Evidence map›Paper›PMID 11287622›Full record

ArticleMolecular and cellular biology2001

Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen Cryptococcus neoformans.

C A D'Souza, J A Alspaugh, C Yue, T Harashima, G M Cox, J R Perfect, J Heitman

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers.

0numbers the graph read from it
0cells of the map it votes in
194citing papers in PubMed
13.5field-weighted citation impact, top 1% 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

194 citing papers in PubMed, 324 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Regulation of melanin production in fungi.Frontiers in fungal biology · 2025
    Review
  6. Article
  7. Antifungal Resistance in Cryptococcal Infections.Pathogens (Basel, Switzerland) · 2024
    Review
  8. Article
  9. Article
  10. CryptoCEN: A Co-Expression Network forbioRxiv : the preprint server for biology · 2023
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Gene, virulence and related regulatory mechanisms inActa biochimica et biophysica Sinica · 2022
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Anticapsular and Antifungal Activity of α-Cyperone.Antibiotics (Basel, Switzerland) · 2021
    Article

134 more citing papers are in PubMed but not listed here.

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

7 authors at 2 institutions in 1 country.

C A D'SouzaDepartments of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.
J A Alspaugh
C Yue
T Harashima
G M Cox
J R Perfect
J Heitman
Duke University Hospital · USHoward Hughes Medical Institute · US

Funding

ROLE OF CALCINEURIN IN C. NEOFORMANS MATING AND FRUITINGR01AI039115 · NIAID · DUKE UNIVERSITY · PI HEITMAN, JOSEPH · 1997 to 2025
$6.7M
Genetics of Cryptococcus sexual reproductionR37AI039115 · NIAID · DUKE UNIVERSITY · PI HEITMAN, JOSEPH · 2011 to 2020
$4.9M
SIGNAL TRANSDUCTION PATHWAYS REGULATING VIRULENCEP01AI044975 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 1999 to 2003
$3.4M
Role of Calcineurin in Fungal VirulenceR01AI042159 · NIAID · DUKE UNIVERSITY · PI HEITMAN, JOSEPH · 1998 to 2009
$2.5M
SIGNAL TRANSDUCTION AND VIRULENCE IN C NEOFORMANSK08AI001556 · NIAID · DUKE UNIVERSITY · PI ALSPAUGH, J. ANDREW · 1998 to 2001
$220k
NIAID NIH HHS K08 AI01556NIAID NIH HHS P01 AI044975NIAID NIH HHS P01 AI44975NIAID NIH HHS R01 AI039115NIAID NIH HHS R01 AI042159NIAID NIH HHS R01 AI39115NIAID NIH HHS R01 AI42159NIAID NIH HHS R37 AI039115
6 · The paper itself

Abstract

Cryptococcus neoformans is an opportunistic fungal pathogen that infects the human central nervous system. This pathogen elaborates two specialized virulence factors: the antioxidant melanin and an antiphagocytic immunosuppressive polysaccharide capsule. A signaling cascade controlling mating and virulence was identified. The PKA1 gene encoding the major cyclic AMP (cAMP)-dependent protein kinase catalytic subunit was identified and disrupted. pka1 mutant strains were sterile, failed to produce melanin or capsule, and were avirulent. The PKR1 gene encoding the protein kinase A (PKA) regulatory subunit was also identified and disrupted. pkr1 mutant strains overproduced capsule and were hypervirulent in animal models of cryptococcosis. pkr1 pka1 double mutant strains exhibited phenotypes similar to that of pka1 mutants, providing epistasis evidence that the Pka1 catalytic subunit functions downstream of the Pkr1 regulatory subunit. The PKA pathway was also shown to function downstream of the Galpha protein Gpa1 and to regulate cAMP production by feedback inhibition. These findings define a Galpha protein-cAMP-PKA signaling pathway regulating differentiation and virulence of a human fungal pathogen.

Indexed as

GTP-Binding Protein alpha SubunitsSaccharomyces cerevisiae ProteinsAnimalsCatalytic DomainCryptococcus neoformansCyclic AMP-Dependent Protein KinasesGTP-Binding Protein alpha Subunits, Gq-G11Heterotrimeric GTP-Binding ProteinsMelaninsMiceMice, Inbred BALB CMutagenesisRabbitsVirulenceCyclic AMP-Dependent Protein KinasesGPA1 protein, S cerevisiaeGTP-Binding Protein alpha SubunitsGTP-Binding Protein alpha Subunits, Gq-G11Heterotrimeric GTP-Binding ProteinsMelaninsSaccharomyces cerevisiae Proteins

Identifiers

PMID11287622
PMCPMC86952
OpenAlexW2167737387

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.