Candida albicans reprioritizes metal handling during fluconazole stress.

Published

Journal Article

Maintenance of metal homeostasis is critical to cell survival due to the multitude of cellular processes that depend on one or more metal cofactors. Here, we show that the opportunistic fungal pathogen Candida albicans extensively remodels its metal homeostasis networks to respond to treatment with the antifungal drug fluconazole. Disruption of the ergosterol biosynthetic pathway by fluconazole requires C. albicans adaptation, including increased Cu import and storage, increased retention of Fe, Mn, and Zn, altered utilization of Cu- and Mn-dependent enzymes, mobilization of Fe stores, and increased production of the heme prosthetic group utilized by the enzyme target of fluconazole. The findings offer a new perspective for thinking about fungal response to drug stress that pushes cells out of their metal homeostatic zones, leading them to enact metal-associated adaptation mechanisms to restore homeostasis to survive.

Full Text

Duke Authors

Cited Authors

  • Hunsaker, EW; Franz, KJ

Published Date

  • November 11, 2019

Published In

PubMed ID

  • 31709426

Pubmed Central ID

  • 31709426

Electronic International Standard Serial Number (EISSN)

  • 1756-591X

International Standard Serial Number (ISSN)

  • 1756-5901

Digital Object Identifier (DOI)

  • 10.1039/c9mt00228f

Language

  • eng