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Cryptococcus neoformans adapts to the host environment through TOR-mediated remodeling of phospholipid asymmetry

Author

Listed:
  • Laura C. Ristow

    (University of Iowa)

  • Andrew J. Jezewski

    (University of Iowa)

  • Benjamin J. Chadwick

    (University of Georgia)

  • Mark A. Stamnes

    (University of Iowa)

  • Xiaorong Lin

    (University of Georgia
    University of Georgia)

  • Damian J. Krysan

    (University of Iowa
    University of Iowa
    University of Iowa)

Abstract

Cryptococcus spp. are environmental fungi that first must adapt to the host environment before they can cause life-threatening meningitis in immunocompromised patients. Host CO2 concentrations are 100-fold higher than the external environment and strains unable to grow at host CO2 concentrations are not pathogenic. Using a genetic screening and transcriptional profiling approach, we report that the TOR pathway is critical for C. neoformans adaptation to host CO2 partly through Ypk1-dependent remodeling of phosphatidylserine asymmetry at the plasma membrane. We also describe a C. neoformans ABC/PDR transporter (PDR9) that is highly expressed in CO2-sensitive environmental strains, suppresses CO2-induced phosphatidylserine/phospholipid remodeling, and increases susceptibility to host concentrations of CO2. Interestingly, regulation of plasma membrane lipid asymmetry by the TOR-Ypk1 axis is distinct in C. neoformans compared to S. cerevisiae. Finally, host CO2 concentrations suppress the C. neoformans pathways that respond to host temperature (Mpk1) and pH (Rim101), indicating that host adaptation requires a stringent balance among distinct stress responses.

Suggested Citation

  • Laura C. Ristow & Andrew J. Jezewski & Benjamin J. Chadwick & Mark A. Stamnes & Xiaorong Lin & Damian J. Krysan, 2023. "Cryptococcus neoformans adapts to the host environment through TOR-mediated remodeling of phospholipid asymmetry," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42318-y
    DOI: 10.1038/s41467-023-42318-y
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    References listed on IDEAS

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    1. Kyung-Tae Lee & Yee-Seul So & Dong-Hoon Yang & Kwang-Woo Jung & Jaeyoung Choi & Dong-Gi Lee & Hyojeong Kwon & Juyeong Jang & Li Li Wang & Soohyun Cha & Gena Lee Meyers & Eunji Jeong & Jae-Hyung Jin & , 2016. "Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans," Nature Communications, Nature, vol. 7(1), pages 1-16, November.
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