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In vitro maturation of Toxoplasma gondii bradyzoites in human myotubes and their metabolomic characterization

Author

Listed:
  • Céline Christiansen

    (Robert Koch-Institute)

  • Deborah Maus

    (Robert Koch-Institute)

  • Ellen Hoppenz

    (Robert Koch-Institute)

  • Mateo Murillo-León

    (Medical Center University of Freiburg
    University of Freiburg
    University of Freiburg)

  • Tobias Hoffmann

    (Centre for Biological Threats and Special Pathogens 4, Robert Koch-Institute)

  • Jana Scholz

    (Robert Koch-Institute)

  • Florian Melerowicz

    (Robert Koch-Institute)

  • Tobias Steinfeldt

    (Medical Center University of Freiburg
    University of Freiburg)

  • Frank Seeber

    (Robert Koch-Institute)

  • Martin Blume

    (Robert Koch-Institute)

Abstract

The apicomplexan parasite Toxoplasma gondii forms bradyzoite-containing tissue cysts that cause chronic and drug-tolerant infections. However, current in vitro models do not allow long-term culture of these cysts to maturity. Here, we developed a human myotube-based in vitro culture model of functionally mature tissue cysts that are orally infectious to mice and tolerate exposure to a range of antibiotics and temperature stresses. Metabolomic characterization of purified cysts reveals global changes that comprise increased levels of amino acids and decreased abundance of nucleobase- and tricarboxylic acid cycle-associated metabolites. In contrast to fast replicating tachyzoite forms of T. gondii these tissue cysts tolerate exposure to the aconitase inhibitor sodium fluoroacetate. Direct access to persistent stages of T. gondii under defined cell culture conditions will be essential for the dissection of functionally important host-parasite interactions and drug evasion mechanisms. It will also facilitate the identification of new strategies for therapeutic intervention.

Suggested Citation

  • Céline Christiansen & Deborah Maus & Ellen Hoppenz & Mateo Murillo-León & Tobias Hoffmann & Jana Scholz & Florian Melerowicz & Tobias Steinfeldt & Frank Seeber & Martin Blume, 2022. "In vitro maturation of Toxoplasma gondii bradyzoites in human myotubes and their metabolomic characterization," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28730-w
    DOI: 10.1038/s41467-022-28730-w
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    References listed on IDEAS

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    1. Barbara A. Fox & David J. Bzik, 2002. "De novo pyrimidine biosynthesis is required for virulence of Toxoplasma gondii," Nature, Nature, vol. 415(6874), pages 926-929, February.
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    Cited by:

    1. Jin-Lei Wang & Ting-Ting Li & Hany M. Elsheikha & Qin-Li Liang & Zhi-Wei Zhang & Meng Wang & L. David Sibley & Xing-Quan Zhu, 2022. "The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Nicolas Dos Santos Pacheco & Albert Tell i Puig & Amandine Guérin & Matthew Martinez & Bohumil Maco & Nicolò Tosetti & Estefanía Delgado-Betancourt & Matteo Lunghi & Boris Striepen & Yi-Wei Chang & Do, 2024. "Sustained rhoptry docking and discharge requires Toxoplasma gondii intraconoidal microtubule-associated proteins," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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