Glycerophosphocholine provision rescues Candida albicans growth and signaling phenotypes associated with phosphate limitation

DOI

10.1128/msphere.00231-23

Document Type

Journal Article

Publication Date

12-1-2023

Publication Title

mSphere

Volume

8

Issue

6

Keywords

Candida albicans, cell signaling, glycerophosphodiesters, phosphate, phosphate metabolism, phospholipids

Abstract

The fungal pathogen Candida albicans must acquire phosphate to colonize, infect, and proliferate in the human host. C. albicans has four inorganic phosphate (Pi) transporters, Pho84 being the major high-affinity transporter; its cells can also use glycerophosphocholine (GPC) as their sole phosphate source. GPC is a lipid metabolite derived from deacylation of the lipid phosphatidylcholine. GPC is found in multiple human tissues, including the renal medulla, where it acts as an osmolyte. C. albicans imports GPC into the cell via the Git3 and Git4 transporters. Internalized GPC can be hydrolyzed to release Pi. To determine if GPC import and subsequent metabolism affect phosphate homeostasis upon Pi limitation, we monitored growth and phenotypic outputs in cells provided with either Pi or GPC. In pho84?/? mutant cells that exhibit phenotypes associated with Pi limitation, GPC provision rescued sensitivity to osmotic and cell wall stresses. The glycerophosphodiesterase Gde1 was required for phenotypic rescue of osmotic stress by GPC provision. GPC provision, like Pi provision, resulted in repression of the PHO regulon and activation of TORC1 signaling. Pi uptake was similar to GPC uptake when phosphate availability was low (200 µM). While available at lower concentrations than Pi in the human host, GPC is an advantageous Pi source for the fungus because it simultaneously serves as a choline source. In summary, we find GPC is capable of substituting for Pi in C. albicans by many though not all criteria and may contribute to phosphate availability for the fungus in the human host.

Open Access

Gold

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