• Login
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population. 
    •   QMRO Home
    • School of Biological and Chemical Sciences
    • Cell and Molecular Biology
    • Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population.
    •   QMRO Home
    • School of Biological and Chemical Sciences
    • Cell and Molecular Biology
    • Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population.
    ‌
    ‌

    Browse

    All of QMROCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    ‌
    ‌

    Administrators only

    Login
    ‌
    ‌

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population.

    View/Open
    Accepted version (735.3Kb)
    Volume
    206
    Pagination
    220 - 228
    DOI
    10.1093/infdis/jis331
    Journal
    J Infect Dis
    Issue
    2
    Metadata
    Show full item record
    Abstract
    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 parasites, all clones examined had lost one of the chromosomes containing the TcNTR gene. Sequence analysis of the remaining TcNTR allele revealed 3 distinct mutant genes in different resistant clones. Expression studies showed that these mutant proteins were unable to activate benznidazole. This correlated with loss of flavin mononucleotide binding. The drug-resistant phenotype could be reversed by transfection with wild-type TcNTR. These results identify TcNTR as a central player in acquired resistance to benznidazole. They also demonstrate that T. cruzi has a propensity to undergo genetic changes that can lead to drug resistance, a finding that has implications for future therapeutic strategies.
    Authors
    Mejia, AM; Hall, BS; Taylor, MC; Gómez-Palacio, A; Wilkinson, SR; Triana-Chávez, O; Kelly, JM
    URI
    http://qmro.qmul.ac.uk/xmlui/handle/123456789/12389
    Collections
    • Cell and Molecular Biology [192]
    Language
    eng
    Licence information
    © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Twitter iconFollow QMUL on Twitter
    Twitter iconFollow QM Research
    Online on twitter
    Facebook iconLike us on Facebook
    • Site Map
    • Privacy and cookies
    • Disclaimer
    • Accessibility
    • Contacts
    • Intranet
    • Current students

    Modern Slavery Statement

    Queen Mary University of London
    Mile End Road
    London E1 4NS
    Tel: +44 (0)20 7882 5555

    © Queen Mary University of London.