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

Ksenija Slavic; Sanjeev Krishna; Aparajita Lahree; Guillaume Bouyer; Kirsten K Hanson; Iset Vera; Jon K Pittman; Henry M Staines; Maria M Mota

doi:10.1038/ncomms10403

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

Ksenija Slavic, Sanjeev Krishna, Aparajita Lahree, Guillaume Bouyer, Kirsten K Hanson, Iset Vera, Jon K Pittman, Henry M Staines, Maria M Mota

Research output: Contribution to journal › Article › peer-review

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 Fe(2+) 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.

Original language	English
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10403
Publication status	Published - 20 Jan 2016

Research Beacons, Institutes and Platforms

Dalton Nuclear Institute

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ncomms10403

Cite this

@article{319cac1a20aa4fe4b759a153bf406f46,

title = "A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium.",

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 Fe(2+) 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.",

author = "Ksenija Slavic and Sanjeev Krishna and Aparajita Lahree and Guillaume Bouyer and Hanson, {Kirsten K} and Iset Vera and Pittman, {Jon K} and Staines, {Henry M} and Mota, {Maria M}",

year = "2016",

month = jan,

day = "20",

doi = "10.1038/ncomms10403",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Springer Nature",

}

TY - JOUR

T1 - A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium.

AU - Slavic, Ksenija

AU - Krishna, Sanjeev

AU - Lahree, Aparajita

AU - Bouyer, Guillaume

AU - Hanson, Kirsten K

AU - Vera, Iset

AU - Pittman, Jon K

AU - Staines, Henry M

AU - Mota, Maria M

PY - 2016/1/20

Y1 - 2016/1/20

N2 - 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 Fe(2+) 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.

AB - 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 Fe(2+) 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.

U2 - 10.1038/ncomms10403

DO - 10.1038/ncomms10403

M3 - Article

C2 - 26786069

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

ER -

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

Abstract

Research Beacons, Institutes and Platforms

UN SDGs

Access to Document

Fingerprint

Cite this