FEMS Microbiol Lett. 2008 Mar 26 [Epub ahead of print]
Itraconazole affects Toxoplasma gondii endodyogeny
Martins-Duarte ED, de Souza W, Vommaro RC.
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, CCS Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
The antifungal agent itraconazole is an effective drug against systemic mycoses inhibiting cytochrome P-450-mediated ergosterol synthesis, essential for fungal survival. In this work, we show the activity of this azole as a potential agent against Toxoplasma gondii, the causative agent of toxoplasmosis. Monolayers of LLC-MK2 epithelial cells infected with tachyzoites of RH strain were incubated with different concentrations of itraconazole for 24 and 48 h. The IC(50) values obtained were 114.0 and 53.6 nM for 24 and 48 h, respectively. Transmission electron microscopy (TEM) analysis of itraconazole-treated intracellular tachyzoites showed endoplasmic reticulum and nuclear envelope swelling. The drug also caused rupture of the parasite's surface membrane and affected the parasite's division by endodyogeny. This observation was confirmed both by fluorescence microscopy of cells labeled with diamidino-2-phenylindole and by three-dimensional reconstruction of serial thin sections analyzed by TEM. The treatment with itraconazole led to the formation of a mass of daughter cells, suggesting the interruption of the scission process during the parasite's cell division.
PMID: 18371067 [PubMed - as supplied by publisher]