Rodent and nonrodent malaria parasites differ in their phospholipid metabolic pathways.
Malaria, a disease affecting humans and other animals, is caused by a protist of the genus Plasmodium. At the intraerythrocytic stage, the parasite synthesizes a high amount of phospholipids through a bewildering number of pathways. In the human Plasmodium falciparum species, a plant-like pathway that relies on serine decarboxylase and phosphoethanolamine N-methyltransferase activities diverts host serine to provide additional phosphatidylcholine and phosphatidylethanolamine to the parasite. This feature of parasitic dependence toward its host was investigated in other Plasmodium species. In silico analyses led to the identification of phosphoethanolamine N-methyltransferase gene orthologs in primate and bird parasite genomes. However, the gene was not detected in the rodent P. berghei, P. yoelii, and P. chabaudi species. Biochemical experiments with labeled choline, ethanolamine, and serine showed marked differences in biosynthetic pathways when comparing rodent P. berghei and P. vinckei, and human P. falciparum species. Notably, in both rodent parasites, ethanolamine and serine were not significantly incorporated into phosphatidylcholine, indicating the absence of phosphoethanolamine N-methyltransferase activity. To our knowledge, this is the first study to highlight a crucial difference in phospholipid metabolism between Plasmodium species. The findings should facilitate efforts to develop more rational approaches to identify and evaluate new targets for antimalarial therapy.
Déchamps
Sandrine
S
Dynamique des Interactions Membranaires Normales et Pathologiques, UMR 5235, Centre National de la Recherche Scientifique (CNRS) - Universite Montpellier II, cc 107, Place Eugene Bataillon, 34095 Montpellier Cedex 05, France.
Maynadier
Marjorie
M
Wein
Sharon
S
Gannoun-Zaki
Laila
L
Maréchal
Eric
E
Vial
Henri J
HJ
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D008288:Malaria / Q000469:parasitology*; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000378:metabolism*; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D010802:Phylogeny; D010961:Plasmodium / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D012694:Serine; D050918:Phosphatidylethanolamine N-Methyltransferase