Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story

Nicola Baker, Harry P. de Koning, Pascal Maeser, David Horn

    Research output: Contribution to journalReview articlepeer-review

    137 Citations (Scopus)

    Abstract

    Melarsoprol and pentamidine represent the two main classes of drugs, the arsenicals and diamidines, historically used to treat the diseases caused by African trypanosomes: sleeping sickness in humans and Nagana in livestock. Cross-resistance to these drugs was first observed over 60 years ago and remains the only example of cross-resistance among sleeping sickness therapies. A Trypanosome brucei adenosine transporter is well known for its role in the uptake of both drugs. More recently, aquaglyceroporin 2 (AQP2) loss of function was linked to melarsoprol-pentamidine cross-resistance. AQP2, a channel that appears to facilitate drug accumulation, may also be linked to clinical cases of resistance. Here, we review these findings and consider some new questions as well as future prospects for tackling the devastating diseases caused by these parasites. 'Cellular therapy is a consequence of cellular nutrition, for only those compounds can affect the cell that are actually eaten by it.' - Paul Ehrlich, 1907 [1].

    Original languageEnglish
    Pages (from-to)110-118
    Number of pages9
    JournalTrends in Parasitology
    Volume29
    Issue number3
    Early online date30 Jan 2013
    DOIs
    Publication statusPublished - Mar 2013

    Keywords

    • BRUCEI-GAMBIENSE TRYPANOSOMIASIS
    • AT1
    • ABC TRANSPORTERS
    • P2 ADENOSINE TRANSPORTER
    • COMBINATION THERAPY
    • MRPA
    • CROSS-RESISTANCE
    • AQP2
    • MIP
    • SLEEPING SICKNESS
    • NUCLEOSIDE TRANSPORTER
    • MULTIDRUG-RESISTANCE
    • drug resistance
    • 3 AQUAGLYCEROPORINS
    • Trypanosoma brucei
    • BLOOD-STREAM FORM

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