Unexpected plasticity in the life cycle of Trypanosoma brucei
- University of Würzburg, Germany
- University of Wuerzburg, Germany
Abstract
African trypanosomes cause sleeping sickness in humans and nagana in cattle. These unicellular parasites are transmitted by the bloodsucking tsetse fly. In the mammalian host's circulation, proliferating slender stage cells differentiate into cell cycle-arrested stumpy stage cells when they reach high population densities. This stage transition is thought to fulfil two main functions: first, it auto-regulates the parasite load in the host; second, the stumpy stage is regarded as the only stage capable of successful vector transmission. Here, we show that proliferating slender stage trypanosomes express the mRNA and protein of a known stumpy stage marker, complete the complex life cycle in the fly as successfully as the stumpy stage, and require only a single parasite for productive infection. These findings suggest a reassessment of the traditional view of the trypanosome life cycle. They may also provide a solution to a long-lasting paradox, namely the successful transmission of parasites in chronic infections, despite low parasitemia.
Data availability
All original data are in the submission
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (EN305)
- Markus Engstler
Deutsche Forschungsgemeinschaft (SPP1726)
- Markus Engstler
German-Israeli Foundation for Scientific Research and Development (ant I-473-416.13/2018)
- Markus Engstler
Deutsche Forschungsgemeinschaft (GRK2157)
- Markus Engstler
Deutsche Forschungsgemeinschaft (396187369)
- Brooke Morriswood
Bundesministerium für Bildung und Forschung (NUM Organostrat)
- Markus Engstler
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Christine Clayton, DKFZ-ZMBH Alliance, Germany
Version history
- Preprint posted: July 29, 2019 (view preprint)
- Received: December 22, 2020
- Accepted: August 5, 2021
- Accepted Manuscript published: August 6, 2021 (version 1)
- Version of Record published: September 17, 2021 (version 2)
- Version of Record updated: January 31, 2022 (version 3)
Copyright
© 2021, Schuster et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Unexpected plasticity in the life cycle of Trypanosoma brucei
eLife 10:e66028.
https://doi.org/10.7554/eLife.66028
Further reading
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- Microbiology and Infectious Disease
The parasite that causes African sleeping sickness can be transmitted from mammals to tsetse flies in two stages of its lifecycle, rather than one as was previously thought.
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- Microbiology and Infectious Disease
- Structural Biology and Molecular Biophysics
Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we examine the impact of mutations across the spectrum of viable amino acid sequences on the biophysical phenotypes of the highly expressed and multifunctional nucleocapsid protein. We find variation in the physicochemical parameters of its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur in related coronaviruses. In biophysical experiments with several N-protein species carrying mutations associated with major variants, we find that point mutations in the IDRs can have nonlocal impact and modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, and liquid-liquid phase separation. In the Omicron variant, distant mutations in different IDRs have compensatory effects in shifting a delicate balance of interactions controlling protein assembly properties, and include the creation of a new protein-protein interaction interface in the N-terminal IDR through the defining P13L mutation. A picture emerges where genetic diversity is accompanied by significant variation in biophysical characteristics of functional N-protein species, in particular in the IDRs.
