Additional remarks phenotype | Mutant/mutation
The mutant lacks expression of PANK1 and PANK2.
No information is provided on the method used to delete the two genes in the same parasite.
Protein (function)
From the paper: disruption of the two P.berghei pantothenate kinases (PANK1 and PANK2), required for phosphorylation of pantothenic acid and the synthesis of CoA, individually (pank1-, PBANKA_1022600 andpank2-, PBANKA_0611400) or together (pank1- &2-), also had little impact on asexual parasite development
Glucose consumption by Plasmodium-infected RBC increases 10-fold and these stages rely primarily on glycolysis for energy generation. Notwithstanding their dependence on glycolysis, asexual blood stages maintain a single, poorly cristate mitochondrion and are dependent on electron transport chain (ETC) activity for the re-oxidation of inner membrane dehydrogenases and pyrimidine biosynthesis. The maintenance of the mitochondrial ETC is sustained in part, by the oxidation of pyruvate (diverted from glycolysis) and the uptake and catabolism of glutamine. Pyruvate can enter the TCA cycle via two pathways; through anaplerotic reactions involving the CO2-fixing enzyme, phosphoenolpyruvate carboxylase (PEPC), or through the activity of a repurposed branched chain α-keto acid dehydrogenase (BCKDH) complex, which substitutes for the activity of the missing mitochondrial pyruvate dehydrogenase in Plasmodium and other apicomplexan parasites. Despite the essentiality of the mitochondrion, operation of the TCA cycle is not required for intra-erythrocytic growth of P.falciparum.
Plasmodium spp. lack key enzymes involved in gluconeogenesis and all developmental stages are predicted to be dependent on the uptake of sugars. However, in contrast to the asexual blood stages, there is increasing evidence that the mosquito-infective stages of Plasmodium exhibit an increased dependence on the TCA cycle and mitochondrial metabolism.
Specifically, Plasmodium gametocytes develop more complex tubular mitochondrial cristae suggestive of increased mitochondrial function. Metabolomic analyses have confirmed increased TCA metabolism in P.falciparum gametocytes and demonstrated that this is essential for gametocyte maturation. Recent genetic studies have also shown that the TCA cycle is essential for the development of P.falciparum mosquito stages, consistent with earlier work in P.berghei demonstrating that the TCA cycle and the electron transport chain are required for ookinete development and oocyst formation.
In this study a combination of metabolomic and reverse genetic approaches was used to investigate the metabolic changes that occur in key mosquito stages of P.berghei and the potential impact of these changes on parasite infection in the mosquito. We find that these stages are highly sensitive to disruptions in multiple pathways in central carbon metabolism including the TCA cycle, the utilisation of glutamine as a carbon source, intermediary carbon metabolism and coenzyme A (CoA) synthesis.
Phenotype
Normal growth of asexual blood stages. Normal gametocyte, gamete and ookinete production (ookinetes are motile). No oocyst and sporozoite production.
See also mutant RMgm-1595 for a P. yoelii mutant lacking expression of pantothenate kinase 1, putative (PANK1) that show NO ookinete formation.
See also mutant RMgm-1596 for a P. yoelii mutant lacking expression of pantothenate kinase 2, putative (PANK2) that show strongly reduced ookinete formation.
Additional information
Other mutants |