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

9Citations
Citations of this article
12Readers
Mendeley users who have this article in their library.

This article is free to access.

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.

Cite

CITATION STYLE

APA

Ristow, L. C., Jezewski, A. J., Chadwick, B. J., Stamnes, M. A., Lin, X., & Krysan, D. J. (2023). Cryptococcus neoformans adapts to the host environment through TOR-mediated remodeling of phospholipid asymmetry. Nature Communications, 14(1). https://doi.org/10.1038/s41467-023-42318-y

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free