Article

Projet
Conception, synthèse et étude de nouveaux hétérocycles azotés d'intérêts biologiques  
Ahcène BOUMENDJEL,   
Titre
High-content imaging assay to evaluate toxoplasma gondii invasion and proliferation: a multiparametric assay to screen new compounds  
Auteurs
B. Touquet, L. Pellissier, P. Cavailles, W. Yi, V. Bellini, C. Mercier, M.-F. Delauw, A. Boumendjel, D. Aldebert.
Edition
PlosOne, 2018, accepté
Année
2018
Résumé
Toxoplasma gondii is an intracellular protozoan parasite widely distributed in animals and humans. Invasion of host cells and parasite proliferation are essential steps in Toxoplasma pathology. The objective of this study was to develop and validate a novel automatic High Content Imaging (HCI) assay to study T. gondii invasion and proliferation. We tested various fluorescent markers and strategies of image analysis to obtain an automated method providing results comparable to those from gold standard invasion and proliferation assays. No significant difference was observed between the results obtained from the HCI assay and the standard assays (manual fluorescence microscopy and incorporation of 3H-uracil). We demonstrated that the assay developed here is a robust and time-saving assay. This automated technology was used to screen a library of compounds belonging to four classes of either natural compounds or synthetic derivatives. The inhibition of the parasite proliferation and the host cell toxicity were measured in the same assay and led to the identification of one hit, a thiosemicarbazone, that allows important inhibition of Toxoplasma proliferation while being relatively safe for the host cells.