Evidence map›Paper›PMID 28061020›Full record

ArticleCellular microbiology2017

A P4-ATPase subunit of the Cdc50 family plays a role in iron acquisition and virulence in Cryptococcus neoformans.

Guanggan Hu, Mélissa Caza, Erik Bakkeren, Matthias Kretschmer, Gaurav Bairwa, Ethan Reiner, James Kronstad

Open access · bronzeAbstract read
In one paragraph

Article in Cellular microbiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

31 citing papers in PubMed, 33 citations in OpenAlex.

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  9. Review
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  11. Review
  12. Loss of Opi3 causes a lipid imbalance that influences the virulence traits ofFrontiers in cellular and infection microbiology · 2024
    Article
  13. Aneuploidy underlies brefeldin A-induced antifungal drug resistance inFrontiers in cellular and infection microbiology · 2024
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Heme sensing and trafficking in fungi.Fungal biology reviews · 2023
    Article
  19. Functional Analysis of the P-Type ATPases Apt2-4 fromJournal of fungi (Basel, Switzerland) · 2023
    Article
  20. Article
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

7 authors at 2 institutions in 1 country.

Guanggan HuMichael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
Mélissa CazaMichael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
Erik BakkerenMichael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
Matthias KretschmerMichael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
Gaurav BairwaMichael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
Ethan ReinerMichael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
James KronstadMichael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
Canada's Michael Smith Genome Sciences Centre · CAUniversity of British Columbia · CA

Funding

Comparative and functional genomics of C. neoformansR01AI053721 · NIAID · UNIVERSITY OF BRITISH COLUMBIA · PI KRONSTAD, JAMES W · 2003 to 2024
$5.4M
CIHRNIAID NIH HHS R01 AI053721
6 · The paper itself

Abstract

The pathogenic fungus Cryptococcus neoformans delivers virulence factors such as capsule polysaccharide to the cell surface to cause disease in vertebrate hosts. In this study, we screened for mutants sensitive to the secretion inhibitor brefeldin A to identify secretory pathway components that contribute to virulence. We identified an ortholog of the cell division control protein 50 (Cdc50) family of the noncatalytic subunit of type IV P-type ATPases (flippases) that establish phospholipid asymmetry in membranes and function in vesicle-mediated trafficking. We found that a cdc50 mutant in C. neoformans was defective for survival in macrophages, attenuated for virulence in mice and impaired in iron acquisition. The mutant also showed increased sensitivity to drugs associated with phospholipid metabolism (cinnamycin and miltefosine), the antifungal drug fluconazole and curcumin, an iron chelator that accumulates in the endoplasmic reticulum. Cdc50 is expected to function with catalytic subunits of flippases, and we previously documented the involvement of the flippase aminophospholipid translocases (Apt1) in virulence factor delivery. A comparison of phenotypes with mutants defective in genes encoding candidate flippases (designated APT1, APT2, APT3, and APT4) revealed similarities primarily between cdc50 and apt1 suggesting a potential functional interaction. Overall, these results highlight the importance of membrane composition and homeostasis for the ability of C. neoformans to cause disease.

Indexed as

AnimalsAntifungal AgentsBacteriocinsBrefeldin ACell DivisionCell MembraneCryptococcosisCryptococcus neoformansCurcuminEndoplasmic ReticulumFemaleFluconazoleFungal PolysaccharidesFungal ProteinsIronMacrophagesAntifungal AgentsBacteriocinsBrefeldin ACdc50 protein, Cryptococcus neoformanscinnamycinCurcuminFluconazoleFungal PolysaccharidesFungal ProteinsIronmiltefosinePeptides, CyclicPhospholipid Transfer ProteinsPhosphorylcholineP-type ATPasesVirulence Factorsantifungal drugcurcuminflippasehemepathogenesissecretionvein-type ore

Identifiers

PMID28061020
PMCPMC5429215
OpenAlexW2570921660

What OpenQuestion holds

Textmetadata
LicenceTDM
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.