Evidence map›Paper›PMID 21652778›Full record

ArticlemBio2011

Cryptococcus neoformans requires a functional glycolytic pathway for disease but not persistence in the host.

Michael S Price, Marisol Betancourt-Quiroz, Jennifer L Price, Dena L Toffaletti, Haily Vora, Guanggan Hu, James W Kronstad, John R Perfect

Open access · goldAbstract read
In one paragraph

Article in mBio, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
7.2field-weighted citation impact, top 2% 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

75 citing papers in PubMed, 111 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Cryptococcal nutrient acquisition and pathogenesis: dining on the host.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Pleiotropic roles of LAMMER kinase, Lkh1 in stress responses and virulence ofFrontiers in cellular and infection microbiology · 2024
    Article
  18. Article
  19. Article
  20. Article

15 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

8 authors at 3 institutions in 2 countries.

Michael S PriceDepartment of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
Marisol Betancourt-Quiroz
Jennifer L Price
Dena L Toffaletti
Haily Vora
Guanggan Hu
James W Kronstad
John R Perfect
Duke Medical Center · USCanada's Michael Smith Genome Sciences Centre · CAUniversity of British Columbia · CA

Funding

Pathobiology of C. neoformans in the Central Nervous SystemR01AI073896 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 2008 to 2018
$4.4M
GENTIC &MOLECULAR BIOLOGY OF VIRULENCE IN C. NEOFORMANSR01AI028388 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 1991 to 2004
$1.9M
Genetic molecular biology of virulence in C. neoformansR56AI028388 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 2006 to 2006
$389k
NIAID NIH HHS R01 AI028388NIAID NIH HHS R01 AI073896NIAID NIH HHS R56 AI028388
6 · The paper itself

Abstract

Cryptococcus neoformans is an important fungal pathogen of immunocompromised individuals, with a close relative, Cryptococcus gattii, emerging as a serious threat for the immunocompetent. During initial infection, C. neoformans colonizes the airspaces of the lungs, resulting in pneumonia, and subsequently migrates to the central nervous system (CNS). We sought to understand fungal carbon utilization during colonization of these fundamentally different niches within the host, in particular the roles of gluconeogenesis and glycolysis. We created mutants at key points in the gluconeogenesis/glycolysis metabolic pathways that are restricted for growth on lactate and glucose, respectively. A phosphoenolpyruvate carboxykinase mutant (the pck1Δ mutant), blocked for entry of 2- and 3-carbon substrates into gluconeogenesis and attenuated for virulence in a murine inhalation model, showed wild-type (WT) persistence in a rabbit cerebrospinal fluid (CSF) model of cryptococcosis. Conversely, both the pyruvate kinase (pyk1Δ) and the hexose kinase I and II (hxk1Δ/hxk2Δ) mutants, which show impaired glucose utilization, exhibited severely attenuated virulence in the murine inhalation model of cryptococcosis and decreased persistence in the CNS in both the rabbit CSF and the murine inhalation models while displaying adequate persistence in the lungs of mice. These data suggest that glucose utilization is critical for virulence of C. neoformans and persistence of the yeast in the CNS.

Indexed as

GlycolysisAnimalsCryptococcosisCryptococcus neoformansDisease Models, AnimalFemaleGene DeletionGenes, FungalGluconeogenesisGlucoseHumansLactic AcidMaleMiceRabbitsRodent DiseasesGlucoseLactic AcidVirulence Factors

Identifiers

PMID21652778
PMCPMC3110414
OpenAlexW2156654507

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.