ArticleCellular and molecular life sciences : CMLS2020
Leishmania heme uptake involves LmFLVCRb, a novel porphyrin transporter essential for the parasite.
Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- Heme limitation induces LHR2, an essential gene for Leishmania pathogenesis.PLoS pathogens · 2026Article
- 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
- TransLeish: Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen.Nature communications · 2025Article
- Heme metabolism in Strigomonas culicis: Implications of HThe Journal of biological chemistry · 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
- Genetic Iron Overload Hampers Development of Cutaneous Leishmaniasis in Mice.International journal of molecular sciences · 2023Article
- New Insights on Heme Uptake inInternational journal of molecular sciences · 2022Article
- Identification and characterization of a heme exporter from the MRP family in Drosophila melanogaster.BMC biology · 2022Article
- Hemoglobin Endocytosis and Intracellular Trafficking: A Novel Way of Heme Acquisition byPathogens (Basel, Switzerland) · 2022Review
- Reporter gene systems: A powerful tool forCurrent research in microbial sciences · 2022Article
- Haem-responsive gene transporter enables mobilization of host haem in ticks.Open biology · 2021Article
- A new model forThe Journal of biological chemistry · 2020Article
- Porphyrin Derivative Nanoformulations for Therapy and Antiparasitic Agents.Molecules (Basel, Switzerland) · 2020Review
- Iron and Heme Metabolism at the Leishmania-Host Interface.Trends in parasitology · 2020Review
- Vitamin and cofactor acquisition in apicomplexans: SynthesisThe Journal of biological chemistry · 2020Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Leishmaniasis comprises a group of neglected diseases caused by the protozoan parasite Leishmania spp. As is the case for other trypanosomatid parasites, Leishmania is auxotrophic for heme and must scavenge this essential compound from its human host. In mammals, the SLC transporter FLVCR2 mediates heme import across the plasma membrane. Herein we identify and characterize Leishmania major FLVCRb (LmFLVCRb), the first member of the FLVCR family studied in a non-metazoan organism. This protein localizes to the plasma membrane of the parasite and is able to bind heme. LmFLVCRb levels in Leishmania, which are modulated by overexpression thereof or the abrogation of an LmFLVCRb allele, correlate with the ability of the parasite to take up porphyrins. Moreover, injection of LmFLVCRb cRNA to Xenopus laevis oocytes provides these cells with the ability to take up heme. This process is temperature dependent, requires monovalent ions and is inhibited at basic pH, characteristics shared by the uptake of heme by Leishmania parasites. Interestingly, LmFLVCRb is essential as CRISPR/Cas9-mediated knockout parasites were only obtained in the presence of an episomal copy of the gene. In addition, deletion of just one of the alleles of the LmFLVCRb gene markedly impairs parasite replication as intracellular amastigotes as well as its virulence in an in vivo model of cutaneous leishmaniasis. Collectively, these results show that Leishmania parasites can rescue heme through plasma membrane transporter LFLVCRb, which could constitute a novel target for therapeutic intervention against Leishmania and probably other trypanosomatid parasites in which FLVCR genes are also present.
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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.