ArticleThe Journal of clinical investigation2007
Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
82 citing papers in PubMed, 134 citations in OpenAlex.
- Investigating the therapeutic potential of the antibacterial drug nitroxoline in combating cryptococcal infection.PLoS neglected tropical diseases · 2026Article
- A cysteine-rich domain of themBio · 2026Article
- Article
- Cryptococcal nutrient acquisition and pathogenesis: dining on the host.Microbiology and molecular biology reviews : MMBR · 2025Review
- Copper acquisition is essential for plant colonization and virulence in a root-infecting vascular wilt fungus.PLoS pathogens · 2024Article
- Insights into copper sensing and tolerance inFrontiers in microbiology · 2024Article
- How metals fuel fungal virulence, yet promote anti-fungal immunity.Disease models & mechanisms · 2023Review
- Metals and the cell surface of Cryptococcus neoformans.Current opinion in microbiology · 2023Review
- A Comprehensive Review on the Roles of Metals Mediating Insect-Microbial Pathogen Interactions.Metabolites · 2023Review
- Identification and Characterization of the Determinants of Copper Resistance in the Acidophilic FungusApplied and environmental microbiology · 2023Article
- Article
- The Combination of Iron and Copper Increases Pathogenicity and Induces Proteins Related to the Main Virulence Factors in Clinical Isolates ofJournal of fungi (Basel, Switzerland) · 2022Article
- Copper Metabolism inFrontiers in cell and developmental biology · 2022Article
- Article
- Expanded role of the Cu-sensing transcription factor Mac1p in Candida albicans.Molecular microbiology · 2020Article
- Review
- Structural and Functional Diversity Among the Members of CTR, the Membrane Copper Transporter Family.The Journal of membrane biology · 2020Review
- Role of the ESCRT Pathway in Laccase Trafficking and Virulence of Cryptococcus neoformans.Infection and immunity · 2020Article
- Copper Sources for Sod1 Activation.Antioxidants (Basel, Switzerland) · 2020Review
- A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis.Nature chemical biology · 2020Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The study of regulatory networks in human pathogens such as Cryptococcus neoformans provides insights into host-pathogen interactions that may allow for correlation of gene expression patterns with clinical outcomes. In the present study, deletion of the cryptococcal copper-dependent transcription factor 1 (Cuf1) led to defects in growth and virulence factor expression in low copper conditions. In mouse models, cuf1Delta strains exhibited reduced dissemination to the brain, but no change in lung growth, suggesting copper is limiting in neurologic infections. To examine this further, a biologic probe of available copper was constructed using the cryptococcal CUF1-dependent copper transporter, CTR4. Fungal cells demonstrated high CTR4 expression levels after phagocytosis by macrophage-like J774.16 cells and during infection of mouse brains, but not lungs, consistent with limited copper availability during neurologic infection. This was extended to human brain infections by demonstrating CTR4 expression during C. neoformans infection of an AIDS patient. Moreover, high CTR4 expression by cryptococcal strains from 24 solid organ transplant patients was associated with dissemination to the CNS. Our results suggest that copper acquisition plays a central role in fungal pathogenesis during neurologic infection and that measurement of stable traits such as CTR4 expression may be useful for risk stratification of individuals with cryptococcosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.