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Published on: March 16, 2018
Heme as a source of iron to Leishmania infantum amastigotes
Sandra Carvalho1, Tânia Cruz, Nuno Santarém
1Instituto de Biologia Molecular e Celular, Porto, Portugal.
Abstract:
Amastigotes, the mammalian stage of Leishmania, must acquire iron from molecules accessing the macrophage parasitophorous vacuole (PV) where they inhabit. These molecules likely include non-heme and heme-bound forms of iron. Here we demonstrate that, in addition to the previously documented use of ferrous iron, Leishmania amastigotes are also capable of exploiting iron from hemin and hemoglobin for nutritional purposes. Moreover, evidence is presented that a ligand at the surface of amastigotes binds hemin with high-affinity (Kd=0.044nM). This ligand may function in intracellular transport of heme while hemoglobin internalization occurs through a different molecule. The co-existence in Leishmania amastigotes of different processes to acquire iron could constitute an infective strategy, ensuring parasites a substantial advantage in situations of iron limitation.
Insights
Leishmania parasites, the mammalian stage of Leishmania, can use hemin and hemoglobin for iron, not just ferrous iron. This dual iron acquisition strategy aids parasite survival during iron scarcity.
Area of Science:
- Parasitology
- Molecular Biology
- Infectious Diseases
Background:
- Leishmania amastigotes reside within macrophage parasitophorous vacuoles (PVs).
- Parasites require iron for survival and proliferation.
- Iron sources in the PV likely include heme and non-heme iron.
Purpose of the Study:
- To investigate Leishmania amastigote's ability to utilize hemin and hemoglobin as iron sources.
- To identify potential mechanisms for heme and hemoglobin uptake.
- To understand the role of iron acquisition in Leishmania infection.
Main Methods:
- Nutritional assays to assess iron utilization from hemin and hemoglobin.
- Binding studies to characterize the interaction between amastigote surface ligands and hemin.
- Comparative analysis of iron uptake pathways.
Main Results:
- Leishmania amastigotes effectively utilize iron from hemin and hemoglobin, in addition to ferrous iron.
- A high-affinity hemin-binding ligand (Kd=0.044nM) was identified on the amastigote surface.
- Evidence suggests distinct mechanisms for hemin and hemoglobin internalization.
Conclusions:
- Leishmania amastigotes possess multiple strategies for iron acquisition, including heme and hemoglobin.
- A specific surface ligand facilitates hemin uptake.
- These adaptable iron acquisition mechanisms likely enhance parasite infectivity and survival under iron-limited conditions.
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