Grf10 regulates the response to copper, iron, and phosphate in <i>Candida albicans</i>

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

doi:10.1093/g3journal/jkad070

Cited by 4 publications

(2 citation statements)

References 75 publications

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“…The resulting cultures were designated as EX1, EX2, EX3, UN1, UN2, and UN3 isolates. The DNA of each isolate was extracted as detailed in ( Wangsanut et al., 2023 ).…”

Section: Methodsmentioning

confidence: 99%

Adaptation to an amoeba host drives selection of virulence-associated traits and genetic variation in saprotrophic Candida albicans

Amsri,

Pruksaphon,

Thammasit

et al. 2024

Front. Cell. Infect. Microbiol.

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Amoebae are micropredators that play an important role in controlling fungal populations in ecosystems. However, the interaction between fungi and their amoebic predators suggests that the pressure from predatory selection can significantly influence the development of fungal virulence and evolutionary processes. Thus, the purpose of this study was to investigate the adaptation of saprotrophic Candida albicans strains during their interactions with Acanthamoeba castellanii. We conducted a comprehensive analysis of survival after co-culture by colony counting of the yeast cells and examining yeast cell phenotypic and genetic characteristics. Our results indicated that exposure to amoebae enhanced the survival capacity of environmental C. albicans and induced visible morphological alterations in C. albicans, particularly by an increase in filamentation. These observed phenotypic changes were closely related to concurrent genetic variations. Notably, mutations in genes encoding transcriptional repressors (TUP1 and SSN6), recognized for their negative regulation of filamentous growth, were exclusively identified in amoeba-passaged isolates, and absent in unexposed isolates. Furthermore, these adaptations increased the exposed isolates’ fitness against various stressors, simultaneously enhancing virulence factors and demonstrating an increased ability to invade A549 lung human epithelial cells. These observations indicate that the sustained survival of C. albicans under ongoing amoebic predation involved a key role of mutation events in microevolution to modulate the ability of these isolates to change phenotype and increase their virulence factors, demonstrating an enhanced potential to survive in diverse environmental niches.

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“…The resulting cultures were designated as EX1, EX2, EX3, UN1, UN2, and UN3 isolates. The DNA of each isolate was extracted as detailed in ( Wangsanut et al., 2023 ).…”

Section: Methodsmentioning

confidence: 99%

Adaptation to an amoeba host drives selection of virulence-associated traits and genetic variation in saprotrophic Candida albicans

Amsri,

Pruksaphon,

Thammasit

et al. 2024

Front. Cell. Infect. Microbiol.

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“…Disruption of this control is one possible target of acetal toxicity. At the same time, adenine availability suppresses activation of the purine biosynthetic pathway via the transcription factors Grf10 and Bas1 [69], which also control one-carbon metabolism and phosphate, copper and iron responses [70]. A related control system exists in S. cerevisiae where an intermediate of the adenine biosynthetic pathway, ZMP, controls NAD + biosynthesis as well [71].…”

Section: Plos Onementioning

confidence: 99%

Lethal metabolism of Candida albicans respiratory mutants

Kane,

Burke,

Diaz

et al. 2024

PLoS ONE

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The destructive impact of fungi in agriculture and animal and human health, coincident with increases in antifungal resistance, underscores the need for new and alternative drug targets to counteract these trends. Cellular metabolism relies on many intermediates with intrinsic toxicity and promiscuous enzymatic activity generates others. Fuller knowledge of these toxic entities and their generation may offer opportunities of antifungal development. From this perspective our observation of media-conditional lethal metabolism in respiratory mutants of the opportunistic fungal pathogen Candida albicans was of interest. C. albicans mutants defective in NADH:ubiquinone oxidoreductase (Complex I of the electron transport chain) exhibit normal growth in synthetic complete medium. In YPD medium, however, the mutants grow normally until early stationary phase whereupon a dramatic loss of viability occurs. Upwards of 90% of cells die over the subsequent four to six hours with a loss of membrane integrity. The extent of cell death was proportional to the amount of BactoPeptone, and to a lesser extent, the amount of yeast extract. YPD medium conditioned by growth of the mutant was toxic to wild-type cells indicating mutant metabolism established a toxic milieu in the media. Conditioned media contained a volatile component that contributed to toxicity, but only in the presence of a component of BactoPeptone. Fractionation experiments revealed purine nucleosides or bases as the synergistic component. GC-mass spectrometry analysis revealed acetal (1,1-diethoxyethane) as the active volatile. This previously unreported and lethal synergistic interaction of acetal and purines suggests a hitherto unrecognized toxic metabolism potentially exploitable in the search for antifungal targets.

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

Wangsanut

Arnold

Jilani

et al. 2023

G3: Genes, Genomes, Genetics

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

Cited by 4 publications

References 75 publications

Adaptation to an amoeba host drives selection of virulence-associated traits and genetic variation in saprotrophic Candida albicans

Adaptation to an amoeba host drives selection of virulence-associated traits and genetic variation in saprotrophic Candida albicans

Lethal metabolism of Candida albicans respiratory mutants

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

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