Crosstalk between the calcineurin and cell wall integrity pathways prevents chitin overexpression in Candida albicans.

Autor:	da Silva Dantas A; School of Biosciences, University of Exeter, Geoffrey Pope Building, Exeter EX4 4QD, UK.; School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK., Nogueira F; School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.; Children's Cancer Research Institute, Labdia and Max F. Perutz Laboratories, Vienna 1090, Austria., Lee KK; School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.; NGeneBio Company, 288 Digital-ro, Guro-gu, Seoul 08390, South Korea., Walker LA; School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK., Edmondson M; School of Biosciences, University of Exeter, Geoffrey Pope Building, Exeter EX4 4QD, UK., Brand AC; School of Biosciences, University of Exeter, Geoffrey Pope Building, Exeter EX4 4QD, UK.; School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK., Lenardon MD; School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia., Gow NAR; School of Biosciences, University of Exeter, Geoffrey Pope Building, Exeter EX4 4QD, UK.; School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2021 Dec 15; Vol. 134 (24). Date of Electronic Publication: 2021 Dec 16.
DOI:	10.1242/jcs.258889
Abstrakt:	Echinocandins such as caspofungin are frontline 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 upregulation of chitin synthesis, thereby sustaining cell wall integrity (CWI). 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 subpopulation 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 supra-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. This article has an associated First Person interview with the first author of the paper. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2021. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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