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Trypanosoma brucei cattle infections contain cryptic transmission‑adapted bloodstream forms at low parasitaemia

Lookup NU author(s): Dr Emma BriggsORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Tsetse‑transmitted Trypanosoma parasites infect a wide host range and cause both Human African Trypanosomiasis and Animal African Trypanosomosis. In rodent infections, T. brucei transitions from proliferative slender to tsetse‑transmissible stumpy forms only at high parasitaemia via a density‑dependent quorum‑sensing mechanism. However, chronic bovine infections occur at much lower parasitaemia, below the densities assumed to trigger differentiation. Using scRNA‑seq and microscopy, this study identifies mixed slender‑ and stumpy‑associated transcriptomes in cattle blood despite low parasitaemia, along with reduced division and shortened flagella indicative of differentiation. Comparisons with murine infections and in vitro culture reveal conserved slender/stumpy transcriptomic signatures with host‑specific differences, suggesting cryptic differentiation and challenging long‑standing assumptions about stumpy formation in natural hosts.


Publication metadata

Author(s): Larcombe SD, Paxton E, Vrettou C, Steketee PC, Matthews KR, Morrison LJ, Briggs EM

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2025

Volume: 16

Online publication date: 05/11/2025

Acceptance date: 25/09/2025

Date deposited: 08/04/2026

ISSN (electronic): 2041-1723

Publisher: Springer Nature

URL: https://doi.org/10.1038/s41467-025-64750-y

DOI: 10.1038/s41467-025-64750-y

Data Access Statement: The scRNA-seq data generated in this study have been deposited in the European Nucleotide Archive database under accession code PRJEB66078. The processed scRNA-seq data are available at zenodo.org under https://doi.org/10.5281/zenodo.14515536. All other data generated in this study are provided in the Supplementary Information/Source data file. The in vitro and mouse derived scRNA-seq data used in this study are available in the European Nucleotide Archive database under accession codes PRJEB41744 and PRJEB60851, respectively, and as processed data at zenodo.org under https://doi.org/10.5281/zenodo.14515536 Source data are provided with this paper.

PubMed id: 41193429


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Funding

Funder referenceFunder name
BBSRC Discovery Fellowship (BB/X009807/1)
MRC Career Development Award (MR/Z504786/1)
Roslin Institute Pump Priming BBSRC grant (sub-award from BBS/E/RL/230002C)
Sir Henry Wellcome Fellowship (218648/Z/19/Z)
Wellcome Trust collaborative award (206815/Z/17/Z)
Wellcome Trust Investigator award (221717/Z/20/Z)
United Kingdom Biotechnology and Biological Sciences Research Council (BBS/E/RL/230002C)

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