All protozoan parasites are lacking the pathway to synthesize
purines de novo and therefore they depend on their host cells to provide
purines. A number of highly conserved
nucleoside transporter (NT)
proteins are encoded in
malaria parasite genomes, of which NT1 is characterized in Plasmodium falciparum and P. yoelii as a plasma membrane
protein that is responsible for salvage of
purines from the host, and NT2 is an endoplasmic membrane NT
protein. Whereas NT3 is only present in primate
malaria parasites, little is known about NT4, which is conserved in all
malaria parasite species. Herein, we targeted NT4 gene for deletion in P. berghei. NT4 knockout parasites developed normally as blood stages, ookinetes and formed oocysts with sporozoites compared with wild-type (WT) P. berghei ANKA parasites. However, nt4(-) sporozoites showed significantly decreased egress from oocysts to hemolymph, significant reduction of colonization of the salivary glands, and complete abolishment of
infection of the mammalian host by salivary gland and hemolymph sporozoites. Therefore, we identify NT4 as a NT that is important, not for replication and growth, but for sporozoite infectivity functions.