Benznidazole-resistance in Trypanosoma cruzi: Evidence that distinct mechanisms can act in concert☆

“Benznidazole-resistance in Trypanosoma cruzi: Evidence that distinct mechanisms can act in concert’’ [Mol. Biochem. Parasit. (2014) 193, 17–19]

Benznidazole-Resistance in Trypanosoma cruzi Is a Readily Acquired Trait That Can Arise Independently in a Single Population

Benznidazole is the frontline drug used against Trypanosoma cruzi, the causative agent of Chagas disease. However, treatment failures are often reported. Here, we demonstrate that independently acquired mutations in the gene encoding a mitochondrial nitroreductase (TcNTR) can give rise to distinct drug-resistant clones within a single population. Following selection of benznidazole-resistant pa...

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...

Effects of some fractions from Achillea biebersteinii and A.millefolium on the epimastigotes of Trypanosoma cruzi

Higher plants are a potential source of new drugs to improve the treatment of Chagase disease, which is affecting 16-18 million people, with more than 100 million exposed to the risk of infection (Ambrozin et al., 2004; Coura & Castro, 2002). Current therapy is unsatisfactory, because the only two drugs available, benznidazole and nifortimox possess severe side effects and their activity is lim...

Trypanosoma cruzi: acute and long-term infection in the vertebrate host can modify the response to benznidazole.

We analyzed the influence of Trypanosoma cruzi maintenance in different hosts (dog and mouse) on its susceptibility to benznidazole treatment. Five T. cruzi stocks were isolated from dogs inoculated with Be-62 or Be-78 strain (both sensitive to benznidazole) 2-10 years ago, and the benznidazole sensitivity was then determined using the mouse as experimental model. The different T. cruzi stocks ...