Evidence map›Paper›PMID 25275454›Full record

ArticlePLoS pathogens2014

A relay network of extracellular heme-binding proteins drives C. albicans iron acquisition from hemoglobin.

Galit Kuznets, Elena Vigonsky, Ziva Weissman, Daniela Lalli, Tsvia Gildor, Sarah J Kauffman, Paola Turano, Jeffrey Becker, Oded Lewinson, Daniel Kornitzer

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
5.6field-weighted citation impact, top 3% 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

77 citing papers in PubMed, 117 citations in OpenAlex.

  1. Article
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  4. Genome-Wide Identification of CFEM Proteins inPlants (Basel, Switzerland) · 2026
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  5. Review
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  8. Deletion ofmSphere · 2025
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  10. Infection and immunity · 2025
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  11. Article
  12. Frontiers in cellular and infection microbiology · 2025
    Article
  13. Article
  14. International journal of molecular sciences · 2024
    Article
  15. The pathobiology of human fungal infections.Nature reviews. Microbiology · 2024
    Review
  16. Metals at the Host-Fungal Pathogen Battleground.Annual review of microbiology · 2024
    Review
  17. Article
  18. Article
  19. Article
  20. Article

17 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 3 countries.

Galit KuznetsB. Rappaport Faculty of Medicine, Technion - I.I.T. and the Rappaport Institute for Research in the Medical Sciences, Haifa, Israel.
Elena VigonskyB. Rappaport Faculty of Medicine, Technion - I.I.T. and the Rappaport Institute for Research in the Medical Sciences, Haifa, Israel.
Ziva WeissmanB. Rappaport Faculty of Medicine, Technion - I.I.T. and the Rappaport Institute for Research in the Medical Sciences, Haifa, Israel.
Daniela LalliCERM and Department of Chemistry, University of Florence, Sesto Fiorentino, Italy.
Tsvia GildorB. Rappaport Faculty of Medicine, Technion - I.I.T. and the Rappaport Institute for Research in the Medical Sciences, Haifa, Israel.
Sarah J KauffmanMicrobiology Department, University of Tennessee, Knoxville, Tennessee, United States of America.
Paola TuranoCERM and Department of Chemistry, University of Florence, Sesto Fiorentino, Italy.
Jeffrey BeckerMicrobiology Department, University of Tennessee, Knoxville, Tennessee, United States of America.
Oded LewinsonB. Rappaport Faculty of Medicine, Technion - I.I.T. and the Rappaport Institute for Research in the Medical Sciences, Haifa, Israel.
Daniel KornitzerB. Rappaport Faculty of Medicine, Technion - I.I.T. and the Rappaport Institute for Research in the Medical Sciences, Haifa, Israel.
Rappaport Family Institute for Research in the Medical Sciences · ILUniversity of Florence · ITUniversity of Tennessee at Knoxville · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Iron scavenging constitutes a crucial challenge for survival of pathogenic microorganisms in the iron-poor host environment. Candida albicans, like many microbial pathogens, is able to utilize iron from hemoglobin, the largest iron pool in the host's body. Rbt5 is an extracellular glycosylphosphatidylinositol (GPI)-anchored heme-binding protein of the CFEM family that facilitates heme-iron uptake by an unknown mechanism. Here, we characterize an additional C. albicans CFEM protein gene, PGA7, deletion of which elicits a more severe heme-iron utilization phenotype than deletion of RBT5. The virulence of the pga7-/- mutant is reduced in a mouse model of systemic infection, consistent with a requirement for heme-iron utilization for C. albicans pathogenicity. The Pga7 and Rbt5 proteins exhibit distinct cell wall attachment, and discrete localization within the cell envelope, with Rbt5 being more exposed than Pga7. Both proteins are shown here to efficiently extract heme from hemoglobin. Surprisingly, while Pga7 has a higher affinity for heme in vitro, we find that heme transfer can occur bi-directionally between Pga7 and Rbt5, supporting a model in which they cooperate in a heme-acquisition relay. Together, our data delineate the roles of Pga7 and Rbt5 in a cell surface protein network that transfers heme from extracellular hemoglobin to the endocytic pathway, and provide a paradigm for how receptors embedded in the cell wall matrix can mediate nutrient uptake across the fungal cell envelope.

Indexed as

AnimalsCandida albicansCarrier ProteinsCell WallExtracellular SpaceGlycosylphosphatidylinositolsHemeHeme-Binding ProteinsHemeproteinsHemoglobinsHumansIronMiceVirulenceCarrier ProteinsGlycosylphosphatidylinositolsHemeHeme-Binding ProteinsHemeproteinsHemoglobinsIron

Identifiers

PMID25275454
PMCPMC4183699
OpenAlexW2035894033

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.