Parasite maturation and host serum iron influence the labile iron pool of erythrocyte stage Plasmodium falciparum

Authors

  • Martha Clark,

    1. Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, USA, United States
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  • Nancy C. Fisher,

    1. Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, USA, United States
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  • Raj Kasthuri,

    1. Department of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA
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  • Carla Cerami Hand

    Corresponding author
    1. Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA
    • Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, USA, United States
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Correspondence: Carla Cerami Hand, CB# 7345 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA. E-mail: cchand@email.unc.edu

Summary

Iron is a critical and tightly regulated nutrient for both the malaria parasite and its human host. The importance of the relationship between host iron and the parasite has been underscored recently by studies showing that host iron supplementation may increase the risk of falciparum malaria. It is unclear what host iron sources the parasite is able to access. We developed a flow cytometry-based method for measuring the labile iron pool (LIP) of parasitized erythrocytes using the nucleic acid dye STYO 61 and the iron sensitive dye, calcein acetoxymethyl ester (CA-AM). This new approach enabled us to measure the LIP of P. falciparum through the course of its erythrocytic life cycle and in response to the addition of host serum iron sources. We found that the LIP increases as the malaria parasite develops from early ring to late schizont stage, and that the addition of either transferrin or ferric citrate to culture media increases the LIP of trophozoites. Our method for detecting the LIP within malaria parasitized RBCs provides evidence that the parasite is able to access serum iron sources as part of the host vs. parasite arms race for iron.

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