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

Marc Clastre1, Armelle Goubard, Anne Prel

  • 1EA2106 Biomolécules et Biotechnologies Végétales, UFR Sciences Pharmaceutiques, Université de Tours, 37200 Tours, France.

Experimental Parasitology
|April 3, 2007
PubMed

Insights

The methylerythritol phosphate (MEP) pathway for isoprenoid biosynthesis is absent in some apicomplexans but present in others. Fosmidomycin, a drug targeting this pathway, showed limited effectiveness against Eimeria tenella and Toxoplasma gondii.

Area of Science:

  • Parasitology
  • Molecular Biology
  • Biochemistry

Background:

  • The apicoplast, a unique organelle in apicomplexa, harbors essential metabolic pathways.
  • The methylerythritol phosphate (MEP) pathway for isoprenoid biosynthesis is a potential therapeutic target in apicomplexan parasites.
  • Isoprenoid metabolism and its therapeutic targeting vary significantly across apicomplexan species.

Purpose of the Study:

  • To investigate the presence of isoprenoid biosynthesis genes in coccidian parasites.
  • To evaluate the efficacy of fosmidomycin, an MEP pathway inhibitor, against Eimeria tenella and Toxoplasma gondii.

Main Methods:

  • Genome database searches for isoprenoid biosynthesis genes.
  • Gene expression analysis in Eimeria tenella and Toxoplasma gondii.
  • In vitro drug sensitivity assays using fosmidomycin.

Main Results:

  • Cryptosporidium parvum and Cryptosporidium hominis lack the MEP pathway, correlating with the absence of a plastid genome.
  • Eimeria tenella and Toxoplasma gondii possess genes for the MEP pathway, with expression detected in various life stages.
  • Fosmidomycin demonstrated poor efficacy in inhibiting the growth of Eimeria tenella and Toxoplasma gondii in vitro, even at high concentrations.

Conclusions:

  • Isoprenoid metabolism and drug sensitivity differ markedly among apicomplexan species.
  • The MEP pathway's presence and fosmidomycin's effectiveness are not conserved across all apicomplexans.
  • Further research is needed to understand the nuances of isoprenoid biosynthesis and drug targeting in diverse apicomplexan parasites.

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