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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Detalles Bibliográficos
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
Descripción
Sumario: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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