Evidence for the shikimate pathway in apicomplexan parasites

Area of Science:

• Parasitology
• Biochemistry
• Drug Discovery

Background:

• Apicomplexa parasites cause significant disease and economic losses.
• The shikimate pathway is crucial for many organisms but absent in mammals, making it an ideal drug target.
• New antiparasitic medicines are urgently needed.

Purpose of the Study:

• To investigate the presence and function of the shikimate pathway in apicomplexan parasites.
• To evaluate the potential of targeting this pathway for antiparasitic drug development.

Main Methods:

• In vitro growth inhibition assays using glyphosate.
• Reversal studies with p-aminobenzoate.
• Biochemical assays of shikimate pathway enzyme activity.
• Gene cloning of chorismate synthase.
• In vivo efficacy studies in mice.

Main Results:

• Glyphosate inhibited the in vitro growth of *Toxoplasma gondii*, *Plasmodium falciparum*, and *Cryptosporidium parvum*.
• The inhibitory effect of glyphosate was reversed by p-aminobenzoate, indicating folate precursor supply via the shikimate pathway.
• Glyphosate combined with pyrimethamine reduced *T. gondii* infection in mice.
• Four shikimate pathway enzymes were detected in *T. gondii*, and glyphosate inhibited 5-enolpyruvyl shikimate 3-phosphate synthase activity.
• Chorismate synthase genes were successfully cloned from *T. gondii* and *P. falciparum*.

Conclusions:

• Apicomplexan parasites possess a functional shikimate pathway.
• This pathway represents a viable target for novel antiparasitic drug development.
• Targeting the shikimate pathway offers a strategy for combating apicomplexan-caused diseases.