Two novel nucleobase/pentamidine transporters from Trypanosoma brucei.
African trypanosomes are unable to synthesize purines de novo and must salvage preformed purine nucleosides and nucleobases from their hosts. The Trypanosoma brucei genome project has identified 12 members of the equilibrative nucleoside transporter family, most of which have been characterized previously as nucleoside and/or nucleobase transporters. Here the 11th member of this family, TbNT11.1, has been functionally expressed in null mutants of Leishmania that are deficient in purine nucleoside or nucleobase uptake and identified as a high-affinity purine nucleobase transporter. Expression of TbNT11.1 in Xenopus oocytes revealed that it is also a transporter for the diamidine drug pentamidine that is the principal drug employed to treat early stage human African trypanosomiasis and may thus contribute to the uptake of this therapeutically important compound. In addition, characterization of the 12th member of the family, TbNT12.1, reveals that it is an adenine/pentamidine transporter.
Ortiz
Diana
D
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239, USA.
Sanchez
Marco A
MA
Quecke
Paula
P
Landfear
Scott M
SM
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D007700:Kinetics; D026901:Membrane Transport Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D010419:Pentamidine / Q000378:metabolism*; D015800:Protozoan Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism*
D026901:Membrane Transport Proteins; D015800:Protozoan Proteins; D010419:Pentamidine