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.
Highlights
Malaria parasites are protists belonging to the genus Plasmodium
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
We show in a rodent malaria model that FAS II enzymes localize to the sporozoite and liver stage apicoplast
Summary
Malaria parasites are protists belonging to the genus Plasmodium. They are obligate intracellular parasites that have two distinct replicating life cycle forms in the mammalian host. A massive one-time replication occurs in the liver after inoculation of sporozoite stages by the bite of an infected mosquito and results in the production and release of tens of thousands infectious exo-erythrocytic merozoites (Prudencio et al, 2006). These merozoites infect red blood cells and initiate the cyclic replication that occurs within the blood stream. It is currently not well understood to what extent malaria parasites rely on parasitic scavenging of nutrients versus intrinsic synthesis for growth and replication
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