Type II Fatty Acid Biosynthesis Is Essential for Plasmodium falciparum Sporozoite Development in the Midgut of Anopheles Mosquitoes

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 acidsde novo via the type two fatty acid biosynthesis pathway (FAS-II). Here, we study the FAS-II pathway inPlasmodium 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 inPlasmodium falciparum by assessing the functional consequences of deletingfabI andfabB/F . Targeted deletion or disruption of these genes inP. falciparum did not affect asexual blood-stage replication or the generation of midgut oocysts; however, subsequent sporozoite development was abolished. We conclude that theP. falciparum FAS-II pathway is essential for sporozoite development within the midgut oocyst. These findings reveal an important distinction from the rodentPlasmodium parasitesP. berghei andP. 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 theAnopheles mosquito midgut.