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A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium

Author

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  • Ksenija Slavic

    (Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa)

  • Sanjeev Krishna

    (Institute for Infection & Immunity, St. George’s, University of London)

  • Aparajita Lahree

    (Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa)

  • Guillaume Bouyer

    (Institute for Infection & Immunity, St. George’s, University of London
    Sorbonne Universités, UPMC Univ Paris 6, CNRS, UMR 8227, Comparative Physiology of Erythrocytes, Station Biologique de Roscoff)

  • Kirsten K. Hanson

    (Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa
    Present address: University of Texas at San Antonio, Department of Biology and STCEID, San Antonio, Texas 78249, USA)

  • Iset Vera

    (Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa)

  • Jon K. Pittman

    (Faculty of Life Sciences, University of Manchester)

  • Henry M. Staines

    (Institute for Infection & Immunity, St. George’s, University of London)

  • Maria M. Mota

    (Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa)

Abstract

Iron is an essential micronutrient but is also highly toxic. In yeast and plant cells, a key detoxifying mechanism involves iron sequestration into intracellular storage compartments, mediated by members of the vacuolar iron-transporter (VIT) family of proteins. Here we study the VIT homologue from the malaria parasites Plasmodium falciparum (PfVIT) and Plasmodium berghei (PbVIT). PfVIT-mediated iron transport in a yeast heterologous expression system is saturable (Km∼14.7 μM), and selective for Fe2+ over other divalent cations. PbVIT-deficient P. berghei lines (Pbvit−) show a reduction in parasite load in both liver and blood stages of infection in mice. Moreover, Pbvit− parasites have higher levels of labile iron in blood stages and are more sensitive to increased iron levels in liver stages, when compared with wild-type parasites. Our data are consistent with Plasmodium VITs playing a major role in iron detoxification and, thus, normal development of malaria parasites in their mammalian host.

Suggested Citation

  • Ksenija Slavic & Sanjeev Krishna & Aparajita Lahree & Guillaume Bouyer & Kirsten K. Hanson & Iset Vera & Jon K. Pittman & Henry M. Staines & Maria M. Mota, 2016. "A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10403
    DOI: 10.1038/ncomms10403
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