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

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...

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Autores principales: Graf, Fabrice E., Baker, Nicola, Munday, Jane C., de Koning, Harry P., Horn, David, Mäser, Pascal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Brief Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443405/
https://www.ncbi.nlm.nih.gov/pubmed/26042196
http://dx.doi.org/10.1016/j.ijpddr.2015.04.002
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author Graf, Fabrice E.
Baker, Nicola
Munday, Jane C.
de Koning, Harry P.
Horn, David
Mäser, Pascal
author_facet Graf, Fabrice E.
Baker, Nicola
Munday, Jane C.
de Koning, Harry P.
Horn, David
Mäser, Pascal
author_sort Graf, Fabrice E.
collection PubMed
description 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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spelling pubmed-44434052015-06-03 Chimerization at the AQP2–AQP3 locus is the genetic basis of melarsoprol–pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates Graf, Fabrice E. Baker, Nicola Munday, Jane C. de Koning, Harry P. Horn, David Mäser, Pascal Int J Parasitol Drugs Drug Resist Brief Report 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. Elsevier 2015-05-07 /pmc/articles/PMC4443405/ /pubmed/26042196 http://dx.doi.org/10.1016/j.ijpddr.2015.04.002 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Graf, Fabrice E.
Baker, Nicola
Munday, Jane C.
de Koning, Harry P.
Horn, David
Mäser, Pascal
Chimerization at the AQP2–AQP3 locus is the genetic basis of melarsoprol–pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates
title Chimerization at the AQP2–AQP3 locus is the genetic basis of melarsoprol–pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates
title_full Chimerization at the AQP2–AQP3 locus is the genetic basis of melarsoprol–pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates
title_fullStr Chimerization at the AQP2–AQP3 locus is the genetic basis of melarsoprol–pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates
title_full_unstemmed Chimerization at the AQP2–AQP3 locus is the genetic basis of melarsoprol–pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates
title_short Chimerization at the AQP2–AQP3 locus is the genetic basis of melarsoprol–pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates
title_sort chimerization at the aqp2–aqp3 locus is the genetic basis of melarsoprol–pentamidine cross-resistance in clinical trypanosoma brucei gambiense isolates
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443405/
https://www.ncbi.nlm.nih.gov/pubmed/26042196
http://dx.doi.org/10.1016/j.ijpddr.2015.04.002
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