Projects per year
Abstract
The development of Trypanosoma brucei in its mammalian host is marked by a dis-tinct 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.
Original language | English |
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Article number | e2306848120 |
Number of pages | 9 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 120 |
Issue number | 42 |
Early online date | 12 Oct 2023 |
DOIs | |
Publication status | Published - 17 Oct 2023 |
Keywords / Materials (for Non-textual outputs)
- parasite
- Trypanosoma brucei
- differentiation
- single cell
- commitment
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Deciphering developmental commitment in African trypanosomes using single-cell transcriptomics
Briggs, E.
20/01/20 → 19/01/24
Project: Research
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Challenging trypanosome antigenic variation paradigms using natural systems
2/04/18 → 2/04/23
Project: Research