Mutant/mutation

Protein (function)
Plasmodium lacks the enzymatic machinery necessary for the synthesis of the purine ring de novo and rely solely on the uptake of host purines for DNA synthesis. For P. falciparum it has been demonstrated that the translocation of host purines into the parasite is mainly mediated by the plasma membrane permease PfNT1 (nucleotide transporter 1). Genetic studies demonstrated that PfNT1 plays an essential role in parasite development and replication within human erythrocytes and parasites lacking PfNT1 are conditionally lethal, growing only when purines are provided at supra-physiological concentrations (El Bissati et al., 2006, PNAS 103, 9286-91; El Bissati, 2008, Mol. Biochem. Parasitol. 161, 130-9).

Phenotype
Asexual blood stages show a strongly reduced growth and multiplication. Cloning of the mutant by limiting dilution was not possible (see 'Additional information').

Additional information
Currently, no P. yoelii gene model/systematic id is available from both PlasmoDB and GeneDB.
Transcriptional profiling of PyNT1 revealed a constitutive expression pattern in multiple life cycle stages of P. yoelii.

It was not possible to clone Pynt1- parasites by limited dilution using 1, 5, 10 and 50 parasites per mouse. Only after starting with 100 Pynt1- parasites as the intravenous inoculum, 15–20% of the recipient mice became patent 11–14 days post inoculation (p.i.).

Immunization of inbred and outbred mouse strains with a single low dose of Pynt1- blood stages (50-100 parasites) did not induce any patent infections and conferred complete sterile protection against lethal blood stage and sporozoite challenges. In order to investigate which type of immune responses are mediating sterile protective immunity the following mice strains were infected:  alpha–beta T cell-deficient mice (Tcra(tm1Mom)/J), which lack the alpha–beta T-cell receptor, and mature B cell-deficient mice [Igh-6(tm1Cgn)/J]. Both transgenic mouse strains are in the C57BL/6 genetic background. Both transgenic mouse strains were not protected and developed lethal parasitemias, which were first detected in blood smears at day 4 after challenge. WT C57BL/6 control mice showed complete protection. These analyses indicate that both cellular and humoral immune responses are essential for sterile protection.

Other mutants