Sodium-dependent uptake of inorganic phosphate by the intracellular malaria parasite

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. The parasite cytosol has a relatively low Na⁺ concentration 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.