Oldrieve, Guy R, Venter, Frank, Cayla, Mathieu orcid.org/0000-0002-3731-7947 et al. (5 more authors) (2024) Mechanisms of life cycle simplification in African trypanosomes. Nature Communications. 10485. ISSN 2041-1723
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024. The Author(s). |
Keywords: | Life Cycle Stages/genetics,Animals,Trypanosoma brucei brucei/genetics,Trypanosomiasis, African/transmission,Tsetse Flies/parasitology,Protozoan Proteins/genetics,Mutation,Humans,Chiroptera/parasitology |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 10 Dec 2024 16:10 |
Last Modified: | 22 Jan 2025 00:25 |
Published Version: | https://doi.org/10.1038/s41467-024-54555-w |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41467-024-54555-w |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:220678 |