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Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages

Author

Listed:
  • Yifan Wang

    (University of California, Davis)

  • Lamba Omar Sangaré

    (University of California, Davis)

  • Tatiana C. Paredes-Santos

    (University of California, Davis)

  • Musa A. Hassan

    (The University of Edinburgh
    The University of Edinburgh
    The University of Edinburgh)

  • Shruthi Krishnamurthy

    (University of California, Davis)

  • Anna M. Furuta

    (University of California, Davis)

  • Benedikt M. Markus

    (Whitehead Institute for Biomedical Research
    University of Freiburg)

  • Sebastian Lourido

    (Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology)

  • Jeroen P. J. Saeij

    (University of California, Davis)

Abstract

Macrophages play an essential role in the early immune response against Toxoplasma and are the cell type preferentially infected by the parasite in vivo. Interferon gamma (IFNγ) elicits a variety of anti-Toxoplasma activities in macrophages. Using a genome-wide CRISPR screen we identify 353 Toxoplasma genes that determine parasite fitness in naїve or IFNγ-activated murine macrophages, seven of which are further confirmed. We show that one of these genes encodes dense granule protein GRA45, which has a chaperone-like domain, is critical for correct localization of GRAs into the PVM and secretion of GRA effectors into the host cytoplasm. Parasites lacking GRA45 are more susceptible to IFNγ-mediated growth inhibition and have reduced virulence in mice. Together, we identify and characterize an important chaperone-like GRA in Toxoplasma and provide a resource for the community to further explore the function of Toxoplasma genes that determine fitness in IFNγ-activated macrophages.

Suggested Citation

  • Yifan Wang & Lamba Omar Sangaré & Tatiana C. Paredes-Santos & Musa A. Hassan & Shruthi Krishnamurthy & Anna M. Furuta & Benedikt M. Markus & Sebastian Lourido & Jeroen P. J. Saeij, 2020. "Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18991-8
    DOI: 10.1038/s41467-020-18991-8
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    Cited by:

    1. Dana Aghabi & Megan Sloan & Grace Gill & Elena Hartmann & Olga Antipova & Zhicheng Dou & Alfredo J. Guerra & Vern B. Carruthers & Clare R. Harding, 2023. "The vacuolar iron transporter mediates iron detoxification in Toxoplasma gondii," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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