Evidence map›Paper›PMID 23450261›Full record

ArticleG3 (Bethesda, Md.)2013

Calcineurin governs thermotolerance and virulence of Cryptococcus gattii.

Ying-Lien Chen, Virginia N Lehman, Yonathan Lewit, Anna F Averette, Joseph Heitman

Open access · goldAbstract read
In one paragraph

Article in G3 (Bethesda, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.5field-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

37 citing papers in PubMed, 57 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Roles of Different Signaling Pathways inJournal of fungi (Basel, Switzerland) · 2024
    Review
  5. Review
  6. Article
  7. Gene, virulence and related regulatory mechanisms inActa biochimica et biophysica Sinica · 2022
    Review
  8. FasterJournal of fungi (Basel, Switzerland) · 2022
    Article
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  11. Review
  12. Article
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  14. Article
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  16. Review
  17. Review
  18. 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 3 institutions in 2 countries.

Ying-Lien ChenDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Virginia N Lehman
Yonathan Lewit
Anna F Averette
Joseph Heitman
Duke University Hospital · USDuke Medical Center · USDuke University · US

Funding

Social and Behavioral Sciences CoreP30AI064518 · NIAID · DUKE UNIVERSITY · PI Nwora Lance Okeke · 2005 to 2026
$50.5M
Novel Antifungal Therapeutic ApproachesR01AI050438 · NIAID · DUKE UNIVERSITY · PI HEITMAN, JOSEPH · 2001 to 2012
$3.3M
NIAID NIH HHS 2P30 AI064518-06NIAID NIH HHS P30 AI064518NIAID NIH HHS R01 AI050438NIAID NIH HHS R01 AI50438
6 · The paper itself

Abstract

The pathogenic yeast Cryptococcus gattii, which is causing an outbreak in the Pacific Northwest region of North America, causes life-threatening pulmonary infections and meningoencephalitis in healthy individuals, unlike Cryptococcus neoformans, which commonly infects immunocompromised patients. In addition to a greater predilection for C. gattii to infect healthy hosts, the C. gattii genome sequence project revealed extensive chromosomal rearrangements compared with C. neoformans, showing genomic differences between the two Cryptococcus species. We investigated the roles of C. gattii calcineurin in three molecular types: VGIIa (R265), VGIIb (R272), and VGI (WM276). We found that calcineurin exhibits a differential requirement for growth on solid medium at 37°, as calcineurin mutants generated from R265 were more thermotolerant than mutants from R272 and WM276. We demonstrated that tolerance to calcineurin inhibitors (FK506, CsA) at 37° is linked with the VGIIa molecular type. The calcineurin mutants from the R272 background showed the most extensive growth and morphological defects (multivesicle and larger ring-like cells), as well as increased fluconazole susceptibility. Our cellular architecture examination showed that C. gattii and C. neoformans calcineurin mutants exhibit plasma membrane disruptions. Calcineurin in the C. gattii VGII molecular type plays a greater role in controlling cation homeostasis compared with that in C. gattii VGI and C. neoformans H99. Importantly, we demonstrate that C. gattii calcineurin is essential for virulence in a murine inhalation model, supporting C. gattii calcineurin as an attractive antifungal drug target.

Indexed as

Adaptation, PhysiologicalGenes, FungalAnimalsAntifungal AgentsBrainCalcineurinCell MembraneCryptococcus gattiiCulture MediaFemaleFluconazoleGene DeletionGenetic Complementation TestLarvaLungMiceAntifungal AgentsCalcineurinCulture MediaFluconazolecapsulecation homeostasiscyclosporin AFK506fluconazole tolerancemelaninpathogenicitytemperature sensitivity

Identifiers

PMID23450261
PMCPMC3583459
OpenAlexW2167620764

What OpenQuestion holds

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LicenceCC BY
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.