ArticleInfection and immunity2013
Heme uptake mediated by LHR1 is essential for Leishmania amazonensis virulence.
Article in Infection and immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 66 citations in OpenAlex.
- Antileishmanial activity of gold(I) compounds containing triphenylphosphine ligands against Leishmania amazonensis: impacts on mitochondrial bioenergetics and trypanothione reductase activity.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- Heme limitation induces LHR2, an essential gene for Leishmania pathogenesis.PLoS pathogens · 2026Article
- Review
- Agreement Document for the Study of Leishmaniasis from a One Health Approach in Spain.Tropical medicine and infectious disease · 2025Article
- Heme and immunity: The heme oxygenase dichotomy.Journal of inorganic biochemistry · 2025Review
- Article
- Trypanosoma cruzi heme responsive gene (TcHRG) plays a central role in orchestrating heme uptake in epimastigotes.The FEBS journal · 2024Article
- In silico prediction of the metabolism of Blastocrithidia nonstop, a trypanosomatid with non-canonical genetic code.BMC genomics · 2024Article
- Targeting and activation of macrophages in leishmaniasis. A focus on iron oxide nanoparticles.Frontiers in immunology · 2024Review
- Access and utilization of host-derived iron by Leishmania parasites.Journal of biochemistry · 2023Review
- Notes from the Underground: Heme Homeostasis inBiomolecules · 2023Review
- Hemoglobin uptake and utilization by human protozoan parasites: a review.Frontiers in cellular and infection microbiology · 2023Review
- Antileishmanial Anthracene Endoperoxides: Efficacy In Vitro, Mechanisms and Structure-Activity Relationships.Molecules (Basel, Switzerland) · 2022Article
- New Insights on Heme Uptake inInternational journal of molecular sciences · 2022Article
- Characterization ofParasitology · 2022Article
- Article
- Hemoglobin Endocytosis and Intracellular Trafficking: A Novel Way of Heme Acquisition byPathogens (Basel, Switzerland) · 2022Review
- Causative Agents of American Tegumentary Leishmaniasis Are Able to Infect 3T3-L1 AdipocytesFrontiers in cellular and infection microbiology · 2022Article
- Haem-responsive gene transporter enables mobilization of host haem in ticks.Open biology · 2021Article
- A new model forThe Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The protozoan parasite Leishmania amazonensis is a heme auxotroph and must acquire this essential factor from the environment. Previous studies showed that L. amazonensis incorporates heme through the transmembrane protein LHR1 (Leishmania Heme Response 1). LHR1-null promastigotes were not viable, suggesting that the transporter is essential for survival. Here, we compared the growth, differentiation, and infectivity for macrophages and mice of wild-type, LHR1-single-knockout (LHR1/Δlhr1), and LHR1-complemented (LHR1/Δlhr1 plus LHR1) L. amazonensis strains. LHR1/Δlhr1 promastigotes replicated poorly in heme-deficient media and had lower intracellular heme content than wild-type parasites. LHR1/Δlhr1 promastigotes were also less effective in reducing ferric iron to ferrous iron, a reaction mediated by the heme-containing parasite enzyme LFR1 (Leishmania Ferric Reductase 1). LHR1/Δlhr1 parasites differentiated normally into aflagellated forms expressing amastigote-specific markers but were not able to replicate intracellularly after infecting macrophages. Importantly, the intracellular growth of LHR1/Δlhr1 amastigotes was fully restored when macrophages were allowed to phagocytose red blood cells prior to infection. LHR1/Δlhr1 parasites were also severely defective in the development of cutaneous lesions in mice. All phenotypes observed in LHR1/Δlhr1 L. amazonensis were rescued by expression of episomal LHR1. Our results reveal the importance of efficient heme uptake for L. amazonensis replication and vertebrate host infectivity, reinforcing the potential usefulness of LHR1 as a target for new antileishmanial drugs.
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Registered trials
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.