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Cited by 5Trypanosoma species research and implicationsResearch on Leishmaniasis StudiesVector-borne infectious diseases

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Mechanisms of life cycle simplification in African trypanosomes

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Oldrieve, Guy R., Venter, Frank, Cayla, Mathieu, Verney, Mylène, Hébert, Laurent, Geerts, Manon, Van Reet, Nick, Matthews, Keith R.·2024·Nature Communications
DOI 10.1038/s41467-024-54555-wPMC PMC11612274

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Abstract

African trypanosomes are important parasites in sub-Saharan Africa that undergo a quorum-sensing dependent development to morphologically ‘stumpy forms’ in mammalian hosts to favour transmission by tsetse flies. However, some trypanosome clades have simplified their lifecycle by escaping dependence on tsetse allowing an expanded geographic range, with direct transmission between hosts achieved via blood-feeding biting flies and vampire bats ( Trypanosoma brucei evansi , causing ‘surra’) or through sexual transmission ( Trypanosoma brucei equiperdum , causing ‘dourine’). Concomitantly, stumpy formation is reduced and the isolates are described as monomorphic, with infections spread widely in Africa, Asia, South America and parts of Europe. Here, using genomic analysis of distinct field isolates, we identify molecular changes that accompany the loss of the stumpy formation in monomorphic clades. Using CRISPR-mediated allelic replacement, mutations in two exemplar genes (Tb927.2.4020; Tb927.5.2580) are confirmed to reduce stumpy formation whereas another (Tb927.11.3400) is implicated in altered motility. Using laboratory selection we identify downregulation of RNA regulators as important in the initial development of monomorphism. This identifies a trajectory of events that simplify the life cycle in emergent and established monomorphic trypanosomes, with impact on disease spread, vector control strategies, geographical range and virulence.

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Metadata

Authors
Oldrieve, G. R., Venter, F., Cayla, M., Verney, M., Hébert, L., Geerts, M., Van Reet, N., & Matthews, K. R.
Affiliations
  • University of Edinburgh (GB)
  • University of York (GB)
  • Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail (FR)
  • Instituut voor Tropische Geneeskunde (BE)
Corresponding author
  • Oldrieve, Guy R.
  • Matthews, Keith R.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-12-02
Volume
15
Issue
1
Pages
10485-10485
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-54555-w
PMC
PMC11612274
OpenAlex
W4404905045
Cited by
5
References
2
Citations by year
2026: 4 · 2025: 1
FWCI
1.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion, cc-by)
  • Lirias (submittedVersion, cc-by)
  • HAL (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (221717/Z/20/Z, 108905/Z/15/Z)
  • RCUK | Medical Research Council (MR/W026996/1)
  • Bill and Melinda Gates Foundation (OPP1174221)
  • Flemish Government EWI SOFI-2018 GIS CENTAURE Recherche Equine and the Regional Council of Normandy
Topics
  • Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
  • Life Sciences › Immunology and Microbiology › Parasitology › Vector-borne infectious diseases
Keywords
African trypanosomes, Trypanosoma brucei, quorum sensing, surra, dourine, tsetse flies, trypanosome motility, parasite virulence, geographic range expansion, vector control
MeSH terms
Animals, Chiroptera, Humans, Life Cycle Stages, Mutation, Trypanosoma brucei brucei, Trypanosomiasis, African, Tsetse Flies, Protozoan Proteins

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