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

Research output: Contribution to journalArticleResearchpeer-review

33 Citations (Scopus)

Abstract

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 characterized to date. In the present study we report a comprehensive study of purine nucleobase and nucleoside transport by intraerythrocytic P. falciparum parasites. Isolated trophozoites expressed (i) a high-affinity hypoxanthine transporter with a secondary capacity for purine nucleosides, (ii) a separate high-affinity transporter for adenine, (iii) a low-affinity adenosine transporter, and (iv) 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 (P. falciparum nucleoside transporter 1) 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.

Original languageEnglish
Pages (from-to)287-295
Number of pages9
JournalBiochemical Journal
Volume411
Issue number2
DOIs
Publication statusPublished - 15 Apr 2008
Externally publishedYes

Keywords

  • Drug target
  • Equilibrative nucleoside transporter family
  • Nucleobase transporter
  • PfNT1
  • Plasmodium falciparum
  • Purine salvage

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