Rodent and nonrodent malaria parasites differ in their phospholipid metabolic pathways |
| |
Authors: | Sandrine D??champs Marjorie Maynadier Sharon Wein Laila Gannoun-Zaki Eric Mar??chal and Henri J Vial |
| |
Institution: | *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;†UMR 5168 CNRS-CEA-INRA-Universite Joseph Fourier, Institut de Recherches en Technologies et Sciences pour le Vivant, 17 avenue des Martyrs, 38058 Grenoble, France |
| |
Abstract: | 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. |
| |
Keywords: | Plasmodium falciparum Plasmodium berghei Plasmodium vinckei lipid phospholipid biosynthesis phosphatidylcholine phosphatidylethanolamine phosphatidylserine phosphoethanolamine N-methyltransferase serine decarboxylase |
本文献已被 ScienceDirect 等数据库收录! |
|