Evidence map›Paper›PMID 12933823›Full record

ArticleInfection and immunity2003

Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates.

Kirsten Nielsen, Gary M Cox, Ping Wang, Dena L Toffaletti, John R Perfect, Joseph Heitman

Open access · greenAbstract read
In one paragraph

Article in Infection and immunity, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 267 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
267citing papers in PubMed, 1 pooled it
10.8field-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

267 citing papers in PubMed, 1 synthesis or guideline pooled it, 401 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. TREM2 drives monocyte-derived macrophage responses tobioRxiv : the preprint server for biology · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Unisexual reproduction in the global human fungal pathogenbioRxiv : the preprint server for biology · 2025
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. The hypervirulent Type-1/Type-17 phenotype ofInfection and immunity · 2025
    Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Kirsten NielsenDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Gary M Cox
Ping Wang
Dena L Toffaletti
John R Perfect
Joseph Heitman
Duke Medical Center · USDuke University Hospital · US

Funding

Structure, function, and evolution of the Cryptococcus MAT locusR01AI050113 · NIAID · DUKE UNIVERSITY · PI HEITMAN, JOSEPH · 2002 to 2024
$8.5M
SIGNAL TRANSDUCTION PATHWAYS REGULATING VIRULENCEP01AI044975 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 1999 to 2003
$3.4M
GENTIC &MOLECULAR BIOLOGY OF VIRULENCE IN C. NEOFORMANSR01AI028388 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 1991 to 2004
$1.9M
NIAID NIH HHS AI44975NIAID NIH HHS AI50113NIAID NIH HHS P01 AI044975NIAID NIH HHS R01 AI028388NIAID NIH HHS R01 AI050113NIAID NIH HHS R01 AI28388
6 · The paper itself

Abstract

Cryptococcus neoformans is a human-pathogenic fungus that has evolved into three distinct varieties that infect most prominently the central nervous system. A sexual cycle involving haploid cells of a and alpha mating types has been reported for two varieties (C. neoformans var. neoformans, serotype D, and C. neoformans var. gattii, serotypes B and C), yet the vast majority of infections involve a distinct variety (C. neoformans var. grubii, serotype A) that has been thought to be clonal and restricted to the alpha mating type. We recently identified the first serotype A isolate of the a mating type which had been thought to be extinct (strain 125.91). Here we report that this unusual strain can mate with a subset of pathogenic serotype A strains to produce a filamentous dikaryon with fused clamp connections, basidia, and viable recombinant basidiospores. One meiotic segregant mated poorly with the serotype A reference strain H99 but robustly with a crg1 mutant that lacks a regulator of G protein signaling and is hyperresponsive to mating pheromone. This meiotic segregant was used to create congenic a and alpha mating type serotype A strains. Virulence tests with rabbit and murine models of cryptococcal meningitis showed that the serotype A congenic a and alpha mating type strains had equivalent virulence in animal models, in contrast to previous studies linking the alpha mating type to increased virulence in congenic serotype D strains. Our studies highlight a role for sexual recombination in the evolution of a human fungal pathogen and provide a robust genetic platform to establish the molecular determinants of virulence.

Indexed as

AnimalsBase SequenceCryptococcus neoformansDNA, FungalFemaleGenes, FungalGenes, Mating Type, FungalHaploidyHumansMaleMeningitis, CryptococcalMiceMice, Inbred AMolecular Sequence DataMutationOpportunistic InfectionsDNA, Fungal

Identifiers

PMID12933823
PMCPMC187335
OpenAlexW2120277859

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.