Trypanosoma brucei aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs

Jane C. Munday, Anthonius A Eze, Nicola Baker, Lucy Glover, Caroline Clucas, David Aguinaga Andrés, Manal J Natto, Ibrahim A Teka, Jennifer McDonald, Rebecca S Lee, Fabrice E Graf, Philipp Ludin, Richard J S Burchmore, C Michael R. Turner, Andy Tait, Annette MacLeod, Pascal Mäser, Michael P. Barrett, David Horn, Harry P. De Koning (Lead / Corresponding author)

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Abstract

Trypanosoma brucei drug transporters include the TbAT1/P2 aminopurine transporter and the high-affinity pentamidine transporter (HAPT1), but the genetic identity of HAPT1 is unknown. We recently reported that loss of T. brucei aquaglyceroporin 2 (TbAQP2) caused melarsoprol/pentamidine cross-resistance (MPXR) in these parasites and the current study aims to delineate the mechanism by which this occurs.
Original languageEnglish
Pages (from-to)651-663
Number of pages13
JournalJournal of Antimicrobial Chemotherapy
Volume69
Issue number3
Early online date13 Nov 2013
DOIs
Publication statusPublished - 1 Mar 2014

Keywords

  • drug transport
  • protozoan
  • parasite
  • resistance mutation
  • aquaporin

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    Munday, J. C., Eze, A. A., Baker, N., Glover, L., Clucas, C., Andrés, D. A., Natto, M. J., Teka, I. A., McDonald, J., Lee, R. S., Graf, F. E., Ludin, P., Burchmore, R. J. S., Turner, C. M. R., Tait, A., MacLeod, A., Mäser, P., Barrett, M. P., Horn, D., & De Koning, H. P. (2014). Trypanosoma brucei aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs. Journal of Antimicrobial Chemotherapy, 69(3), 651-663. https://doi.org/10.1093/jac/dkt442