ArticleFungal genetics and biology : FG & B2015
Leu1 plays a role in iron metabolism and is required for virulence in Cryptococcus neoformans.
Article in Fungal genetics and biology : FG & B, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Single nucleotide polymorphisms are associated with strain-specific virulence differences among clinical isolates of Cryptococcus neoformans.Nature communications · 2024Pooled it
- Acidic pH Reduces Fluconazole Susceptibility inJournal of microbiology and biotechnology · 2025Article
- The Response ofJournal of fungi (Basel, Switzerland) · 2023Article
- FgLEU1 Is Involved in Leucine Biosynthesis, Sexual Reproduction, and Full Virulence inJournal of fungi (Basel, Switzerland) · 2022Article
- Exposure of Candida parapsilosis to the silver(I) compound SBC3 induces alterations in the proteome and reduced virulence.Metallomics : integrated biometal science · 2022Article
- Molecular targets for antifungals in amino acid and protein biosynthetic pathways.Amino acids · 2021Review
- Article
- Involvement of Mrs3/4 in Mitochondrial Iron Transport and Metabolism inJournal of microbiology and biotechnology · 2020Article
- Effects of Iron Deficiency on Serum Metabolome, Hepatic Histology, and Function in Neonatal Piglets.Animals : an open access journal from MDPI · 2020Article
- A Transcriptional Regulatory Map of Iron Homeostasis Reveals a New Control Circuit for Capsule Formation inGenetics · 2020Article
- Article
- Leucine biosynthesis is required for infection-related morphogenesis and pathogenicity in the rice blast fungus Magnaporthe oryzae.Current genetics · 2020Article
- Biosynthesis of Amino Acids inMicroorganisms · 2019Article
- The leucine biosynthetic pathway is crucial for adaptation to iron starvation and virulence inVirulence · 2019Article
- The Zn2Cys6-type transcription factor LeuB cross-links regulation of leucine biosynthesis and iron acquisition in Aspergillus fumigatus.PLoS genetics · 2018Article
- Investigation of Cryptococcus neoformans magnesium transporters reveals important role of vacuolar magnesium transporter in regulating fungal virulence factors.MicrobiologyOpen · 2018Article
- The mitochondrial ABC transporter Atm1 plays a role in iron metabolism and virulence in the human fungal pathogen Cryptococcus neoformans.Medical mycology · 2018Article
- Vacuolar zinc transporter Zrc1 is required for detoxification of excess intracellular zinc in the human fungal pathogen Cryptococcus neoformans.Journal of microbiology (Seoul, Korea) · 2018Article
- Comparison of Healthy and Dandruff Scalp Microbiome Reveals the Role of Commensals in Scalp Health.Frontiers in cellular and infection microbiology · 2018Article
- The lysine biosynthetic enzyme Lys4 influences iron metabolism, mitochondrial function and virulence in Cryptococcus neoformans.Biochemical and biophysical research communications · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
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Abstract
Amino acid biosynthetic pathways that are absent in mammals are considered an attractive target for antifungal therapy. Leucine biosynthesis is one such target pathway, consisting of a five-step conversion process starting from the valine precursor 2-keto-isovalerate. Isopropylmalate dehydrogenase (Leu1) is an Fe-S cluster protein that is required for leucine biosynthesis in the model fungus Saccharomyces cerevisiae. The human pathogenic fungus Cryptococcus neoformans possesses an ortholog of S. cerevisiae Leu1, and our previous transcriptome data showed that the expression of LEU1 is regulated by iron availability. In this study, we characterized the role of Leu1 in iron homeostasis and the virulence of C. neoformans. We found that deletion of LEU1 caused leucine auxotrophy and that Leu1 may play a role in the mitochondrial-cytoplasmic Fe-S cluster balance. Whereas cytoplasmic Fe-S protein levels were not affected, mitochondrial Fe-S proteins were up-regulated in the leu1 mutant, suggesting that Leu1 mainly influences mitochondrial iron metabolism. The leu1 mutant also displayed increased sensitivity to oxidative stress and cell wall/membrane disrupting agents, which may have been caused by mitochondrial dysfunction. Furthermore, the leu1 mutant was deficient in capsule formation and showed attenuated virulence in a mouse inhalation model of cryptococcosis. Overall, our results indicate that Leu1 plays a role in iron metabolism and is required for virulence in C. neoformans.
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