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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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.

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

    Telomerase RNA component knockout exacerbates Staphylococcus aureus pneumonia by extensive inflammation and dysfunction of T cells

    Yasmina Reisser, Franziska Hornung ... Stefanie Deinhardt-Emmer
    Research Article

    The telomerase RNA component (Terc) constitutes a non-coding RNA critical for telomerase function, commonly associated with aging and pivotal in immunomodulation during inflammation. Our study unveils heightened susceptibility to pneumonia caused by Staphylococcus aureus (S. aureus) in Terc knockout (Tercko/ko) mice compared to both young and old infected counterparts. The exacerbated infection in Tercko/ko mice correlates with heightened inflammation, manifested by elevated interleukin-1β (IL-1β) levels and activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome within the lung. Employing mRNA sequencing methods alongside in vitro analysis of alveolar macrophages (AMs) and T cells, our study elucidates a compelling correlation between Tercko/ko, inflammation, and impaired T cell functionality. Terc deletion results in compromised T cell function, characterized by dysregulation of the T cell receptor and absence of CD247, potentially compromising the host’s capacity to mount an effective immune response against S. aureus. This investigation provides insights into the intricate mechanisms governing increased vulnerability to severe pneumonia in the context of Terc deficiency, which might also contribute to aging-related pathologies, while also highlighting the influence of Terc on T cell function.