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

• DOI: 10.1073/pnas.0602590103
• Publication Date: 2006-06-03T00:47:15Z
• Authors: Kamal El Bissati; Rachel Zufferey; William H. Witola; Nicola S. Carter; Buddy Ullman; Choukri Ben Mamoun
• Keywords: Hypoxanthine; Inosine; Nucleotide salvage; Purine metabolism; Nucleoside transporter

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