Evidence map›Paper›PMID 9882657›Full record

ArticleJournal of bacteriology1999

A glucan synthase FKS1 homolog in cryptococcus neoformans is single copy and encodes an essential function.

J R Thompson, C M Douglas, W Li, C K Jue, B Pramanik, X Yuan, T H Rude, D L Toffaletti, J R Perfect, M Kurtz

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Journal of bacteriology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 1 pooled it
8.2field-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

87 citing papers in PubMed, 1 synthesis or guideline pooled it, 195 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Mitochondrial cardiolipin sequestration of caspofungin underliesbioRxiv : the preprint server for biology · 2026
    Article
  5. Review
  6. Article
  7. Genomic Characterization ofVeterinary sciences · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. A fungal protein organizes both glycogen and cell wall glucans.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Review
  16. Pleiotropic roles of LAMMER kinase, Lkh1 in stress responses and virulence ofFrontiers in cellular and infection microbiology · 2024
    Article
  17. Aneuploidy underlies brefeldin A-induced antifungal drug resistance inFrontiers in cellular and infection microbiology · 2024
    Article
  18. Review
  19. Article
  20. Article

27 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

10 authors at 3 institutions in 1 country.

J R ThompsonInfectious Diseases, Merck Research Laboratories, Rahway, New Jersey 07065, USA. john_thompson@merck.com
C M Douglas
W Li
C K Jue
B Pramanik
X Yuan
T H Rude
D L Toffaletti
J R Perfect
M Kurtz
Merck & Co., Inc., Rahway, NJ, USA (United States) · USDuke Medical Center · USDuke University Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cryptococcal meningitis is a fungal infection, caused by Cryptococcus neoformans, which is prevalent in immunocompromised patient populations. Treatment failures of this disease are emerging in the clinic, usually associated with long-term treatment with existing antifungal agents. The fungal cell wall is an attractive target for drug therapy because the syntheses of cell wall glucan and chitin are processes that are absent in mammalian cells. Echinocandins comprise a class of lipopeptide compounds known to inhibit 1,3-beta-glucan synthesis, and at least two compounds belonging to this class are currently in clinical trials as therapy for life-threatening fungal infections. Studies of Saccharomyces cerevisiae and Candida albicans mutants identify the membrane-spanning subunit of glucan synthase, encoded by the FKS genes, as the molecular target of echinocandins. In vitro, the echinocandins show potent antifungal activity against Candida and Aspergillus species but are much less potent against C. neoformans. In order to examine why C. neoformans cells are less susceptible to echinocandin treatment, we have cloned a homolog of S. cerevisiae FKS1 from C. neoformans. We have developed a generalized method to evaluate the essentiality of genes in Cryptococcus and applied it to the FKS1 gene. The method relies on homologous integrative transformation with a plasmid that can integrate in two orientations, only one of which will disrupt the target gene function. The results of this analysis suggest that the C. neoformans FKS1 gene is essential for viability. The C. neoformans FKS1 sequence is closely related to the FKS1 sequences from other fungal species and appears to be single copy in C. neoformans. Furthermore, amino acid residues known to be critical for echinocandin susceptibility in Saccharomyces are conserved in the C. neoformans FKS1 sequence.

Indexed as

Saccharomyces cerevisiae ProteinsSchizosaccharomyces pombe ProteinsAmino Acid SequenceCell WallCloning, MolecularConsensus SequenceCryptococcus neoformansDNA, FungalDNA PrimersEchinocandinsEnzyme InhibitorsFungal ProteinsGenes, EssentialGenes, FungalGlucosyltransferasesHumans1,3-beta-glucan synthaseDNA, FungalDNA PrimersEchinocandinsEnzyme InhibitorsFKS1 protein, S cerevisiaeFungal ProteinsGlucosyltransferasesMembrane ProteinsSaccharomyces cerevisiae ProteinsSchizosaccharomyces pombe Proteins

Identifiers

PMID9882657
PMCPMC93397
OpenAlexW2156187403

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.