Evidence map›Paper›PMID 21441208›Full record

ArticleGenetics2011

Nitrogen metabolite repression of metabolism and virulence in the human fungal pathogen Cryptococcus neoformans.

I Russel Lee, Eve W L Chow, Carl A Morrow, Julianne T Djordjevic, James A Fraser

Open access · bronzeAbstract read
In one paragraph

Article in Genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.6field-weighted citation impact, top 7% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 81 citations in OpenAlex.

  1. Article
  2. Article
  3. Cryptococcal nutrient acquisition and pathogenesis: dining on the host.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  4. Article
  5. Unveiling new features of the human pathogenComputational and structural biotechnology journal · 2025
    Article
  6. Exposure of Cryptococcus neoformans to low nitrogen levels enhances virulence.International microbiology : the official journal of the Spanish Society for Microbiology · 2024
    Article
  7. Article
  8. Pleiotropic roles of LAMMER kinase, Lkh1 in stress responses and virulence ofFrontiers in cellular and infection microbiology · 2024
    Article
  9. A Limited Number of Amino Acid Permeases Are Crucial forInternational journal of microbiology · 2024
    Review
  10. Proteomics ofJournal of fungi (Basel, Switzerland) · 2023
    Article
  11. Article
  12. Article
  13. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

I Russel LeeAustralian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia.
Eve W L Chow
Carl A Morrow
Julianne T Djordjevic
James A Fraser
The University of Queensland · AUWestmead Institute · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Proper regulation of metabolism is essential to maximizing fitness of organisms in their chosen environmental niche. Nitrogen metabolite repression is an example of a regulatory mechanism in fungi that enables preferential utilization of easily assimilated nitrogen sources, such as ammonium, to conserve resources. Here we provide genetic, transcriptional, and phenotypic evidence of nitrogen metabolite repression in the human pathogen Cryptococcus neoformans. In addition to loss of transcriptional activation of catabolic enzyme-encoding genes of the uric acid and proline assimilation pathways in the presence of ammonium, nitrogen metabolite repression also regulates the production of the virulence determinants capsule and melanin. Since GATA transcription factors are known to play a key role in nitrogen metabolite repression, bioinformatic analyses of the C. neoformans genome were undertaken and seven predicted GATA-type genes were identified. A screen of these deletion mutants revealed GAT1, encoding the only global transcription factor essential for utilization of a wide range of nitrogen sources, including uric acid, urea, and creatinine-three predominant nitrogen constituents found in the C. neoformans ecological niche. In addition to its evolutionarily conserved role in mediating nitrogen metabolite repression and controlling the expression of catabolic enzyme and permease-encoding genes, Gat1 also negatively regulates virulence traits, including infectious basidiospore production, melanin formation, and growth at high body temperature (39°-40°). Conversely, Gat1 positively regulates capsule production. A murine inhalation model of cryptococcosis revealed that the gat1Δ mutant is slightly more virulent than wild type, indicating that Gat1 plays a complex regulatory role during infection.

Indexed as

Amino Acid SequenceAnimalsCaenorhabditis elegansCryptococcosisCryptococcus neoformansFemaleFungal ProteinsGATA Transcription FactorsGene Expression Regulation, FungalGenetic Complementation TestHumansMelaninsMembrane Transport ProteinsMiceMice, Inbred BALB CMolecular Sequence DataFungal ProteinsGAT1 protein, Cryptococcus neoformansGATA Transcription FactorsMelaninsMembrane Transport ProteinsNitrogenPolysaccharidesQuaternary Ammonium CompoundsUrate OxidaseUreaseUric Acid

Identifiers

PMID21441208
PMCPMC3122321
OpenAlexW2127363691

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.