Inhibition of Toxoplasma gondii replication by dinitroaniline herbicides

Experimental Parasitology
T J StokkermansD S Roos

Abstract

Submicromolar concentrations of several dinitroaniline herbicides have been found to specifically inhibit intracellular replication of the protozoan parasite Toxoplasma gondii. IC50 concentrations for T. gondii survival were approximately 100 nM for ethalfluralin and oryzalin and approximately 300 nM for trifluralin. Primary human fibroblasts employed as host cells for parasite culture were unaffected at > 100-fold higher concentrations. Extracellular parasites were unaffected by these drugs, but within 8 hr after treatment of infected cell cultures, intracellular tachyzoites formed large amorphous bodies containing distorted nuclei. Parasite cytokinesis was completely blocked by drug treatment; nucleic acid synthesis, however, continued at near-normal levels for several days in the continuous presence of drug. All dinitroanilines appear to block nuclear division by inhibition of intranuclear spindle formation, but other cytoskeletal components were differentially affected by the various drugs tested. Subpellicular microtubules were absent in oryzalin-treated parasites, and large fragments of the inner membrane complex were observed throughout the parasite cytoplasm. In contrast, subpellicular microtubules and the inner membran...Continue Reading

Citations

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