Growth of Toxoplasma gondii is inhibited by aryloxyphenoxypropionate herbicides targeting acetyl-CoA carboxylase

Aryloxyphenoxypropionates, inhibitors of the plastid acetyl-CoA carboxylase (ACC) of grasses, also inhibit Toxoplasma gondii ACC. Clodinafop, the most effective of the herbicides tested, inhibits growth of T. gondii in human fibroblasts by 70% at 10 mu M in 2 days and effectively eliminates the para site in 2-4 days at 10-100 mu M Clodinafop is not toxic to the host cell ev en at much higher concentrations. Parasite growth inhibition by different h erbicides is correlated with their ability to inhibit ACC enzyme activity, suggesting that ACC is a target for these agents. Fragments of genes encodi ng the biotin carboxylase domain of multidomain ACCs of T, gondii, Plasmodi um falciparum. Plasmodiom knowlesi, and Cryptosporidium parvum were sequenc ed. One T. gondii ACC (ACC1) amino acid sequence clusters with P. falciparu m ACC, P. knowlesi ACC, and the putative Cyclotella cryptica chloroplast AC C. Another sequence (ACC2) clusters with that of C. parvum ACC, probably th e cytosolic form.