Evidence map›Paper›PMID 18699866›Full record

ArticleMolecular microbiology2008

The Histoplasma capsulatum vacuolar ATPase is required for iron homeostasis, intracellular replication in macrophages and virulence in a murine model of histoplasmosis.

Jeremy Hilty, A George Smulian, Simon L Newman

Open access · bronzeAbstract read
In one paragraph

Article in Molecular microbiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

34 citing papers in PubMed, 53 citations in OpenAlex.

  1. Interactions BetweenMicroorganisms · 2026
    Article
  2. The Vacuolar Protein 8 (Vac8) Homolog inJournal of fungi (Basel, Switzerland) · 2025
    Article
  3. Genotypic diversity, virulence, and molecular genetic tools inMicrobiology and molecular biology reviews : MMBR · 2024
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Journal of fungi (Basel, Switzerland) · 2019
    Review
  10. Article
  11. Article
  12. Metals in fungal virulence.FEMS microbiology reviews · 2018
    Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
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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

3 authors at 2 institutions in 1 country.

Jeremy HiltyDepartment of Internal Medicine, Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
A George Smulian
Simon L Newman
Office of Infectious Diseases · USUniversity of Cincinnati Medical Center · US

Funding

Reactivation HistoplasmosisP01AI061298 · NIAID · UNIVERSITY OF CINCINNATI · PI NEWMAN, SIMON L. · 2004 to 2008
$3.8M
Interaction of H. capsulatum with Dendritic CellsR01AI049358 · NIAID · UNIVERSITY OF CINCINNATI · PI NEWMAN, SIMON L. · 2002 to 2006
$1.7M
NIAID NIH HHS AI-49358NIAID NIH HHS AI-61298NIAID NIH HHS P01 AI061298NIAID NIH HHS R01 AI049358
6 · The paper itself

Abstract

Histoplasma capsulatum is a dimorphic fungal pathogen that survives and replicates within macrophages (Mphi). To identify specific genes required for intracellular survival, we utilized Agrobacterium tumefaciens-mediated mutagenesis, and screened for H. capsulatum insertional mutants that were unable to survive in human Mphi. One colony was identified that had an insertion within VMA1, the catalytic subunit A of the vacuolar ATPase (V-ATPase). The vma1 mutant (vma1::HPH) grew normally on iron-replete medium, but not on iron-deficient media. On iron-deficient medium, the growth of the vma1 mutant was restored in the presence of wild-type (WT) H. capsulatum yeasts, or the hydroxamate siderophore, rhodotorulic acid. However, the inability to replicate within Mphi was only partially restored by the addition of exogenous iron. The vma1::HPH mutant also did not grow as a mold at 28 degrees C. Complementation of the mutant (vma/VMA1) restored its ability to replicate in Mphi, grow on iron-poor medium and grow as a mold at 28 degrees C. The vma1::HPH mutant was avirulent in a mouse model of histoplasmosis, whereas the vma1/VMA1 strain was as pathogenic as WT yeasts. These studies demonstrate the importance of V-ATPase function in the pathogenicity of H. capsulatum, in iron homeostasis and in fungal dimorphism.

Indexed as

Agrobacterium tumefaciensAnimalsDNA, FungalFungal ProteinsGenes, FungalGenetic Complementation TestHistoplasmaHistoplasmosisHomeostasisHumansIronLung Diseases, FungalMacrophagesMaleMiceMice, Inbred C57BLDNA, FungalFungal ProteinsIronSiderophoresVacuolar Proton-Translocating ATPases

Identifiers

PMID18699866
PMCPMC2570752
OpenAlexW1828201172

What OpenQuestion holds

Textmetadata
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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.