Evidence map›Paper›PMID 23382545›Full record

ArticleThe Journal of experimental medicine2013

Iron uptake controls the generation of Leishmania infective forms through regulation of ROS levels.

Bidyottam Mittra, Mauro Cortez, Andrew Haydock, Gowthaman Ramasamy, Peter J Myler, Norma W Andrews

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed, 1 pooled it
13.0field-weighted citation impact, top 1% 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

70 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Frontiers in immunology · 2026
    Review
  4. Article
  5. Heme and immunity: The heme oxygenase dichotomy.Journal of inorganic biochemistry · 2025
    Review
  6. Article
  7. Heme metabolism in Strigomonas culicis: Implications of HThe Journal of biological chemistry · 2024
    Article
  8. Article
  9. AnHeliyon · 2024
    Article
  10. Upregulation of ATP6V0D2 benefits intracellular survival ofFrontiers in cellular and infection microbiology · 2024
    Article
  11. Review
  12. Article
  13. Iron Uptake ControlsAntioxidants (Basel, Switzerland) · 2023
    Article
  14. Article
  15. Promastigote-to-Amastigote Conversion inPathogens (Basel, Switzerland) · 2022
    Review
  16. Review
  17. Article
  18. Catalase impairsVirulence · 2021
    Article
  19. Pathogens (Basel, Switzerland) · 2021
    Article
  20. Article

10 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

6 authors at 2 institutions in 1 country.

Bidyottam MittraDepartment of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Mauro Cortez
Andrew Haydock
Gowthaman Ramasamy
Peter J Myler
Norma W Andrews
Center for Infectious Disease Research · USUniversity of Maryland, College Park · US

Funding

Molecular Determinants of Intracellular Survival and Replication in LeishmaniaR01AI067979 · NIAID · YALE UNIVERSITY · PI ANDREWS, NORMA WINDSOR · 2007 to 2018
$3.8M
LYSOSOME-MEDIATED CELL INVASION BY TRYPANOSOMA CRUZIR01AI034867 · NIAID · YALE UNIVERSITY · PI ANDREWS, NORMA WINDSOR · 1994 to 2003
$880k
NIAID NIH HHS R01 AI034867NIAID NIH HHS R01 AI067979NIAID NIH HHS R01AI067979
6 · The paper itself

Abstract

During its life cycle, Leishmania undergoes extreme environmental changes, alternating between insect vectors and vertebrate hosts. Elevated temperature and decreased pH, conditions encountered after macrophage invasion, can induce axenic differentiation of avirulent promastigotes into virulent amastigotes. Here we show that iron uptake is a major trigger for the differentiation of Leishmania amazonensis amastigotes, independently of temperature and pH changes. We found that iron depletion from the culture medium triggered expression of the ferrous iron transporter LIT1 (Leishmania iron transporter 1), an increase in iron content of the parasites, growth arrest, and differentiation of wild-type (WT) promastigotes into infective amastigotes. In contrast, LIT1-null promastigotes showed reduced intracellular iron content and sustained growth in iron-poor media, followed by cell death. LIT1 up-regulation also increased iron superoxide dismutase (FeSOD) activity in WT but not in LIT1-null parasites. Notably, the superoxide-generating drug menadione or H(2)O(2) was sufficient to trigger differentiation of WT promastigotes into fully infective amastigotes. LIT1-null promastigotes accumulated superoxide radicals and initiated amastigote differentiation after exposure to H(2)O(2) but not to menadione. Our results reveal a novel role for FeSOD activity and reactive oxygen species in orchestrating the differentiation of virulent Leishmania amastigotes in a process regulated by iron availability.

Indexed as

AnimalsBase SequenceBiological Transport, ActiveCation Transport ProteinsFemaleGenes, ProtozoanHost-Parasite InteractionsHumansIronLeishmania mexicanaLeishmaniasis, CutaneousMacrophagesMiceMice, Inbred BALB CProtozoan ProteinsReactive Oxygen SpeciesCation Transport ProteinsIronProtozoan ProteinsReactive Oxygen SpeciesRNA, ProtozoanSuperoxide Dismutase

Identifiers

PMID23382545
PMCPMC3570109
OpenAlexW2096153302

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.