Phenotypic diversity and drug susceptibility of Trypanosoma cruzi TcV clinical isolates
| Autor: | Adriana Parodi-Talice, Jacqueline Búa, Alina Elizabeth Perrone, Luz P. Quebrada Palacio, Miriam Postan, Yolanda Hernandez-Vasquez, Mariela N. González |
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| Přispěvatelé: | Quebrada Palacio L.P., González M.N., Hernandez-Vasquez Y., Perrone A.E., Parodi Tálice Adriana Magdalena, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología, Bua J., Postan M. |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Chagas disease Adult Male Genotype Trypanosoma cruzi 030231 tropical medicine Argentina Drug Resistance Protozoan Proteins lcsh:Medicine Parasitemia Biology Microbiology Ciencias Biológicas purl.org/becyt/ford/1 [https] 03 medical and health sciences Mice 0302 clinical medicine Biología Celular Microbiología Phenotypic diversity Chlorocebus aethiops medicine Animals Humans Chagas Disease Nifurtimox Amastigote lcsh:Science purl.org/becyt/ford/1.6 [https] Vero Cells Multidisciplinary lcsh:R Middle Aged medicine.disease biology.organism_classification Trypanocidal Agents 030104 developmental biology Phenotype Benznidazole Female lcsh:Q Congenital transmission Trypanosomiasis CIENCIAS NATURALES Y EXACTAS medicine.drug Pentamidine |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET PLoS ONE, Vol 13, Iss 9, p e0203462 (2018) COLIBRI Universidad de la República instacron:Universidad de la República |
| DOI: | 10.1371/journal.pone.0203462 |
| Popis: | Trypanosoma cruzi is a genetically heterogeneous group of organisms that cause Chagas disease. It has been long suspected that the clinical outcome of the disease and response to therapeutic agents are, at least in part, related to the genetic characteristics of the parasite. Herein, we sought to validate the significance of the genotype of T. cruzi isolates recovered from patients with different clinical forms of Chagas disease living in Argentina on their biological behaviour and susceptibility to drugs. Genotype identification of the newly established isolates confirmed the reported predominance of TcV, with a minor frequency of TcI. Epimastigote sensitivity assays demonstrated marked dissimilar responses to benznidazole, nifurtimox, pentamidine and dihydroartemisinin in vitro. Two TcV isolates exhibiting divergent response to benznidazole in epimastigote assays were further tested for the expression of anti-oxidant proteins. Benznidazole-resistant BOL-FC10A epimastigotes had decreased expression of Old Yellow Enzyme and cytosolic superoxide dismutase, and over-expression of mitochondrial superoxide dismutase and tryparedoxin- 1, compared to benznidazole-susceptible AR-SE23C parasites. Drug sensitivity assays on intracellular amastigotes and trypomastigotes reproduced the higher susceptibility of AR-SE23C over BOL-FC10A parasites to benznidazole observed in epimastigotes assays. However, the susceptibility/resistance profile of amastigotes and trypomastigotes to nifurtimox, pentamidine and dihydroartemisinin varied markedly with respect to that of epimastigotes. C3H/He mice infected with AR-SE23C trypomastigotes had higher levels of parasitemia and mortality rate during the acute phase of infection compared to mice infected with BOL-FC10A trypomastigotes. Treatment of infected mice with benznidazole or nifurtimox was efficient to reduce patent parasitemia induced by either isolate. Nevertheless, qPCR performed at 70 dpi revealed parasite DNA in the blood of mice infected with AR-SE23C but not in BOL-FC10A infected mice. These results demonstrate high level of intra-type diversity which may represent an important obstacle for the testing of chemotherapeutic agents. Fil: Quebrada Palacio, Luz Piedad. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: González, Mariela Natacha. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Hernandez Vasquez, Yolanda Maria. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina Fil: Perrone, Alina Elizabeth. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Parodi Talice, Adriana. Universidad de la República; Uruguay Fil: Bua, Jacqueline Elena. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Postan, Miriam. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina |
| Databáze: | OpenAIRE |
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