1. School of Biochemistry and Molecular Biology,
2. Medical School, The Australian National University, Canberra ACT 0200, Australia
3. School of Botany, University of Melbourne, Victoria 3010, Australia
4. *These authors contributed equally to this work

Correspondence to: Kiaran Kirk¹ Correspondence and requests for materials should be addressed to K.K. (Email: kiaran.kirk@anu.edu.au).

As the malaria parasite, Plasmodium falciparum, grows within its host erythrocyte it induces an increase in the permeability of the erythrocyte membrane to a range of low-molecular-mass solutes, including Na⁺ and K⁺ (ref. 1). This results in a progressive increase in the concentration of Na⁺ in the erythrocyte cytosol^{2, 3}. The parasite cytosol has a relatively low Na⁺ concentration^{2, 4} and there is therefore a large inward Na⁺ gradient across the parasite plasma membrane. Here we show that the parasite exploits the Na⁺ electrochemical gradient to energize the uptake of inorganic phosphate (P_i), an essential nutrient. P_i was taken up into the intracellular parasite by a Na⁺-dependent transporter, with a stoichiometry of 2Na⁺:1P_i and with an apparent preference for the monovalent over the divalent form of P_i. A P_i transporter (PfPiT) belonging to the PiT family was cloned from the parasite and localized to the parasite surface. Expression of PfPiT in Xenopus oocytes resulted in Na⁺-dependent P_i uptake with characteristics similar to those observed for P_i uptake in the parasite. This study provides new insight into the significance of the malaria-parasite-induced alteration of the ionic composition of its host cell.

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