ArticleEukaryotic cell2009
Identification of ENA1 as a virulence gene of the human pathogenic fungus Cryptococcus neoformans through signature-tagged insertional mutagenesis.
Article in Eukaryotic cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 79 citations in OpenAlex.
- Systematic Profiling of Essential Fungal Transcription Factors Uncovers Ezt1 as a Central Pathobiological and Morphogenic Regulator inResearch square · 2026Article
- Systematic Profiling of Essential Fungal Transcription Factors Uncovers Ezt1 as a Central Pathobiological and Morphogenic Regulator inbioRxiv : the preprint server for biology · 2026Article
- ENA1 deficiency attenuates Saccharomyces 'boulardii' probiotic yeast virulence in immunosuppressed mouse fungaemia model.Communications biology · 2026Article
- Molecular Triggers of Yeast Pathogenicity in the Yeast-Host Interactions.Current issues in molecular biology · 2025Review
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- Gene-specific transcriptional activation by themSphere · 2024Article
- A trade-off between proliferation and defense in the fungal pathogenbioRxiv : the preprint server for biology · 2024Article
- Loss of a conserved C-terminal region of thebioRxiv : the preprint server for biology · 2024Article
- Phylogenetic and Structure-Function Analyses of ENA ATPases: A Case Study of the ENA1 Protein from the FungusInternational journal of molecular sciences · 2023Article
- Ena Proteins Respond to PacC-Mediated pH Signaling Pathway and Play a Crucial Role in Patulin Biosynthesis.Journal of fungi (Basel, Switzerland) · 2023Article
- Distinct Roles of Ena ATP Family Proteins in Sodium Accumulation, Invasive Growth, and Full Virulence inJournal of fungi (Basel, Switzerland) · 2023Article
- The translocated virulence protein VirD5 causes DNA damage and mutation duringScience advances · 2022Article
- Article
- Establishment of a Genetic Transformation System in Guanophilic FungusJournal of fungi (Basel, Switzerland) · 2021Article
- P-type NaVirulence · 2020Article
- Assessing the virulence of Cryptococcus neoformans causing meningitis in HIV infected and uninfected patients in Vietnam.Medical mycology · 2020Article
- Environmental Factors That Contribute to the Maintenance ofMicroorganisms · 2020Review
- Generation ofMicroorganisms · 2019Article
- Regulatory Mechanism of the Atypical AP-1-Like Transcription Factor Yap1 in Cryptococcus neoformans.mSphere · 2019Article
- Complementary Proteomics, Genomics approaches identifies potential pathogenicity/virulence factors in Tilletia indica induced under the influence of host factor.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
A library of more than 4,500 signature-tagged insertion mutants of the human pathogenic fungus Cryptococcus neoformans was generated, and a subset was screened in a murine inhalation model to identify genes required for virulence. New genes that regulate aspects of C. neoformans virulence were also identified by screening the entire library for in vitro phenotypes related to the ability to cause disease, including melanin production, growth at high temperature, and growth under conditions of nutrient limitation. A screen of 10% of the strain collection in mice identified an avirulent mutant strain with an insertion in the ENA1 gene, which is predicted to encode a fungus-specific sodium or potassium P-type ATPase. The results of the deletion of the gene and complementation experiments confirmed its key role in mammalian virulence. ena1 mutant strains exhibited no change in sensitivity to high salt concentrations but were sensitive to alkaline pH conditions, providing evidence that the fungus may have to survive at elevated pH during infection of the mammalian host. The mutation of the well-characterized virulence factor calcineurin (CNA1) also rendered C. neoformans strains sensitive to elevated pH. ENA1 transcripts in wild-type and cna1 mutant strains were upregulated in response to high pH, and cna1 ena1 double mutant strains exhibited increased sensitivity to elevated pH, indicating that at least two pathways in the fungus mediate survival under alkaline conditions. Signature-tagged mutagenesis is an effective strategy for the discovery of new virulence genes in fungal pathogens of animals.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.