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The methylerythritol phosphate pathway for isoprenoid biosynthesis in coccidia: presence and sensitivity to fosmidomycin. 2007

Marc Clastre, and Armelle Goubard, and Anne Prel, and Zoia Mincheva, and Marie-Claude Viaud-Massuart, and Daniel Bout, and Marc Rideau, and Florence Velge-Roussel, and Fabrice Laurent
EA2106 Biomolécules et Biotechnologies Végétales, UFR Sciences Pharmaceutiques, Université de Tours, 37200 Tours, France.

The apicoplast is a recently discovered, plastid-like organelle present in most apicomplexa. The methylerythritol phosphate (MEP) pathway involved in isoprenoid biosynthesis is one of the metabolic pathways associated with the apicoplast, and is a new promising therapeutic target in Plasmodium falciparum. Here, we check the presence of isoprenoid genes in four coccidian parasites according to genome database searches. Cryptosporidium parvum and C. hominis, which have no plastid genome, lack the MEP pathway. In contrast, gene expression studies suggest that this metabolic pathway is present in several development stages of Eimeria tenella and in tachyzoites of Toxoplasma gondii. We studied the potential of fosmidomycin, an antimalarial drug blocking the MEP pathway, to inhibit E. tenella and T. gondii growth in vitro. The drug was poorly effective even at high concentrations. Thus, both fosmidomycin sensitivity and isoprenoid metabolism differs substantially between apicomplexan species.

UI MeSH Term Description Entries
D007555 Isoxazoles Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions. Isoxazole
D008808 Mice, Inbred CBA An inbred strain of mouse that is widely used in BIOMEDICAL RESEARCH. Mice, CBA,Mouse, CBA,Mouse, Inbred CBA,CBA Mice,CBA Mice, Inbred,CBA Mouse,CBA Mouse, Inbred,Inbred CBA Mice,Inbred CBA Mouse
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002645 Chickens Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA. Gallus gallus,Gallus domesticus,Gallus gallus domesticus,Chicken
D003044 Coccidia A subclass of protozoans commonly parasitic in the epithelial cells of the intestinal tract but also found in the liver and other organs. Its organisms are found in both vertebrates and higher invertebrates and comprise two orders: EIMERIIDA and EUCOCCIDIIDA. Coccidias
D003458 Cryptosporidium A genus of coccidian parasites of the family CRYPTOSPORIDIIDAE, found in the intestinal epithelium of many vertebrates including humans. Cryptosporidiums
D004896 Erythritol A four-carbon sugar that is found in algae, fungi, and lichens. It is twice as sweet as sucrose and can be used as a coronary vasodilator.
D005578 Fosfomycin An antibiotic produced by Streptomyces fradiae. Phosphonomycin,Fosfomycin Trometamol Salt,Fosfomycin Tromethamine,Monuril,Phosphomycin,Tromethamine, Fosfomycin
D006540 Herbicides Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE. Algaecide,Algicide,Herbicide,Algaecides,Algicides

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