Trypanosoma brucei: a survey of pyrimidine transport activities

Experimental Parasitology
Simon GudinHarry P de Koning

Abstract

Purine uptake has been studied in many protozoan parasites in the last few years, and several of the purine transporters have been cloned. In contrast, very little is known about the salvage of preformed pyrimidines by protozoa, and no pyrimidine transporters have been cloned, yet chemotherapy based on pyrimidine nucleobases and nucleosides has been as effective as purine antimetabolites in the treatment of infectious and neoplastic disease. Here, we surveyed the presence of pyrimidine transporters in Trypanosoma brucei brucei. We could not detect any mediated uptake of thymine, thymidine or cytidine, but identified a very high-affinity transporter for cytosine, designated C1, with a K(m) value of 0.048+/-0.009 microM. We also confirmed the presence of the previously reported U1 uracil transporter and found it capable of mediating uridine uptake as well, with a K(m) of 33+/-5 microM. A higher-affinity U2 uridine transporter (K(m)=4.1+/-2.1 microM) was also identified, but efficiency of the C1 and U2-mediated transport was low. Pyrimidine antimetabolites were tested as potential trypanocidal agents and only 5-fluorouracil was found to be effective. This drug was efficiently taken up by bloodstream forms of T. b. brucei.

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Citations

Nov 28, 2013·PLoS Neglected Tropical Diseases·Jean-François RittMarc Ouellette
May 1, 2009·Future Medicinal Chemistry·Meryem Köse, Anke C Schiedel
Dec 1, 2009·Experimental Parasitology·Jana M SimmonsRobert P Hausinger
Jul 29, 2008·The International Journal of Biochemistry & Cell Biology·Víctor M Castillo-AcostaDolores González-Pacanowska
Mar 22, 2007·Trends in Parasitology·Vivian Bellofatto
Dec 21, 2007·Proteomics·Daniel J BridgesRichard J S Burchmore
Oct 23, 2015·Metabolomics : Official Journal of the Metabolomic Society·Dong-Hyun KimMichael P Barrett
Dec 4, 2012·Molecular and Biochemical Parasitology·Víctor M Castillo-AcostaDolores González-Pacanowska
Feb 10, 2018·Parasites & Vectors·Kartikeya Tiwari, Vikash Kumar Dubey
Mar 8, 2020·Medicinal Research Reviews·Gustavo D Campagnaro, Harry P de Koning
Aug 8, 2019·Scientific Reports·Abdullah AlotaibiDavid G Watson

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