycetes potential by both of antimicrobial efficacy and immunomodulatory efficacy. For in vitro test, linalool exhibited strong anti-oomycetes activity and mode of action included: (1) Linalool disrupted the cell membrane of the mycelium, causing the intracellular components leak out; (2) Linalool prohibited ribosome function, thereby inhibiting protein synthesis and ultimately affecting mycelium growth. Surprisingly, meanwhile we found the potential immune protective mechanism of linalool in the in vivo test: (1) Linalool enhanced the complement and coagulation system which in turn activated host immune defense and lysate S. parasitica cells; (2) Linalool promoted wound healing, tissue repair, and phagocytosis to cope with S. parasitica infection; (3) Linalool positively modulated the immune response by increasing the abundance of beneficial Actinobacteriota; (4) Linalool stimulated the production of inflammatory cytokines and chemokines to lyse S. parasitica cells. In all, our findings showed that linalool possessed multifaceted anti-oomycetes potential which would be a promising natural antibiotic alternative to cope with S. parasitica infection in the aquaculture industry.