Malaria is one of the most deadly infectious diseases that affects humans. Its most severe form, caused by the protozoan parasite Plasmodium falciparum, is transmitted to people by mosquitoes. The parasite has many life-cycle stages, and during the stage when the parasite is free in the human blood stream it invades red blood cells (erythrocytes), where it reproduces asexually. Parasites are dependent on erythrocytes for all their nutrients and one key question scientists want to answer is how a parasite obtains nutrients after it has settled inside its host blood cell. In a recent Naturearticle Stefan Bröer, Kiaran Kirk and co-workers from the Universities of Canberra and Melbourne, Australia, provide an interesting insight into this question. They show that parasites exploit the high sodium (Na+)levels that they induce in infected erythrocytes to drive the uptake of inorganic phosphate (Pi), an essential nutrient that is required to synthesise important molecules such as nucleic acids.

First the team confirmed that parasites need Pi. They monitored parasite growth in the presence and absence of Pi by measuring the rate at which radiolabeled DNA precursors were incorporated into newly synthesised DNA molecules. Parasites, still inside their host erythrocytes,stopped reproducing almost completely when the researchers removed Pi from their laboratory culture, showing that they need Pi to reproduce. This also suggested that they possess an uptake system to extract Pi from the erythrocyte's cytoplasm. To investigate the mechanism by which Pi is taken up, the scientists isolated the parasites from their host cells, placing them in another laboratory culture and measured them taking up radioactive 33Pi. They observed that the parasites took up forty times more 33Pi when there was Na+ in the extracellular medium. Replacing Na+ with either K+ or choline stopped Pi uptake almost completely, so the scientists concluded that Pi uptake involves a Na+-dependent transporter in the cell membrane.

Analysing the transport characteristics in closer detail indicated that the parasite takes up two Na+ ions with each Pi molecule. Since single negatively charged hydrogen phosphate turned out to be the preferred transport substrate, Pi uptake appears to be electrogenic, meaning that it is driven by an electric potential caused by an ion imbalance across the parasite's plasma membrane.

Next the researchers tracked down the gene coding the transporter. As the Plasmodium genome contains only a single gene for a plasma membrane Pi transporter, called PfPiT, the scientists suspected that this transporter could account for Pi uptake by the parasite. They discovered that PfPiT is found on the parasite's surface and is expressed throughout the entire blood stage of its life cycle, which supported their assumption that this transporter allows parasites to take up Pi. To provide final proof for PfPiT's supposed function in parasites, the team expressed the protein in Xenopus oocytes by injecting it's RNA. They measured the uptake of radioactive 33Pi in injected and non-injected oocytes, observing uptake of 33Pi in the eggs containing the parasite transporter RNA only, which was clearly caused by PfPiT expression.

The researchers think that the rise in Na+ levels in infected erythrocytes is vital for the parasites' survival as it means they can take up solutes such as Pivia Na+ dependent transporters. These results will help researchers understand further the malaria parasite's physiology and could pave the way for new strategies to combat malaria.

Saliba, K. J., Martin, R. E., Bröer, A., Henry, R. I.,McCarthy, C. S., Downie, M. J., Allen, R. J. W., Mullin, K. A., McFadden, G. I., Bröer, S. and Kirk, K. (
2006
). Sodium dependent uptake of inorganic phosphate by the intracellular malaria parasite.
Nature
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