Evidence map›Paper›PMID 26431038›Full record

ArticlePLoS pathogens2015

Disruption of Sphingolipid Biosynthesis Blocks Phagocytosis of Candida albicans.

Fikadu G Tafesse, Ali Rashidfarrokhi, Florian I Schmidt, Elizaveta Freinkman, Stephanie Dougan, Michael Dougan, Alexandre Esteban, Takeshi Maruyama, Karin Strijbis, Hidde L Ploegh

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

40 citing papers in PubMed, 76 citations in OpenAlex.

  1. Article
  2. A critical signaling role for diacylglycerol in phagocytosis ofbioRxiv : the preprint server for biology · 2026
    Article
  3. EditingBiomolecules · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. ThemBio · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
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  14. Article
  15. Article
  16. Review
  17. Article
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  20. Review
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

10 authors at 2 institutions in 1 country.

Fikadu G TafesseWhitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
Ali RashidfarrokhiWhitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
Florian I SchmidtWhitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Elizaveta FreinkmanWhitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Stephanie DouganWhitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Michael DouganWhitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Alexandre EstebanWhitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Takeshi MaruyamaWhitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Karin StrijbisWhitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Hidde L PloeghWhitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Massachusetts Institute of Technology · USWhitehead Institute for Biomedical Research · US

Funding

Sortase-mediated protein engineering for the study of host-pathogen interactionsR01AI087879 · NIAID · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI PLOEGH, HIDDE L. · 2010 to 2019
$4.5M
NIAID NIH HHS AI087879NIAID NIH HHS R01 AI087879
6 · The paper itself

Abstract

The ability of phagocytes to clear pathogens is an essential attribute of the innate immune response. The role of signaling lipid molecules such as phosphoinositides is well established, but the role of membrane sphingolipids in phagocytosis is largely unknown. Using a genetic approach and small molecule inhibitors, we show that phagocytosis of Candida albicans requires an intact sphingolipid biosynthetic pathway. Blockade of serine-palmitoyltransferase (SPT) and ceramide synthase-enzymes involved in sphingolipid biosynthesis- by myriocin and fumonisin B1, respectively, impaired phagocytosis by phagocytes. We used CRISPR/Cas9-mediated genome editing to generate Sptlc2-deficient DC2.4 dendritic cells, which lack serine palmitoyl transferase activity. Sptlc2-/- DC2.4 cells exhibited a stark defect in phagocytosis, were unable to bind fungal particles and failed to form a normal phagocytic cup to engulf C. albicans. Supplementing the growth media with GM1, the major ganglioside present at the cell surface, restored phagocytic activity of Sptlc2-/- DC2.4 cells. While overall membrane trafficking and endocytic pathways remained functional, Sptlc2-/- DC2.4 cells express reduced levels of the pattern recognition receptors Dectin-1 and TLR2 at the cell surface. Consistent with the in vitro data, compromised sphingolipid biosynthesis in mice sensitizes the animal to C. albicans infection. Sphingolipid biosynthesis is therefore critical for phagocytosis and in vivo clearance of C. albicans.

Indexed as

Candida albicansAnimalsCandidiasisCell LineChromatography, Thin LayerDendritic CellsDisease Models, AnimalFlow CytometryGene Knockout TechniquesHost-Pathogen InteractionsHumansMass SpectrometryMicePhagocytosisSphingolipidsSphingolipids

Identifiers

PMID26431038
PMCPMC4592247
OpenAlexW1873586050

What OpenQuestion holds

Textmetadata
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.