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Int J Parasitol Drugs Drug Resist. 2015 May 7;5(2):65-8. doi: 10.1016/j.ijpddr.2015.04.002. eCollection 2015 Aug.

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

Author information

1
Swiss Tropical and Public Health Institute, CH-4051 Basel, Switzerland ; University of Basel, CH-4000 Basel, Switzerland.
2
Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
3
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12 8TA, UK.

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

PMID:
26042196
PMCID:
PMC4443405
DOI:
10.1016/j.ijpddr.2015.04.002
[Indexed for MEDLINE]
Free PMC Article

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