title: Type II fatty acid biosynthesis is essential for Plasmodium falciparum sporozoite development in the midgut of Anopheles mosquitoes.
abstract: The prodigious rate at which malaria parasites proliferate during asexual blood-stage replication, midgut sporozoite production, and intrahepatic development creates a substantial requirement for essential nutrients, including fatty acids that likely are necessary for parasite membrane formation. Plasmodium parasites obtain fatty acids either by scavenging from the vertebrate host and mosquito vector or by producing fatty acids de novo via the type two fatty acid biosynthesis pathway (FAS-II). Here, we study the FAS-II pathway in Plasmodium falciparum, the species responsible for the most lethal form of human malaria. Using antibodies, we find that the FAS-II enzyme FabI is expressed in mosquito midgut oocysts and sporozoites as well as liver-stage parasites but not during the blood stages. As expected, FabI colocalizes with the apicoplast-targeted acyl carrier protein, indicating that FabI functions in the apicoplast. We further analyze the FAS-II pathway in Plasmodium falciparum by assessing the functional consequences of deleting fabI and fabB/F. Targeted deletion or disruption of these genes in P. falciparum did not affect asexual blood-stage replication or the generation of midgut oocysts; however, subsequent sporozoite development was abolished. We conclude that the P. falciparum FAS-II pathway is essential for sporozoite development within the midgut oocyst. These findings reveal an important distinction from the rodent Plasmodium parasites P. berghei and P. yoelii, where the FAS-II pathway is known to be required for normal parasite progression through the liver stage but is not required for oocyst development in the Anopheles mosquito midgut.
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Ben C L
authors.initials: BC
authors.lastname: van Schaijk
authors.forename: T R Santha
authors.initials: TR
authors.lastname: Kumar
authors.forename: Martijn W
authors.initials: MW
authors.lastname: Vos
authors.forename: Adam
authors.initials: A
authors.lastname: Richman
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: van Gemert
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Abraham G
authors.initials: AG
authors.lastname: Eappen
authors.forename: Kim C
authors.initials: KC
authors.lastname: Williamson
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Morahan
authors.forename: Matt
authors.initials: M
authors.lastname: Fishbaugher
authors.forename: Mark
authors.initials: M
authors.lastname: Kennedy
authors.forename: Nelly
authors.initials: N
authors.lastname: Camargo
authors.forename: Shahid M
authors.initials: SM
authors.lastname: Khan
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Janse
authors.forename: Kim Lee
authors.initials: KL
authors.lastname: Sim
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
authors.forename: Stefan H I
authors.initials: SH
authors.lastname: Kappe
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.forename: David A
authors.initials: DA
authors.lastname: Fidock
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Vaughan
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D005227:Fatty Acids / Q000096:biosynthesis*; D041981:Gastrointestinal Tract / Q000469:parasitology; D006801:Humans; D007303:Insect Vectors / Q000469:parasitology*; D016778:Malaria, Falciparum / Q000469:parasitology; D033661:Oocysts / Q000254:growth & development / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D034101:Sporozoites / Q000254:growth & development / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D015800:Protozoan Proteins