1. Microbiology and Infectious Disease

Unexpected plasticity in the life cycle of Trypanosoma brucei

  1. Sarah Schuster
  2. Jaime Lisack
  3. Ines Subota
  4. Henriette Zimmermann
  5. Christian Reuter
  6. Tobias Mueller
  7. Brooke Morriswood
  8. Markus Engstler  Is a corresponding author
  1. University of Würzburg, Germany
  2. University of Wuerzburg, Germany
https://doi.org/10.7554/eLife.66028
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Cite this article
  1. Sarah Schuster
  2. Jaime Lisack
  3. Ines Subota
  4. Henriette Zimmermann
  5. Christian Reuter
  6. Tobias Mueller
  7. Brooke Morriswood
  8. Markus Engstler
(2021)
Unexpected plasticity in the life cycle of Trypanosoma brucei
eLife 10:e66028.
https://doi.org/10.7554/eLife.66028
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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.

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All original data are in the submission

Article and author information

Author details

  1. Sarah Schuster

    Department of Cell and Developmental Biology, University of Würzburg, Würzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  2. Jaime Lisack

    Department of Cell and Developmental Biology, University of Würzburg, Würzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  3. Ines Subota

    Department of Cell and Developmental Biology, University of Würzburg, Würzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  4. Henriette Zimmermann

    Department of Cell and Developmental Biology, University of Würzburg, Würzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  5. Christian Reuter

    Department of Cell and Developmental Biology, University of Würzburg, Würzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  6. Tobias Mueller

    University of Wuerzburg, Wuerzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.

  7. Brooke Morriswood

    University of Wuerzburg, Wuerzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7031-3801

  8. Markus Engstler

    Department of Cell and Developmental Biology, University of Würzburg, Würzburg, Germany
    For correspondence
    markus.engstler@biozentrum.uni-wuerzburg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1436-5759

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

  1. Christine Clayton, DKFZ-ZMBH Alliance, Germany

Version history

  1. Preprint posted: July 29, 2019 (view preprint)
  2. Received: December 22, 2020
  3. Accepted: August 5, 2021
  4. Accepted Manuscript published: August 6, 2021 (version 1)
  5. Version of Record published: September 17, 2021 (version 2)
  6. 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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  1. Sarah Schuster
  2. Jaime Lisack
  3. Ines Subota
  4. Henriette Zimmermann
  5. Christian Reuter
  6. Tobias Mueller
  7. Brooke Morriswood
  8. Markus Engstler
(2021)
Unexpected plasticity in the life cycle of Trypanosoma brucei
eLife 10:e66028.
https://doi.org/10.7554/eLife.66028

Share this article

https://doi.org/10.7554/eLife.66028

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Further reading

    1. Microbiology and Infectious Disease

    Comment on ‘Unexpected plasticity in the life cycle of Trypanosoma brucei’

    Keith R Matthews, Stephen Larcombe
    Scientific Correspondence

    Schuster et al. make the important observation that small numbers of trypanosomes can infect tsetse flies, and further argue that this can occur whether the infecting parasites are developmentally ‘slender’ or ‘stumpy’(Schuster et al., 2021). We welcome their careful experiments but disagree that they require a rethink of the trypanosome life-cycle. Instead, the study reveals that stumpy forms are more likely to successfully infect flies, the key limit on parasite transmission, and we predict this advantage would be greatly amplified in tsetse infections in the field. Further, we argue that stumpy forms are defined by a suite of molecular adaptations for life-cycle progression, with morphology being a secondary feature. Finally, their dominance in chronic infections means most natural tsetse infections would involve stumpy forms, even in small numbers. Our interpretation does not require re-evaluation of the obligatory life cycle of the parasite, where stumpy forms are selected to sustain transmission.

    1. Microbiology and Infectious Disease

    Parasite Transmission: A two-stage solution

    Fabien Guegan, Luisa Figueiredo
    Insight

    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.

    1. Microbiology and Infectious Disease
    2. Structural Biology and Molecular Biophysics

    Molecular mechanism of complement inhibition by the trypanosome receptor ISG65

    Alexander D Cook, Mark Carrington, Matthew K Higgins
    Research Article

    African trypanosomes replicate within infected mammals where they are exposed to the complement system. This system centres around complement C3, which is present in a soluble form in serum but becomes covalently deposited onto the surfaces of pathogens after proteolytic cleavage to C3b. Membrane-associated C3b triggers different complement-mediated effectors which promote pathogen clearance. To counter complement-mediated clearance, African trypanosomes have a cell surface receptor, ISG65, which binds to C3b and which decreases the rate of trypanosome clearance in an infection model. However, the mechanism by which ISG65 reduces C3b function has not been determined. We reveal through cryogenic electron microscopy that ISG65 has two distinct binding sites for C3b, only one of which is available in C3 and C3d. We show that ISG65 does not block the formation of C3b or the function of the C3 convertase which catalyses the surface deposition of C3b. However, we show that ISG65 forms a specific conjugate with C3b, perhaps acting as a decoy. ISG65 also occludes the binding sites for complement receptors 2 and 3, which may disrupt recruitment of immune cells, including B cells, phagocytes, and granulocytes. This suggests that ISG65 protects trypanosomes by combining multiple approaches to dampen the complement cascade.