{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:34:23Z","timestamp":1791920063270,"version":"4.3.4"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2004,5,1]],"date-time":"2004-05-01T00:00:00Z","timestamp":1083369600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2004,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Resistance to diminazene aceturate (Berenil) is a severe problem in the control of African trypanosomiasis in domestic animals. It has been speculated that resistance may be the result of reduced diminazene uptake by the parasite. We describe here the mechanisms by which [\n            <jats:sup>3<\/jats:sup>\n            H]diminazene is transported by\n            <jats:italic>Trypanosoma brucei brucei<\/jats:italic>\n            bloodstream forms. Diminazene was rapidly accumulated through a single transporter, with a\n            <jats:italic>\n              K\n              <jats:sub>m<\/jats:sub>\n            <\/jats:italic>\n            of 0.45 \u00b1 0.11 \u03bcM, which was dose dependently inhibited by pentamidine and adenosine. The\n            <jats:italic>\n              K\n              <jats:sub>i<\/jats:sub>\n            <\/jats:italic>\n            values for these inhibitors were consistent with this transporter being the P2\/TbAT1 adenosine transporter. Yeast expressing\n            <jats:italic>TbAT1<\/jats:italic>\n            acquired the ability to take up [\n            <jats:sup>3<\/jats:sup>\n            H]diminazene and [\n            <jats:sup>3<\/jats:sup>\n            H]pentamidine.\n            <jats:italic>TbAT1<\/jats:italic>\n            -null mutants had lost almost all capacity for [\n            <jats:sup>3<\/jats:sup>\n            H]diminazene transport. However, this cell line still displayed a small but detectable rate of [\n            <jats:sup>3<\/jats:sup>\n            H]diminazene accumulation, in a nonsaturable manner. We conclude that TbAT1 mediates [\n            <jats:sup>3<\/jats:sup>\n            H]diminazene transport almost exclusively and that this explains the observed diminazene resistance phenotypes of\n            <jats:italic>TbAT1<\/jats:italic>\n            -null mutants and field isolates.\n          <\/jats:p>","DOI":"10.1128\/aac.48.5.1515-1519.2004","type":"journal-article","created":{"date-parts":[[2004,4,22]],"date-time":"2004-04-22T19:58:16Z","timestamp":1082663896000},"page":"1515-1519","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":105,"title":["The Trypanocide Diminazene Aceturate Is Accumulated Predominantly through the TbAT1 Purine Transporter: Additional Insights on Diamidine Resistance in African Trypanosomes"],"prefix":"10.1128","volume":"48","author":[{"given":"Harry P.","family":"de Koning","sequence":"first","affiliation":[{"name":"Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, Glasgow G12 8QQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura F.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, Glasgow G12 8QQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mhairi","family":"Stewart","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, Glasgow G12 8QQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J. S.","family":"Burchmore","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, Glasgow G12 8QQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynsey J. M.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, Glasgow G12 8QQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Barrett","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, Glasgow G12 8QQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0304-4017(00)00427-1","volume":"96","year":"2001","unstructured":"Anene, B. M., D. N. Onah, and Y. Nawa. 2001. Drug resistance in pathogenic African trypanosomes: what hopes for the future? Vet. Parasitol.96:83-100.","journal-title":"Vet. 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