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

Graf, F. E., Baker, N., Munday, J. C. , De Koning, H. P. , Horn, D. and Mäser, P. (2015) Chimerization at the AQP2–AQP3 locus is the genetic basis of melarsoprol–pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates. International Journal for Parasitology: Drugs and Drug Resistance, 5(2), pp. 65-68. (doi: 10.1016/j.ijpddr.2015.04.002) (PMID:26042196) (PMCID:PMC4443405)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Munday, Dr Jane and De Koning, Professor Harry
• Authors: Graf, F. E., Baker, N., Munday, J. C., De Koning, H. P., Horn, D., and Mäser, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: International Journal for Parasitology: Drugs and Drug Resistance
• Publisher: Elsevier Ltd.
• ISSN: 2211-3207
• ISSN (Online): 2211-3207
• Copyright Holders: Copyright © 2015 The Authors
• First Published: First published in the International Journal for Parasitology: Drugs and Drug Resistance 5(2):65-68
• Publisher Policy: Reproduced under a Creative Commons License