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)

Research output: Contribution to journalArticle

63 Citations (Scopus)

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

Fingerprint

Aquaglyceroporins
Pentamidine
Trypanosoma brucei brucei
Arsenic
Drug Resistance
Melarsoprol
Pedigree
Pharmaceutical Preparations
Parasites

Keywords

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

Cite this

Munday, Jane C. ; Eze, Anthonius A ; Baker, Nicola ; Glover, Lucy ; Clucas, Caroline ; Andrés, David Aguinaga ; Natto, Manal J ; Teka, Ibrahim A ; McDonald, Jennifer ; Lee, Rebecca S ; Graf, Fabrice E ; Ludin, Philipp ; Burchmore, Richard J S ; Turner, C Michael R. ; Tait, Andy ; MacLeod, Annette ; Mäser, Pascal ; Barrett, Michael P. ; Horn, David ; De Koning, Harry P. / 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. In: Journal of Antimicrobial Chemotherapy. 2014 ; Vol. 69, No. 3. pp. 651-663.
@article{787134d9b02e454383b8a4db44e6b56f,
title = "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",
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.",
keywords = "drug transport, protozoan, parasite, resistance mutation, aquaporin",
author = "Munday, {Jane C.} and Eze, {Anthonius A} and Nicola Baker and Lucy Glover and Caroline Clucas and Andr{\'e}s, {David Aguinaga} and Natto, {Manal J} and Teka, {Ibrahim A} and Jennifer McDonald and Lee, {Rebecca S} and Graf, {Fabrice E} and Philipp Ludin and Burchmore, {Richard J S} and Turner, {C Michael R.} and Andy Tait and Annette MacLeod and Pascal M{\"a}ser and Barrett, {Michael P.} and David Horn and {De Koning}, {Harry P.}",
year = "2014",
month = "3",
day = "1",
doi = "10.1093/jac/dkt442",
language = "English",
volume = "69",
pages = "651--663",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "3",

}

Munday, JC, Eze, AA, Baker, N, Glover, L, Clucas, C, Andrés, DA, Natto, MJ, Teka, IA, McDonald, J, Lee, RS, Graf, FE, Ludin, P, Burchmore, RJS, Turner, CMR, Tait, A, MacLeod, A, Mäser, P, Barrett, MP, Horn, D & De Koning, HP 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, vol. 69, no. 3, pp. 651-663. https://doi.org/10.1093/jac/dkt442

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

In: Journal of Antimicrobial Chemotherapy, Vol. 69, No. 3, 01.03.2014, p. 651-663.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Munday, Jane C.

AU - Eze, Anthonius A

AU - Baker, Nicola

AU - Glover, Lucy

AU - Clucas, Caroline

AU - Andrés, David Aguinaga

AU - Natto, Manal J

AU - Teka, Ibrahim A

AU - McDonald, Jennifer

AU - Lee, Rebecca S

AU - Graf, Fabrice E

AU - Ludin, Philipp

AU - Burchmore, Richard J S

AU - Turner, C Michael R.

AU - Tait, Andy

AU - MacLeod, Annette

AU - Mäser, Pascal

AU - Barrett, Michael P.

AU - Horn, David

AU - De Koning, Harry P.

PY - 2014/3/1

Y1 - 2014/3/1

N2 - 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.

AB - 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.

KW - drug transport

KW - protozoan

KW - parasite

KW - resistance mutation

KW - aquaporin

U2 - 10.1093/jac/dkt442

DO - 10.1093/jac/dkt442

M3 - Article

C2 - 24235095

VL - 69

SP - 651

EP - 663

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 3

ER -