Crosstalk between calcineurin and the cell wall integrity pathways prevents chitin overexpression in Candida albicans.
Alessandra da Silva DantasFilomena NogueiraKeunsook K LeeLouise A WalkerMatt EdmondsonAlexandra C BrandMegan D LenardonNeil A R GowPublished in: Journal of cell science (2021)
Echinocandins such as caspofungin are front line antifungal drugs that compromise β-1,3 glucan synthesis in the cell wall. Recent reports have shown that fungal cells can resist killing by caspofungin by up-regulation of chitin synthesis, thereby sustaining cell wall integrity. When echinocandins are removed, the chitin content of cells quickly returns to basal levels, suggesting that there is a fitness cost associated with having elevated levels of chitin in the cell wall. We show here that simultaneous activation of the calcineurin and CWI pathways generates a sub-population of Candida albicans yeast cells that have supra-normal chitin levels interspersed throughout the inner and outer cell wall, and that these cells are non-viable, perhaps due to loss of wall elasticity required for cell expansion and growth. Mutations in the Ca2+-calcineurin pathway prevented the formation of these non-viable super high chitin cells by negatively regulating chitin synthesis driven by the CWI pathway. The Ca2+-calcineurin pathway may therefore act as an attenuator that prevents the overproduction of chitin by coordinating both chitin upregulation and negative regulation of the CWI signaling pathway.
Keyphrases
- cell wall
- induced apoptosis
- candida albicans
- signaling pathway
- cell cycle arrest
- staphylococcus aureus
- endoplasmic reticulum stress
- cell death
- biofilm formation
- oxidative stress
- pi k akt
- emergency department
- single cell
- physical activity
- body composition
- epithelial mesenchymal transition
- long non coding rna
- mouse model
- pseudomonas aeruginosa
- bone marrow
- transcription factor