Gene expression study using real-time PCR identifies an NTR gene as a major marker of resistance to benznidazole in Trypanosoma cruzi

dc.creatorMejía Jaramillo, Ana María
dc.creatorFernández García, Geysson Javier
dc.creatorPalacio Muñoz, Lina Marcela
dc.creatorTriana Chávez, Omar
dc.date2021-11-02T16:55:54Z
dc.date2021-11-02T16:55:54Z
dc.date2011
dc.date.accessioned2023-08-28T20:43:33Z
dc.date.available2023-08-28T20:43:33Z
dc.identifierMejía, A., Fernández, G., Palacio, L., & Triana, O. (2011). Gene expression study using real-time PCR identifies an NTR gene as a major marker of resistance to benznidazole in Trypanosoma cruzi. Parasites Vectors. 4; 1-12. https://doi.org/10.1186/1756-3305-4-16
dc.identifierhttp://hdl.handle.net/10495/23695
dc.identifier10.1186/1756-3305-4-169
dc.identifier1756-3305
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8483390
dc.descriptionABSTRACT: Background: Chagas disease is a neglected illness, with limited treatments, caused by the parasite Trypanosoma cruzi. Two drugs are prescribed to treat the disease, nifurtimox and benznidazole, which have been previously reported to have limited efficacy and the appearance of resistance by T. cruzi. Acquisition of drug-resistant phenotypes is a complex physiological process based on single or multiple changes of the genes involved, probably in its mechanisms of action. Results: The differential genes expression of a sensitive Trypanosoma cruzi strain and its induced in vitro benznidazole-resistant phenotypes was studied. The stepwise increasing concentration of BZ in the parental strain generated five different resistant populations assessed by the IC50 ranging from 10.49 to 93.7 μM. The resistant populations maintained their phenotype when the BZ was depleted from the culture for many passages. Additionally, the benznidazole-resistant phenotypes presented a cross-resistance to nifurtimox but not to G418 sulfate. On the other hand, four of the five phenotypes resistant to different concentrations of drugs had different expression levels for the 12 genes evaluated by real-time PCR. However, in the most resistant phenotype (TcR5x), the levels of mRNA from these 12 genes and seven more were similar to the parental strain but not for NTR and OYE genes, which were down-regulated and over-expressed, respectively. The number of copies for these two genes was evaluated for the parental strain and the TcR5x phenotype, revealing that the NTR gene had lost a copy in this last phenotype. No changes were found in the enzyme activity of CPR and SOD in the most resistant population. Finally, there was no variability of genetic profiles among all the parasite populations evaluated by performing low-stringency single-specific primer PCR (LSSP-PCR) and random amplified polymorphic DNA RAPD techniques, indicating that no clonal selection or drastic genetic changes had occurred for the exposure to BZ. Conclusion: Here, we propose NTR as the major marker of the appearance of resistance to BZ.
dc.descriptionCOL0007865
dc.format12
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherBMC
dc.publisherBiología y Control de Enfermedades Infecciosas
dc.publisherLondres, Inglaterra
dc.relationParasit. Vectors.
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://creativecommons.org/licenses/by/2.5/co/
dc.rightshttp://purl.org/coar/access_right/c_abf2
dc.rightshttps://creativecommons.org/licenses/by/4.0/
dc.subjectEnfermedad de chagas
dc.subjectChagas Disease
dc.subjectTrypanosoma cruzi
dc.subjectResistencia a Medicamentos
dc.subjectDrug Resistance
dc.subjectNifurtimox
dc.subjectBenznidazol
dc.titleGene expression study using real-time PCR identifies an NTR gene as a major marker of resistance to benznidazole in Trypanosoma cruzi
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.typehttp://purl.org/coar/resource_type/c_2df8fbb1
dc.typehttps://purl.org/redcol/resource_type/ART
dc.typeArtículo de investigación


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