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

doi: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

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)

Biological Chemistry and Drug Discovery

Research output: Contribution to journal › Article › peer-review

106 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 language	English
Pages (from-to)	651-663
Number of pages	13
Journal	Journal of Antimicrobial Chemotherapy
Volume	69
Issue number	3
Early online date	13 Nov 2013
DOIs	https://doi.org/10.1093/jac/dkt442
Publication status	Published - 1 Mar 2014

Keywords

drug transport
protozoan
parasite
resistance mutation
aquaporin

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10.1093/jac/dkt442

Melarsoprol-Pentamidine Cross Resistance in African Trypanosomes.
Horn, D. (Investigator)
Medical Research Council
28/10/13 → 27/10/16
Project: Research
High-Throughput Decoding of Virulence Mechanisms in African Trypanosomes (Senior Investigator Award)
Horn, D. (Investigator)
1/09/13 → 29/02/20
Project: Research

Cite this

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

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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",

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doi = "10.1093/jac/dkt442",

language = "English",

volume = "69",

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

Research output: Contribution to journal › Article › peer-review

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

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SN - 0305-7453

VL - 69

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JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

IS - 3

ER -

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

Keywords

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Projects

Melarsoprol-Pentamidine Cross Resistance in African Trypanosomes.

High-Throughput Decoding of Virulence Mechanisms in African Trypanosomes (Senior Investigator Award)

Cite this