Grf10 regulates the response to copper, iron, and phosphate in Candida albicans

Wangsanut, Tanaporn; Arnold, Sylvia J. Y.; Jilani, Safia Z.; Marzec, Sarah; Monsour, Robert C.; Rolfes, Ronda J.; Hoffman, ed., C.

doi:10.1093/g3journal/jkad070

Title: Grf10 regulates the response to copper, iron, and phosphate in Candida albicans

Journal Article · Sun Mar 26 00:00:00 EDT 2023 · G3

DOI:https://doi.org/10.1093/g3journal/jkad070· OSTI ID:2310434

Wangsanut, Tanaporn; Arnold, Sylvia J. Y.; Jilani, Safia Z.; Marzec, Sarah; Monsour, Robert C.; Rolfes, Ronda J.; Hoffman, ed., C.

Abstract The pathogenic yeast, Candida albicans, and other microbes must be able to handle drastic changes in nutrient availability within the human host. Copper, iron, and phosphate are essential micronutrients for microbes that are sequestered by the human host as nutritional immunity; yet high copper levels are employed by macrophages to induce toxic oxidative stress. Grf10 is a transcription factor important for regulating genes involved in morphogenesis (filamentation, chlamydospore formation) and metabolism (adenylate biosynthesis, 1-carbon metabolism). The grf10Δ mutant exhibited resistance to excess copper in a gene dosage-dependent manner but grew the same as the wild type in response to other metals (calcium, cobalt, iron, manganese, and zinc). Point mutations in the conserved residues D302 and E305, within a protein interaction region, conferred resistance to high copper and induced hyphal formation similar to strains with the null allele. The grf10Δ mutant misregulated genes involved with copper, iron, and phosphate uptake in YPD medium and mounted a normal transcriptional response to high copper. The mutant accumulated lower levels of magnesium and phosphorus, suggesting that copper resistance is linked to phosphate metabolism. Our results highlight new roles for Grf10 in copper and phosphate homeostasis in C. albicans and underscore the fundamental role of Grf10 in connecting these with cell survival.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: FG02-07ER15895; SC0021218

OSTI ID:: 2310434

Journal Information:: G3, Journal Name: G3 Vol. 13 Journal Issue: 6; ISSN 2160-1836

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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