Mutant/mutation
The mutant lacks expression of arginase

Protein (function)
L-arginine (Arg), a cationic amino acid, catalyzes the hydrolysis of Arg and its activity is important for maintaining ornithine levels for polyamine synthesis. Plasmodium parasites  express arginase and the dependency of blood-stage P. falciparum on polyamines for survival has been well established.
In the paper evidence is presented that L-arginine (Arg) uptake through the hepatocyte cell’s SLC7A2-encoded transporters is essential for the parasite’s development and maturation in the liver.Although the parasite may hijack the host’s biosynthesis pathway, it relies mainly upon its own arginase-AdoMetDC/ODC pathway to acquire the polyamines it needs to develop.

Phenotype
In this paper only liver stage development has been analysed. Evidence is presented that infectivity of part of the sporozoites is affected (see Additional Information).

Additional information
Evidence is presented for a bimodal pattern for the relative infectivity of both clones of the arginase-KO parasite. Of a total of 12 independent in vitro experiments performed with each of the clones, similar infection loads for WT and arginase-KO parasites were observed in approximately half of them, and a significantly lower infection by the arginase-KO parasite in the remaining half. These observations were also reproduced in an in vivo setting where the liver parasite loads were compared of mice infected with WT and arginase-KO P. berghei parasites. 8 and 5 independent rodent infection studies were carried out with arginase-KO clone #1 RMgm-228 and clone #2, respectively, and consistently a bimodal behavior was found of either arginase-KO parasite clone, similar to that observed in vitro . When employed in parallel in vitro and in vivo experiments, each independent batch of arginase-KO parasites always behaved similarly in the two experimental settings. Finally, it was investigated whether infection by the arginase-KO clone #1 parasite would be impacted by the down-modulation of the expression of the host’s enzymes involved in polyamine synthesis. When the parasite displayed impaired hepatic infectivity, the knock-down of the host’s ODC or arginase I enzymes did not further impact infection. However, when the in vitro infectivity of the arginase-KO parasite was similar to that of the WT, the knock-down of the expression of the host’s enzymes led to a decrease in infection.

It is concluded that these results suggest that the parasite relies primarily on its own polyamine synthesis pathway for hepatic development and also indicate that the parasite is able to circumvent the absence of its own polyamine biosynthesis machinery and rely on the host’s pathway to acquire the polyamines it needs to develop.

Other mutants
RMgm-228 - another mutant lacking expression of arginase (arginase-KO clone 1).