Sulfadiazine resistance in Toxoplasma gondii: no involvement of overexpression or polymorphisms in genes of therapeutic targets and ABC transporters.
Fiche publication
Date publication
janvier 2013
Journal
Parasite (Paris, France)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr VELARD Frédéric, Pr VILLENA Isabelle
Tous les auteurs :
Doliwa C, Escotte-Binet S, Aubert D, Sauvage V, Velard F, Schmid A, Villena I
Lien Pubmed
Résumé
Several treatment failures have been reported for the treatment of toxoplasmic encephalitis, chorioretinitis, and congenital toxoplasmosis. Recently we found three Toxoplasma gondii strains naturally resistant to sulfadiazine and we developed in vitro two sulfadiazine resistant strains, RH-R(SDZ) and ME-49-R(SDZ), by gradual pressure. In Plasmodium, common mechanisms of drug resistance involve, among others, mutations and/or amplification within genes encoding the therapeutic targets dhps and dhfr and/or the ABC transporter genes family. To identify genotypic and/or phenotypic markers of resistance in T. gondii, we sequenced and analyzed the expression levels of therapeutic targets dhps and dhfr, three ABC genes, two Pgp, TgABC.B1 and TgABC.B2, and one MRP, TgABC.C1, on sensitive strains compared to sulfadiazine resistant strains. Neither polymorphism nor overexpression was identified. Contrary to Plasmodium, in which mutations and/or overexpression within gene targets and ABC transporters are involved in antimalarial resistance, T. gondii sulfadiazine resistance is not related to these toxoplasmic genes studied.
Mots clés
ATP-Binding Cassette Transporters, genetics, Animals, Antiprotozoal Agents, pharmacology, Base Sequence, Cercopithecus aethiops, Dihydropteroate Synthase, antagonists & inhibitors, Drug Resistance, genetics, Gene Expression Regulation, Genotype, Molecular Sequence Data, Phenotype, Polymorphism, Genetic, Sulfadiazine, pharmacology, Tetrahydrofolate Dehydrogenase, drug effects, Toxoplasma, classification, Vero Cells
Référence
Parasite. 2013 ;20:19