López-Domínguez Jaime1,2, López-Monteon Aracely1,3, Ochoa-Martínez Paulina1,2, Eric Dumonteil4, Christian Barnabé5, Etienne Waleckx3,5,6, Rubén Gustavo Hernández-Giles1,7, Angel Ramos-Ligonio8,9. 1. LADISER de Inmunología y Biología Molecular, Facultad de Ciencias Químicas, Universidad Veracruzana, Edificio D, Prolongación de Oriente 6 #1009, Colonia Rafael Alvarado, C.P. 94340, 86039, Orizaba, Veracruz, Mexico. 2. Doctorado en Ciencias Biomédicas, Universidad Veracruzana, Xalapa, Veracruz, Mexico. 3. Asociacion Chagas con Ciencia y Conocimiento A.C., Orizaba, Veracruz, Mexico. 4. Department of Tropical Medicine, Tulane University, School of Public Health and Tropical Medicine, New Orleans, LA, USA. 5. Institut de Recherche pour le Développement, UMR INTERTRYP IRD, CIRAD, Université de Montpellier, Montpellier, France. 6. Laboratorio de Parasitología, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi", Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico. 7. Maestría en Ciencias en Procesos Biológicos, Facultad de Ciencias Químicas, Universidad Veracruzana, Orizaba, Veracruz, Mexico. 8. LADISER de Inmunología y Biología Molecular, Facultad de Ciencias Químicas, Universidad Veracruzana, Edificio D, Prolongación de Oriente 6 #1009, Colonia Rafael Alvarado, C.P. 94340, 86039, Orizaba, Veracruz, Mexico. angramos@uv.mx. 9. Asociacion Chagas con Ciencia y Conocimiento A.C., Orizaba, Veracruz, Mexico. angramos@uv.mx.
Abstract
PURPOSE: 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). METHODS: 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. RESULTS: 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, 6.8 μM), isolates SRB1 and Zn3 were partially resistant (IC50, 12.8 μM and 12.7 μM) and isolate Sum3 showed a high degree of resistance to NFX (IC50, 21.4 µM). We also found an association between decreased NTR1 or OYE gene expression with NFX resistance. CONCLUSION: 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.
PURPOSE: 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). METHODS: 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. RESULTS: 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, 6.8 μM), isolates SRB1 and Zn3 were partially resistant (IC50, 12.8 μM and 12.7 μM) and isolate Sum3 showed a high degree of resistance to NFX (IC50, 21.4 µM). We also found an association between decreased NTR1 or OYE gene expression with NFX resistance. CONCLUSION: 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.
Authors: Margoth Moreno; Daniella A D'ávila; Marcelo N Silva; Lúcia Mc Galvão; Andrea M Macedo; Egler Chiari; Eliane D Gontijo; Bianca Zingales Journal: Mem Inst Oswaldo Cruz Date: 2010-11 Impact factor: 2.743
Authors: B Zingales; S G Andrade; M R S Briones; D A Campbell; E Chiari; O Fernandes; F Guhl; E Lages-Silva; A M Macedo; C R Machado; M A Miles; A J Romanha; N R Sturm; M Tibayrenc; A G Schijman Journal: Mem Inst Oswaldo Cruz Date: 2009-11 Impact factor: 2.743
Authors: Luciana Lima; Oneida Espinosa-Álvarez; Paola A Ortiz; Javier A Trejo-Varón; Julio C Carranza; C Miguel Pinto; Myrna G Serrano; Gregory A Buck; Erney P Camargo; Marta M G Teixeira Journal: Acta Trop Date: 2015-07-19 Impact factor: 3.112
Authors: Carolina Aquilino; Maria Luisa Gonzalez Rubio; Elena Maria Seco; Leticia Escudero; Laura Corvo; Manuel Soto; Manuel Fresno; Francisco Malpartida; Pedro Bonay Journal: PLoS One Date: 2012-07-31 Impact factor: 3.240