The plasma membrane permese PfNT1 is essential for purine salvage in the human malaria parasite Plasmodium falciparum

Kamal El Bissati, Rachel Zufferey, William H. Witola, Nicola S. Carter, Buddy Ullman, Choukri Ben Mamoun

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

The human malaria parasite Plasmodium falciparum relies on the acquisition of host purines for its survival within human erythrocytes. Purine salvage by the parasite requires specialized transporters at the parasite plasma membrane (PPM), but the exact mechanism of purine entry into the infected erythrocyte, and the primary purine source used by the parasite, remain unknown. Here, we report that transgenic parasites lacking the PPM transporter PfNT1 (P. falciparum nucleoside transporter 1) are auxotrophic for hypoxanthine, inosine, and adenosine under physiological conditions and are viable only if these normally essential nutrients are provided at excess concentrations. Transport measurements across the PPM revealed a severe reduction in hypoxanthine uptake in the knockout, whereas adenosine and inosine transport were only partially affected. These data provide compelling evidence for a sequential pathway for exogenous purine conversion into hypoxanthine using host enzymes followed by PfNT1-mediated transport into the parasite. The phenotype of the conditionally lethal mutant establishes PfNT1 as a critical component of purine salvage in P. falciparum and validates PfNT1 as a potential therapeutic target.

Original languageEnglish (US)
Pages (from-to)9286-9291
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number24
DOIs
StatePublished - Jun 13 2006

Keywords

  • Conditional knockout
  • Sequential pathway
  • Transporter

ASJC Scopus subject areas

  • General

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