title: Type II fatty acid synthesis is essential only for malaria parasite late liver stage development.
abstract: Intracellular malaria parasites require lipids for growth and replication. They possess a prokaryotic type II fatty acid synthesis (FAS II) pathway that localizes to the apicoplast plastid organelle and is assumed to be necessary for pathogenic blood stage replication. However, the importance of FAS II throughout the complex parasite life cycle remains unknown. We show in a rodent malaria model that FAS II enzymes localize to the sporozoite and liver stage apicoplast. Targeted deletion of FabB/F, a critical enzyme in fatty acid synthesis, did not affect parasite blood stage replication, mosquito stage development and initial infection in the liver. This was confirmed by knockout of FabZ, another critical FAS II enzyme. However, FAS II-deficient Plasmodium yoelii liver stages failed to form exo-erythrocytic merozoites, the invasive stage that first initiates blood stage infection. Furthermore, deletion of FabI in the human malaria parasite Plasmodium falciparum did not show a reduction in asexual blood stage replication in vitro. Malaria parasites therefore depend on the intrinsic FAS II pathway only at one specific life cycle transition point, from liver to blood.
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Vaughan
authors.forename: Matthew T
authors.initials: MT
authors.lastname: O'Neill
authors.forename: Alice S
authors.initials: AS
authors.lastname: Tarun
authors.forename: Nelly
authors.initials: N
authors.lastname: Camargo
authors.forename: Thuan M
authors.initials: TM
authors.lastname: Phuong
authors.forename: Ahmed S I
authors.initials: AS
authors.lastname: Aly
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
authors.forename: Stefan H I
authors.initials: SH
authors.lastname: Kappe
mesh_terms: D000818:Animals; D001769:Blood / Q000469:parasitology*; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D005260:Female; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D006801:Humans; D008099:Liver / Q000469:parasitology*; D008288:Malaria / Q000469:parasitology; D053858:Metabolic Networks and Pathways; D051379:Mice; D008807:Mice, Inbred BALB C; D015388:Organelles / Q000737:chemistry; D010963:Plasmodium falciparum / Q000737:chemistry / Q000254:growth & development* / Q000378:metabolism*; D010967:Plasmodium yoelii / Q000737:chemistry / Q000254:growth & development* / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004798:Enzymes; D005227:Fatty Acids; D015800:Protozoan Proteins