Differential gene expression in benznidazole-resistant Trypanosoma cruzi parasites.
We analyzed the differential gene expression among representative Trypanosoma cruzi stocks in relation to benznidazole exposures using a random differentially expressed sequences (RADES) technique. Studies were carried out with drug pressure both at the natural susceptibility level of the wild-type parasite (50% inhibitory concentration for the wild type) and at different resistance levels. The pattern of differential gene expression performed with resistant stocks was compared to the population structure of this parasite, established by random amplified polymorphic DNA analysis and multilocus enzyme electrophoresis. A RADES band polymorphism was observed, and over- or underexpression was linked to the resistance level of the stock. The analysis of RADES bands suggested that different products may be involved in benznidazole resistance mechanisms. No significant association was found between phylogenetic clustering and benznidazole susceptibility. Benznidazole resistance may involve several mechanisms, depending on the level of drug exposure.
Villarreal
Diana
D
Génétique et Evolution des Maladies Infectieuses G.E.M.I., UMR 2724 CNRS/IRD, UR 165 IRD, Centre de Recherche IRD, 911 avenue Agropolis, BP 64501, 34394 Montpellier Cedex 5, France.
Nirdé
Philippe
P
Hide
Mallorie
M
Barnabé
Christian
C
Tibayrenc
Michel
M
D000818:Animals; D004351:Drug Resistance; D004586:Electrophoresis / Q000379:methods; D004798:Enzymes / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009593:Nitroimidazoles / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D016133:Polymerase Chain Reaction / Q000379:methods; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D019105:Random Amplified Polymorphic DNA Technique; D017422:Sequence Analysis, DNA; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development
D004798:Enzymes; D009593:Nitroimidazoles; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; C009999:benzonidazole