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Lookup NU author(s): Dr Emma BriggsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
The development of Trypanosoma brucei in its mammalian host is marked by a distinct morphological change as replicative "slender" forms differentiate into cell cycle arrested "stumpy" forms in a quorum-sensing-dependent manner. Although stumpy forms dominate chronic infections at the population level, the proportion of replicative parasites at the individual cell level and the irreversibility of arrest in the bloodstream are unclear. Here, we experimentally demonstrate that developmental cell cycle arrest is definitively irreversible in acute and chronic infections in mice. Furthermore, analysis of replicative capacity and single-cell transcriptome profiling reveal a temporal hierarchy, whereby cell cycle arrest and appearance of a reversible stumpy-like transcriptome precede irreversible commitment and morphological change. Unexpectedly, we show that proliferating parasites are exceptionally scarce in the blood after infections are established. This challenges the ability of bloodstream trypanosomes to sustain infection by proliferation or antigenic variation, these parasites instead being overwhelmingly adapted for transmission.
Author(s): Larcombe SD, Briggs EM, Savill N, Szoor B, Matthews KR
Publication type: Article
Publication status: Published
Journal: Proceedings of the National Academy of Sciences of the United States of America
Year: 2023
Volume: 120
Issue: 42
Print publication date: 17/10/2023
Online publication date: 12/10/2023
Acceptance date: 30/08/2023
Date deposited: 29/01/2025
ISSN (print): 0027-8424
ISSN (electronic): 1091-6490
Publisher: National Academy of Sciences
URL: https://doi.org/10.1073/pnas.2306848120
DOI: 10.1073/pnas.2306848120
Data Access Statement: For scRNAseq data, the raw fastq is registered with the ENA (European Nucleotide Archive) (https://www.ebi.ac.uk/ ena/browser/home) under the study reference PRJEB60851 (https://www.ebi. ac.uk/ena/browser/view/PRJEB60851) (53). The original code is available at https://tinyurl.com/28ydamyy (52)
PubMed id: 37824530
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