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A Nucleoside Transporter from Trypanosoma brucei Involved in Drug Resistance

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Science  09 Jul 1999:
Vol. 285, Issue 5425, pp. 242-244
DOI: 10.1126/science.285.5425.242

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Abstract

Drug resistance of pathogens is an increasing problem whose underlying mechanisms are not fully understood. Cellular uptake of the major drugs against Trypanosoma brucei spp., the causative agents of sleeping sickness, is thought to occur through an unusual, so far unidentified adenosine transporter. Saccharomyces cerevisiaewas used in a functional screen to clone a gene (TbAT1) from Trypanosoma brucei brucei that encodes a nucleoside transporter. When expressed in yeast,TbAT1 enabled adenosine uptake and conferred susceptibility to melaminophenyl arsenicals. Drug-resistant trypanosomes harbor a defective TbAT1 variant. The molecular identification of the entry route of trypanocides opens the way to approaches for diagnosis and treatment of drug-resistant sleeping sickness.

  • * Present address: Department of Biology, University of California, San Diego, La Jolla, CA 92093, USA.

  • Present address: Novartis CRA, CH-1566 St. Aubin, Switzerland.

  • To whom correspondence should be addressed. E-mail: ronald.kaminsky{at}ah.novartis.com

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