chimerization at the aqp2–aqp3 locus is the genetic basis of melarsoprol–pentamidine cross-resistance in clinical trypanosoma brucei gambiense isolates

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ID: 147591
2015
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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.
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Authors ;Fabrice E. Graf;Nicola Baker;Jane C. Munday;Harry P. de Koning;David Horn;Pascal Mäser
Journal deutsche zeitschrift fur philosophie
Year 2015
DOI
10.1016/j.ijpddr.2015.04.002
URL
http://www.sciencedirect.com/science/article/pii/S2211320715000081
Keywords
Drug resistance trypanosoma brucei gambiense aquaporin sleeping sickness

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