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

    26 Citations (Scopus)
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    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

    Fingerprint

    Melarsoprol
    Trypanosoma brucei gambiense
    Pentamidine
    Genetic Loci
    Aquaglyceroporins
    Democratic Republic of the Congo
    Trypanosoma brucei brucei
    Pharmaceutical Preparations
    Genes

    Keywords

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

    Cite this

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    title = "Chimerization at the AQP2-AQP3 locus is the genetic basis of melarsoprol-pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates",
    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.",
    keywords = "Aquaporin, Drug resistance, Human African trypanosomiasis, Melarsoprol, Pentamidine, Reverse genetics, Sleeping sickness, Trypanosoma brucei gambiense",
    author = "Graf, {Fabrice E.} and Nicola Baker and Munday, {Jane C.} and {de Koning}, {Harry P.} and David Horn and Pascal M{\"a}ser",
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    Chimerization at the AQP2-AQP3 locus is the genetic basis of melarsoprol-pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates. / Graf, Fabrice E.; Baker, Nicola; Munday, Jane C.; de Koning, Harry P.; Horn, David; Mäser, Pascal (Lead / Corresponding author).

    In: International Journal for Parasitology: Drugs and Drug Resistance, Vol. 5, No. 2, 08.2015, p. 65-68.

    Research output: Contribution to journalArticle

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    AU - Graf, Fabrice E.

    AU - Baker, Nicola

    AU - Munday, Jane C.

    AU - de Koning, Harry P.

    AU - Horn, David

    AU - Mäser, Pascal

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