ArticleFungal genetics and biology : FG & B2020
Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans.
Article in Fungal genetics and biology : FG & B, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 56 citations in OpenAlex.
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- In vitro and in vivo efficacy of the antimycobacterial molecule SQ109 against the human pathogenic fungus, Cryptococcus neoformans.PLoS neglected tropical diseases · 2025Article
- Impact of ERG6 Gene Deletion on Membrane Composition and Properties in the Pathogenic Yeast Candida glabrata.Cell biochemistry and biophysics · 2025Article
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- Is a Fungal Apocalypse Inevitable or Just a Hallucination? An Overview of the Antifungal Armamentarium Used in the Fight against Pathogenic Fungi.ACS medicinal chemistry letters · 2025Review
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- Diverse signatures of convergent evolution in cactus-associated yeasts.PLoS biology · 2024Article
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- Azole resistance in Aspergillus fumigatus- comprehensive review.Archives of microbiology · 2024Review
- The sterol C-24 methyltransferase encoding gene, erg6, is essential for viability of Aspergillus species.Nature communications · 2024Article
- Genome-wide identification of resistance genes and response mechanism analysis of key gene knockout strain to catechol inFrontiers in microbiology · 2024Article
- Isobavachalcone exhibits antifungal and antibiofilm effects againstFrontiers in cellular and infection microbiology · 2024Article
- Diverse signatures of convergent evolution in cacti-associated yeasts.bioRxiv : the preprint server for biology · 2023Article
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- Dual mechanisms of cholesterol-GPCR interactions that depend on membrane phospholipid composition.Structure (London, England : 1993) · 2023Article
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Ergosterol is the most important membrane sterol in fungal cells and a component not found in the membranes of human cells. We identified the ERG6 gene in the AIDS-associated fungal pathogen, Cryptococcus neoformans, encoding the sterol C-24 methyltransferase of fungal ergosterol biosynthesis. In this work, we have explored its relationship with high-temperature growth and virulence of C. neoformans by the construction of a loss-of-function mutant. In contrast to other genes involved in ergosterol biosynthesis, C. neoformans ERG6 is not essential for growth under permissive conditions in vitro. However, the erg6 mutant displayed impaired thermotolerance and increased susceptibility to osmotic and oxidative stress, as well as to different antifungal drugs. Total lipid analysis demonstrated a decrease in the erg6Δ strain membrane ergosterol content. In addition, this mutant strain was avirulent in an invertebrate model of C. neoformans infection. C. neoformans Erg6 was cyto-localized in the endoplasmic reticulum and Golgi complex. Our results demonstrate that Erg6 is crucial for growth at high temperature and virulence, likely due to its effects on C. neoformans membrane integrity and dynamics. These pathogen-focused investigations into ergosterol biosynthetic pathway components reinforce the multiple roles of ergosterol in the response of diverse fungal species to alterations in the environment, especially that of the infected host. These studies open perspectives to understand the participation of ergosterol in mechanism of resistance to azole and polyene drugs. Observed synergistic growth defects with co-inhibition of Erg6 and other components of the ergosterol biosynthesis pathway suggests novel approaches to treatment in human fungal infections.
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