ArticleMolecular biology of the cell2016
Pho4 mediates phosphate acquisition in Candida albicans and is vital for stress resistance and metal homeostasis.
Article in Molecular biology of the cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 59 citations in OpenAlex.
- Oxidative stress-responsive cell wall remodeling depends on phosphate in Candida albicans.Nature communications · 2026Article
- Article
- The transcriptional response to environmental alkalization involves both Komagataella phaffii Pho4 transcription factors.Microbial cell factories · 2026Article
- Beyond phosphate uptake: PT4/PT11 as key functional components linking phosphate acquisition, nutrient exchange, and arbuscule maintenance in arbuscular mycorrhizal symbiosis.Frontiers in plant science · 2026Review
- Multilayered Regulation of Fungal Phosphate Metabolism: From Molecular Mechanisms to Ecological Roles in the Global Phosphorus Cycle.Life (Basel, Switzerland) · 2025Review
- Phosphorus-solubilizing fungi improve growth and P nutrition in sorghum at variable salinity levels.Environmental microbiome · 2025Article
- Polyphosphatases have a polyphosphate-independent influence on the virulence ofInfection and immunity · 2025Article
- An Introduction to the Influence of Nutritional Factors on the Pathogenesis of Opportunist Fungal Pathogens in Humans.Pathogens (Basel, Switzerland) · 2025Review
- Echinocandin Adaptation inJournal of fungi (Basel, Switzerland) · 2025Article
- Candida albicans' inorganic phosphate transport and evolutionary adaptation to phosphate scarcity.PLoS genetics · 2024Article
- A COmBio · 2024Article
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- Glycerophosphocholine provision rescuesmSphere · 2023Article
- Divergence of TORC1-mediated stress response leads to novel acquired stress resistance in a pathogenic yeast.PLoS pathogens · 2023Article
- Divergence of TORC1-mediated Stress Response Leads to Novel Acquired Stress Resistance in a Pathogenic Yeast.bioRxiv : the preprint server for biology · 2023Article
- Grf10 regulates the response to copper, iron, and phosphate in Candida albicans.G3 (Bethesda, Md.) · 2023Article
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- Phosphate accumulation in rice leaves promotes fungal pathogenicity and represses host immune responses during pathogen infection.Frontiers in plant science · 2023Article
- Article
- The phosphate language of fungi.Trends in microbiology · 2022Review
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
During interactions with its mammalian host, the pathogenic yeast Candida albicans is exposed to a range of stresses such as superoxide radicals and cationic fluxes. Unexpectedly, a nonbiased screen of transcription factor deletion mutants revealed that the phosphate-responsive transcription factor Pho4 is vital for the resistance of C. albicans to these diverse stresses. RNA-Seq analysis indicated that Pho4 does not induce stress-protective genes directly. Instead, we show that loss of Pho4 affects metal cation toxicity, accumulation, and bioavailability. We demonstrate that pho4Δ cells are sensitive to metal and nonmetal cations and that Pho4-mediated polyphosphate synthesis mediates manganese resistance. Significantly, we show that Pho4 is important for mediating copper bioavailability to support the activity of the copper/zinc superoxide dismutase Sod1 and that loss of Sod1 activity contributes to the superoxide sensitivity of pho4Δ cells. Consistent with the key role of fungal stress responses in countering host phagocytic defenses, we also report that C. albicans pho4Δ cells are acutely sensitive to macrophage-mediated killing and display attenuated virulence in animal infection models. The novel connections between phosphate metabolism, metal homeostasis, and superoxide stress resistance presented in this study highlight the importance of metabolic adaptation in promoting C. albicans survival in the host.
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