A comprehensive model of purine uptake by the malaria parasite Plasmodium falciparum: identification of four purine transport activities in intraerythrocytic parasites

Neils B. Quashie , Dominique Dorin-Semblat , Patrick G. Bray , Giancarlo A. Biagini , Christian Doerig , Lisa C. Ranford-Cartwright , Harry P. de Koning (1)

1 Institute of Biomedical and Life Sciences

Plasmodium falciparum is incapable of de novo purine biosynthesis, and is absolutely dependent on transporters to salvage purines from the environment. Only one low-affinity adenosine transporter has been characterised to date. Here we report a comprehensive study of purine nucleobase and nucleoside transport by intraerythrocytic P. falciparum parasites. Isolated trophozoites expressed (a) a high affinity hypoxanthine transporter with a secondary capacity for purine nucleosides, (b) a separate high affinity transporter for adenine (c) a low affinity adenosine transporter and (d) a low affinity/high capacity adenine carrier. Hypoxanthine was taken up with 12-fold higher efficiency than adenosine. Using a parasite clone with a disrupted PfNT1 gene we found that the high affinity hypoxanthine/nucleoside transport activity was completely abolished whereas the low affinity adenosine transport activity was unchanged. Adenine transport was increased, presumably to partly compensate for the loss of the high affinity hypoxanthine transporter. We thus propose a model for purine salvage in P. falciparum, based on the highly efficient uptake of hypoxanthine by PfNT1 and a high capacity for purine nucleoside uptake by a lower affinity carrier.

Mots clés: Life Sciences

Neils B. Quashie, Dominique Dorin-Semblat, Patrick G. Bray, Giancarlo A. Biagini, Christian Doerig, et al.. A comprehensive model of purine uptake by the malaria parasite Plasmodium falciparum: identification of four purine transport activities in intraerythrocytic parasites. Biochemical Journal, 2008, 411 (2), pp.287-295. ⟨10.1042/BJ20071460⟩. ⟨hal-00478901⟩