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Slow growing behavior in African trypanosomes during adipose tissue colonization

Author

Listed:
  • Sandra Trindade

    (Universidade de Lisboa)

  • Mariana Niz

    (Universidade de Lisboa)

  • Mariana Costa-Sequeira

    (Universidade de Lisboa)

  • Tiago Bizarra-Rebelo

    (Universidade de Lisboa)

  • Fábio Bento

    (Universidade de Lisboa
    Institute of Molecular Biology)

  • Mario Dejung

    (Institute of Molecular Biology)

  • Marta Valido Narciso

    (Universidade de Lisboa)

  • Lara López-Escobar

    (Universidade de Lisboa)

  • João Ferreira

    (Universidade de Lisboa)

  • Falk Butter

    (Institute of Molecular Biology)

  • Frédéric Bringaud

    (Université de Bordeaux, CNRS
    Université de Bordeaux, CNRS)

  • Erida Gjini

    (Instituto Gulbenkian de Ciência
    Universidade de Lisboa)

  • Luisa M. Figueiredo

    (Universidade de Lisboa)

Abstract

When Trypanosoma brucei parasites, the causative agent of sleeping sickness, colonize the adipose tissue, they rewire gene expression. Whether this adaptation affects population behavior and disease treatment remained unknown. By using a mathematical model, we estimate that the population of adipose tissue forms (ATFs) proliferates slower than blood parasites. Analysis of the ATFs proteome, measurement of protein synthesis and proliferation rates confirm that the ATFs divide on average every 12 h, instead of 6 h in the blood. Importantly, the population of ATFs is heterogeneous with parasites doubling times ranging between 5 h and 35 h. Slow-proliferating parasites remain capable of reverting to the fast proliferation profile in blood conditions. Intravital imaging shows that ATFs are refractory to drug treatment. We propose that in adipose tissue, a subpopulation of T. brucei parasites acquire a slow growing behavior, which contributes to disease chronicity and treatment failure.

Suggested Citation

  • Sandra Trindade & Mariana Niz & Mariana Costa-Sequeira & Tiago Bizarra-Rebelo & Fábio Bento & Mario Dejung & Marta Valido Narciso & Lara López-Escobar & João Ferreira & Falk Butter & Frédéric Bringaud, 2022. "Slow growing behavior in African trypanosomes during adipose tissue colonization," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34622-w
    DOI: 10.1038/s41467-022-34622-w
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    References listed on IDEAS

    as
    1. David J. Spiegelhalter & Nicola G. Best & Bradley P. Carlin & Angelika Van Der Linde, 2002. "Bayesian measures of model complexity and fit," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 64(4), pages 583-639, October.
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    Cited by:

    1. Christian Reuter & Laura Hauf & Fabian Imdahl & Rituparno Sen & Ehsan Vafadarnejad & Philipp Fey & Tamara Finger & Nicola G. Jones & Heike Walles & Lars Barquist & Antoine-Emmanuel Saliba & Florian Gr, 2023. "Vector-borne Trypanosoma brucei parasites develop in artificial human skin and persist as skin tissue forms," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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