Molecular genetics of nucleoside transporters in Leishmania and African trypanosomes

Abstract

Nucleoside transporters play central roles in the biochemistry of parasitic protozoa such as Leishmania and African trypanosomes, because these parasites cannot synthesize purines de novo and are absolutely reliant upon purine salvage from their hosts. Furthermore, nucleoside transporters are important to the pharmacology of these significant human pathogens, because they mediate the uptake of purine analogs, as well as some non-purine drugs, that are selectively cytotoxic to the parasites. Recent advances in molecular biology and genomics have allowed the cloning and functional expression of several nucleoside transporter genes from Leishmania donovani and Trypanosoma brucei, providing molecular reagents for a detailed functional examination of these permeases and their role in the delivery of nutrients and drugs to the parasites. Furthermore, the molecular basis of drug-resistant mutants that are deficient in nucleoside transport functions can now be fathomed.