Molecular Characterization of Four Mexican Isolates of Trypanosoma cruzi and Their Profile Susceptibility to Nifurtimox

Abstract

The objective of this study was to molecularly characterize Mexican isolates of T. cruzi obtained from infected triatomine bugs (the vectors of T. cruzi) and to evaluate their susceptibility to Nifurtimox (NFX). Three isolates obtained from Triatoma dimidiata (collected in the State of Veracruz) and one isolate obtained from Triatoma bassolsae (collected in the State of Puebla) were molecularly characterized and the expression of genes associated with natural resistance to NFX was analyzed by qPCR. Molecular characterization by PCR showed that isolates Zn3, Zn5, and SRB1 belong to the DTU TcI, while isolate Sum3 belongs to TcIV. The latter was also confirmed by sequencing of mitochondrial genes. Isolate Zn5 was the most sensitive to treatment with NFX (IC50, 6.8μM), isolates SRB1 and Zn3 were partially resistant (IC50, 12.8μM and 12.7μM) and isolate Sum3 showed a high degree of resistance to NFX (IC50, 21.4µM). We also found an association between decreased NTR1 or OYE gene expression with NFX resistance. Our results also evidenced a high variability in the susceptibility to NFX of these T. cruzi isolates Central and Southeastern Mexico, suggesting the presence of naturally resistant isolates circulating in the country. These results have important implications for defining treatment policies for patients with Chagas disease.