PMID- 19068099 OWN - NLM STAT- MEDLINE DCOM- 20090515 LR - 20240109 IS - 1462-5822 (Electronic) IS - 1462-5814 (Print) IS - 1462-5814 (Linking) VI - 11 IP - 3 DP - 2009 Mar TI - Type II fatty acid synthesis is essential only for malaria parasite late liver stage development. PG - 506-20 LID - 10.1111/j.1462-5822.2008.01270.x [doi] AB - 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. FAU - Vaughan, Ashley M AU - Vaughan AM AD - Seattle Biomedical Research Institute, Seattle, WA 98109, USA. FAU - O'Neill, Matthew T AU - O'Neill MT FAU - Tarun, Alice S AU - Tarun AS FAU - Camargo, Nelly AU - Camargo N FAU - Phuong, Thuan M AU - Phuong TM FAU - Aly, Ahmed S I AU - Aly AS FAU - Cowman, Alan F AU - Cowman AF FAU - Kappe, Stefan H I AU - Kappe SH LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20081203 PL - India TA - Cell Microbiol JT - Cellular microbiology JID - 100883691 RN - 0 (Enzymes) RN - 0 (Fatty Acids) RN - 0 (Protozoan Proteins) SB - IM MH - Animals MH - Blood/*parasitology MH - Enzymes/genetics/metabolism MH - Fatty Acids/*biosynthesis MH - Female MH - Gene Deletion MH - Gene Knockout Techniques MH - Humans MH - Liver/*parasitology MH - Malaria/parasitology MH - Metabolic Networks and Pathways MH - Mice MH - Mice, Inbred BALB C MH - Organelles/chemistry MH - Plasmodium falciparum/chemistry/*growth & development/*metabolism MH - Plasmodium yoelii/chemistry/*growth & development/*metabolism MH - Protozoan Proteins/genetics/metabolism PMC - PMC2688669 EDAT- 2008/12/11 09:00 MHDA- 2009/05/16 09:00 PMCR- 2009/06/01 CRDT- 2008/12/11 09:00 PHST- 2008/12/11 09:00 [pubmed] PHST- 2009/05/16 09:00 [medline] PHST- 2008/12/11 09:00 [entrez] PHST- 2009/06/01 00:00 [pmc-release] AID - CMI1270 [pii] AID - 10.1111/j.1462-5822.2008.01270.x [doi] PST - ppublish SO - Cell Microbiol. 2009 Mar;11(3):506-20. doi: 10.1111/j.1462-5822.2008.01270.x. Epub 2008 Dec 3.