title: Disruption of the Plasmodium falciparum PfPMT gene results in a complete loss of phosphatidylcholine biosynthesis via the serine-decarboxylase-phosphoethanolamine-methyltransferase pathway and severe growth and survival defects.
abstract: Biochemical studies in the human malaria parasite, Plasmodium falciparum, indicated that in addition to the pathway for synthesis of phosphatidylcholine from choline (CDP-choline pathway), the parasite synthesizes this major membrane phospholipid via an alternative pathway named the serine-decarboxylase-phosphoethanolamine-methyltransferase (SDPM) pathway using host serine and ethanolamine as precursors. However, the role the transmethylation of phosphatidylethanolamine plays in the biosynthesis of phosphatidylcholine and the importance of the SDPM pathway in the parasite's growth and survival remain unknown. Here, we provide genetic evidence that knock-out of the PfPMT gene encoding the phosphoethanolamine methyltransferase enzyme completely abrogates the biosynthesis of phosphatidylcholine via the SDPM pathway. Lipid analysis in knock-out parasites revealed that unlike in mammalian and yeast cells, methylation of phosphatidylethanolamine to phosphatidylcholine does not occur in P. falciparum, thus making the SDPM and CDP-choline pathways the only routes for phosphatidylcholine biosynthesis in this organism. Interestingly, loss of PfPMT resulted in significant defects in parasite growth, multiplication, and viability, suggesting that this gene plays an important role in the pathogenesis of intraerythrocytic Plasmodium parasites.
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030.
authors.forename: William Harold
authors.initials: WH
authors.lastname: Witola
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030.
authors.forename: Kamal
authors.initials: K
authors.lastname: El Bissati
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pessi
authors.affiliation: Department of Chemistry and Department of Biochemistry, Cellular and Molecular Biology, Georgetown University, Washington, D. C. 20057.
authors.forename: Changan
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Chemistry and Department of Biochemistry, Cellular and Molecular Biology, Georgetown University, Washington, D. C. 20057.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Roepe
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030. Electronic address: choukri@up.uchc.edu.
authors.forename: Choukri Ben
authors.initials: CB
authors.lastname: Mamoun
mesh_terms: D000818:Animals; D019856:Ethanolamine / Q000378:metabolism; D017353:Gene Deletion; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000096:biosynthesis* / Q000235:genetics; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism
chemical_list: D010713:Phosphatidylcholines; D015800:Protozoan Proteins; D012694:Serine; D019856:Ethanolamine; D008780:Methyltransferases; C102844:phosphoethanolamine methyltransferase