In vitro activities of two antimitotic compounds, pancratistatin and 7-deoxynarciclasine, against Encephalitozoon intestinalis, a microsporidium causing infections in humans

The antiparasitic effect of a collection of compounds with antimitotic acti vity has been tested on a mammalian cell line infected with Encephalitozoon intestinalis, a microsporidian causing intestinal and systemic infection i n immunocompromised patients. The antiparasitic effect was evaluated by cou nting the number of parasitophorous vacuoles detected by immunofluorescence . Out of 526 compounds tested, 2 (pancratistatin and 7-deoxynarciclasine) i nhibited the infection without affecting the host cell. The 50% inhibitory concentrations (IC(50)s) of pancratistatin and 7-deoxynarciclasine for E. i ntestinalis were 0.18 muM and 0.2 muM, respectively, approximately eightfol d lower than the IC(50)s of these same compounds against the host cells. El ectron microscopy confirmed the gradual decrease in the number of parasitop horous vacuoles and showed that of the two life cycle phases, sporogony was more sensitive to the inhibitors than merogony. Furthermore, the persisten ce of meronts in some cells apparently devoid of sporonts and spores indica ted that the inhibitors block development rather than entry of the parasite into the host cell. The occurrence of binucleate sporoblasts and spores su ggests that these inhibitors blocked a specific phase of cell division.