Chimerization at the AQP2-AQP3 locus is the genetic basis of melarsoprol-pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates

Fabrice E. Graf, Nicola Baker, Jane C. Munday, Harry P. de Koning, David Horn, Pascal Mäser (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    30 Citations (Scopus)
    137 Downloads (Pure)

    Abstract

    Aquaglyceroporin-2 is a known determinant of melarsoprol-pentamidine cross-resistance in Trypanosoma brucei brucei laboratory strains. Recently, chimerization at the AQP2-AQP3 tandem locus was described from melarsoprol-pentamidine cross-resistant Trypanosoma brucei gambiense isolates from sleeping sickness patients in the Democratic Republic of the Congo. Here, we demonstrate that reintroduction of wild-type AQP2 into one of these isolates fully restores drug susceptibility while expression of the chimeric AQP2/3 gene in aqp2-aqp3 null T. b. brucei does not. This proves that AQP2-AQP3 chimerization is the cause of melarsoprol-pentamidine cross-resistance in the T. b. gambiense isolates.

    Original languageEnglish
    Pages (from-to)65-68
    Number of pages4
    JournalInternational Journal for Parasitology: Drugs and Drug Resistance
    Volume5
    Issue number2
    DOIs
    Publication statusPublished - Aug 2015

    Keywords

    • Aquaporin
    • Drug resistance
    • Human African trypanosomiasis
    • Melarsoprol
    • Pentamidine
    • Reverse genetics
    • Sleeping sickness
    • Trypanosoma brucei gambiense

    Fingerprint Dive into the research topics of 'Chimerization at the AQP2-AQP3 locus is the genetic basis of melarsoprol-pentamidine cross-resistance in clinical <i>Trypanosoma brucei gambiense</i> isolates'. Together they form a unique fingerprint.

  • Projects

    Cite this