NDLI: Isoprenoid Precursor Biosynthesis Is the Essential Metabolic Role of the Apicoplast during Gametocytogenesis in Plasmodium falciparum

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Isoprenoid Precursor Biosynthesis Is the Essential Metabolic Role of the Apicoplast during Gametocytogenesis in Plasmodium falciparum

Content Provider	PubMed Central
Author	Wiley, Jessica D. Merino, Emilio F. Krai, Priscilla M. Mclean, Kyle J. Tripathi, Abhai K. Joel, Vega-rodríguez Marcelo, Jacobs-lorena Michael, Klemba Cassera, Maria B.
Copyright Year	2015
Abstract	The malaria parasite harbors a relict plastid called the apicoplast and its discovery opened a new avenue for drug discovery and development due to its unusual, nonmammalian metabolism. The apicoplast is essential during the asexual intraerythrocytic and hepatic stages of the parasite, and there is strong evidence supporting its essential metabolic role during the mosquito stages of the parasite. Supply of the isoprenoid building blocks isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) is the essential metabolic function of the apicoplast during the asexual intraerythrocytic stages. However, the metabolic role of the apicoplast during gametocyte development, the malaria stages transmitted to the mosquito, remains unknown. In this study, we showed that production of IPP for isoprenoid biosynthesis is the essential metabolic function of the apicoplast during gametocytogenesis, by obtaining normal gametocytes lacking the apicoplast when supplemented with IPP. When IPP supplementation was removed early in gametocytogenesis, developmental defects were observed, supporting the essential role of isoprenoids for normal gametocytogenesis. Furthermore, mosquitoes infected with gametocytes lacking the apicoplast developed fewer and smaller oocysts that failed to produce sporozoites. This finding further supports the essential role of the apicoplast in establishing a successful infection in the mosquito vector. Our study supports isoprenoid biosynthesis as a valid drug target for development of malaria transmission-blocking inhibitors.
Related Links	http://dx.doi.org/10.1128/ec.00198-14
Ending Page	139
Page Count	12
Starting Page	128
File Format	PDF
ISSN	15359778
e-ISSN	15359786
Journal	Eukaryotic Cell
Issue Number	2
Volume Number	14
Language	English
Publisher	American Society for Microbiology
Publisher Date	2015-02-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Molecular Biology Microbiology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Microbiology

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Apicoplast and Mitochondrion in Gametocytogenesis of Plasmodium falciparum ▿ †

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