Journal
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
Volume 5, Issue 2, Pages 65-68Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ijpddr.2015.04.002
Keywords
Human African trypanosomiasis; Sleeping sickness; Trypanosoma brucei gambiense; Drug resistance; Melarsoprol; Pentamidine; Aquaporin; Reverse genetics
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Funding
- Swiss National Science Foundation [31003A_135746]
- UK Medical Research Council (MRC) [84733]
- MRC
- Department for International Development, UK under the MRC/DFID Concordat agreement [MR/K000500/1]
- Wellcome Trust [100320/Z/12/Z]
- MRC [G0701258, MR/K000500/1] Funding Source: UKRI
- Medical Research Council [G0701258, MR/K000500/1] Funding Source: researchfish
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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 wildtype 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. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology.
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