Intracellular Toxoplasma gondii grown in human foreskin fibroblast cells transported nitrobenzylthioinosine [
NBMPR; 6-[(4-nitrobenzyl)mercapto]-9-beta-D-ribofuranosylpurine], an inhibitor of
nucleoside transport in mammalian cells, as well as the nonphysiological beta-L-enantiomers of
purine nucleosides, beta-L-
adenosine, beta-L-
deoxyadenosine, and beta-L-
guanosine. The beta-L-
pyrimidine nucleosides, beta-L-
uridine, beta-L-
cytidine, and beta-L-
thymidine, were not transported. The uptake of
NBMPR and the nonphysiological
purine nucleoside beta-L-enantiomers by the intracellular parasites also implies that Toxoplasma-infected cells can transport these
nucleosides. In sharp contrast, under the same conditions, uninfected fibroblast cells did not transport
NBMPR or any of the unnatural beta-L-
nucleosides. beta-D-
Adenosine and
dipyridamole, another inhibitor of
nucleoside transport, inhibited the uptake of
NBMPR and beta-L-stereoisomers of the
purine nucleosides by intracellular Toxoplasma and Toxoplasma-infected cells. Furthermore,
infection with a Toxoplasma mutant deficient in parasite
adenosine/
purine nucleoside transport reduced or abolished the uptake of beta-D-
adenosine,
NBMPR, and
purine beta-L-
nucleosides. Hence, the presence of the Toxoplasma
adenosine/
purine nucleoside transporters is apparently essential for the uptake of
NBMPR and
purine beta-L-
nucleosides by intracellular Toxoplasma and Toxoplasma-infected cells. These results also demonstrate that, in contrast to the mammalian
nucleoside transporters, the Toxoplasma
adenosine/
purine nucleoside transporter(s) lacks stereospecificity and substrate specificity in the transport of
purine nucleosides. In addition,
infection with T. gondii confers the properties of the parasite's
purine nucleoside transport on the parasitized host cells and enables the infected cells to transport
purine nucleosides that were not transported by uninfected cells. These unique characteristics of
purine nucleoside transport in T. gondii may aid in the identification of new promising antitoxoplasmic drugs.