SELECTION AND CHARACTERIZATION OF TOXOPLASMA-GONDII MUTANTS RESISTANTTO ARTEMISININ

Toxoplasma gondii infection, like malaria, is sensitive to inhibition by artemisinin (ART). Mechanisms of action for ART in malaria treatmen t have been proposed, but little is known about its effects in T. gond ii infection. To better understand its inhibitory effects on T. gondii , mutants resistant to ART were selected by progressive culture in per missive levels of the drug. Five clonal isolates were established and characterized. The isolates were similar to 65-fold less sensitive to ART than is the parental RH and showed cross-resistance to the ART der ivatives dihydroartemisinin and artemether. In addition to ART resista nce, 1 clone (C9) formed morphologically unusual parasitophorous vacuo les and another (A2) was avirulent for mice and protected mice from ch allenge with the wild type. These clonal T. gondii mutant isolates wil l be useful for the study of not only the mechanism of action of ART b ut also parasite vacuole biology and virulence factors.