Evidence map›Paper›PMID 11157776›Full record

ArticleGenes & development2001

Roles for inositol-phosphoryl ceramide synthase 1 (IPC1) in pathogenesis of C. neoformans.

C Luberto, D L Toffaletti, E A Wills, S C Tucker, A Casadevall, J R Perfect, Y A Hannun, M Del Poeta

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
–field-weighted citation impact
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

84 citing papers in PubMed, 151 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. bioRxiv : the preprint server for biology · 2025
    Article
  5. Article
  6. Role of sphingolipids in the host-pathogen interaction.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Two new sphingolipids from the stem bark ofBiochemistry and biophysics reports · 2021
    Article
  13. Review
  14. Review
  15. Mass Spectrometric Analysis of Bioactive Sphingolipids in Fungi.Methods in molecular biology (Clifton, N.J.) · 2021
    Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Article

24 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 1 country.

C LubertoDepartment of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
D L Toffaletti
E A Wills
S C Tucker
A Casadevall
J R Perfect
Y A Hannun
M Del Poeta
Duke University Hospital · USDuke Medical Center · USMedical University of South Carolina · US

Funding

Synergy of Host Defense Mechanisms in the LungR01HL059842 · NHLBI · YESHIVA UNIVERSITY · PI CASADEVALL, ARTURO · 1997 to 2023
$7.4M
Sphingomyelin Turnover and Cellular RegulationR37GM043825 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI HANNUN, YUSUF AWNI · 2007 to 2015
$3.7M
SIGNAL TRANSDUCTION PATHWAYS REGULATING VIRULENCEP01AI044975 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 1999 to 2003
$3.4M
SPHINGOMYELIN TURNOVER AND CELLULAR REGULATIONR01GM043825 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HANNUN, YUSUF AWNI · 1991 to 2006
$2.2M
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
NHLBI NIH HHS R01 HL059842NIAID NIH HHS AI28388NIAID NIH HHS AI44975NIAID NIH HHS P01 AI044975NIAID NIH HHS R01 AI028388NIAID NIH HHS R56 AI028388NIGMS NIH HHS GM 43825NIGMS NIH HHS R01 GM043825NIGMS NIH HHS R37 GM043825
6 · The paper itself

Abstract

Cryptococcus neoformans is a leading cause of life-threatening fungal infection in immunocompromised patients. Inositol-phosphoryl ceramide synthase 1 (Ipc1) is a fungus-specific enzyme, encoded by the essential IPC1 gene, that catalyzes the formation of complex sphingolipids and may also regulate the levels of phytoceramide and diacylglycerol. Here, we investigated the functions of this essential gene by modulating its expression in C. neoformans using a galactose-inducible promoter. Down-regulation of IPC1 significantly lowers the expression of certain virulence traits such as melanin pigmentation and, remarkably, impairs pathogenicity of C. neoformans in an established rabbit model. Interestingly, we found that IPC1 down-regulation significantly decreases the intracellular growth of C. neoformans in the J774.16 murine macrophage-like cells. Finally, we studied the effect of IPC1 expression under different stress conditions and found that down-regulation of IPC1 confers a defect on in vitro growth at low pH. Because this environment is similar to that in the phagolysosome of J774.16 macrophage-like cells, our findings indicate that down-regulation of IPC1 confers a growth defect in vivo through a pH-dependent mechanism. In conclusion, our study is the first to define a novel and crucial function of Ipc1 in fungal pathogenesis.

Indexed as

AnimalsBase SequenceCell LineCloning, MolecularCryptococcus neoformansDNA PrimersDown-RegulationGene Expression Regulation, EnzymologicGene Expression Regulation, FungalGenes, FungalHumansHydrogen-Ion ConcentrationMacrophagesMelaninsMiceOxidoreductasesdihydroceramide desaturaseDNA PrimersMelaninsOxidoreductases

Identifiers

PMID11157776
PMCPMC312614
OpenAlexW2046208000

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.