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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
International journal for parasitology. Drugs and drug resistance - 5(2015), 2 vom: 01. Aug., Seite 65-8 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Graf, Fabrice E [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.05.2016 Date Revised 10.07.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1016/j.ijpddr.2015.04.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM249645513 |
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| 100 | 1 | |a Graf, Fabrice E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Chimerization at the AQP2-AQP3 locus is the genetic basis of melarsoprol-pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates |
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| 500 | |a Date Revised 10.07.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Aquaporin | |
| 650 | 4 | |a Drug resistance | |
| 650 | 4 | |a Human African trypanosomiasis | |
| 650 | 4 | |a Melarsoprol | |
| 650 | 4 | |a Pentamidine | |
| 650 | 4 | |a Reverse genetics | |
| 650 | 4 | |a Sleeping sickness | |
| 650 | 4 | |a Trypanosoma brucei gambiense | |
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| 650 | 7 | |a Pentamidine |2 NLM | |
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| 700 | 1 | |a Baker, Nicola |e verfasserin |4 aut | |
| 700 | 1 | |a Munday, Jane C |e verfasserin |4 aut | |
| 700 | 1 | |a de Koning, Harry P |e verfasserin |4 aut | |
| 700 | 1 | |a Horn, David |e verfasserin |4 aut | |
| 700 | 1 | |a Mäser, Pascal |e verfasserin |4 aut | |
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