{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:51:31Z","timestamp":1773813091801,"version":"3.50.1"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2010,2,1]],"date-time":"2010-02-01T00:00:00Z","timestamp":1264982400000},"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":["Eukaryot Cell"],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The P2 aminopurine transporter, encoded by Tb\n            <jats:italic>AT1<\/jats:italic>\n            in African trypanosomes in the\n            <jats:named-content content-type=\"genus-species\">Trypanosoma brucei<\/jats:named-content>\n            group, carries melaminophenyl arsenical and diamidine drugs into these parasites. Loss of this transporter contributes to drug resistance. We identified the genomic location of Tb\n            <jats:italic>AT1<\/jats:italic>\n            to be in the subtelomeric region of chromosome 5 and determined the status of the Tb\n            <jats:italic>AT1<\/jats:italic>\n            gene in two trypanosome lines selected for resistance to the melaminophenyl arsenical, melarsamine hydrochloride (Cymelarsan), and in a\n            <jats:named-content content-type=\"genus-species\">Trypanosoma equiperdum<\/jats:named-content>\n            clone selected for resistance to the diamidine, diminazene aceturate. In the\n            <jats:named-content content-type=\"genus-species\">Trypanosoma brucei<\/jats:named-content>\n            <jats:named-content content-type=\"genus-species\">gambiense<\/jats:named-content>\n            STIB 386 melarsamine hydrochloride-resistant line, Tb\n            <jats:italic>AT1<\/jats:italic>\n            is deleted, while in the\n            <jats:named-content content-type=\"genus-species\">Trypanosoma brucei brucei<\/jats:named-content>\n            STIB 247 melarsamine hydrochloride-resistant and\n            <jats:named-content content-type=\"genus-species\">T. equiperdum<\/jats:named-content>\n            diminazene-resistant lines, Tb\n            <jats:italic>AT1<\/jats:italic>\n            is present, but expression at the RNA level is no longer detectable. Further characterization of Tb\n            <jats:italic>AT1<\/jats:italic>\n            in\n            <jats:named-content content-type=\"genus-species\">T. equiperdum<\/jats:named-content>\n            revealed that a loss of heterozygosity at the Tb\n            <jats:italic>AT1<\/jats:italic>\n            locus accompanied loss of expression and that P2-mediated uptake of [\n            <jats:sup>3<\/jats:sup>\n            H]diminazene is lost in drug-resistant\n            <jats:named-content content-type=\"genus-species\">T. equiperdum<\/jats:named-content>\n            . Adenine-inhibitable adenosine uptake is still detectable in a \u0394Tb\n            <jats:italic>at1<\/jats:italic>\n            <jats:named-content content-type=\"genus-species\">T. b. brucei<\/jats:named-content>\n            mutant, although at a greatly reduced capacity compared to that of the wild type, indicating that an additional adenine-inhibitable adenosine permease, distinct from P2, is present in these cells.\n          <\/jats:p>","DOI":"10.1128\/ec.00200-09","type":"journal-article","created":{"date-parts":[[2009,12,5]],"date-time":"2009-12-05T04:39:23Z","timestamp":1259987963000},"page":"336-343","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Multiple Genetic Mechanisms Lead to Loss of Functional TbAT1 Expression in Drug-Resistant Trypanosomes"],"prefix":"10.1128","volume":"9","author":[{"given":"Mhairi L.","family":"Stewart","sequence":"first","affiliation":[{"name":"Division of Infection &amp; Immunity, FBLS, University of Glasgow, Glasgow, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J. S.","family":"Burchmore","sequence":"additional","affiliation":[{"name":"Division of Infection &amp; Immunity, FBLS, University of Glasgow, Glasgow, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Clucas","sequence":"additional","affiliation":[{"name":"Wellcome Centre of Molecular Parasitology, University of Glasgow, Glasgow, United Kingdom; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiane","family":"Hertz-Fowler","sequence":"additional","affiliation":[{"name":"Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Brooks","sequence":"additional","affiliation":[{"name":"Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Tait","sequence":"additional","affiliation":[{"name":"Wellcome Centre of Molecular Parasitology, University of Glasgow, Glasgow, United Kingdom; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"MacLeod","sequence":"additional","affiliation":[{"name":"Wellcome Centre of Molecular Parasitology, University of Glasgow, Glasgow, United Kingdom; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. Michael R.","family":"Turner","sequence":"additional","affiliation":[{"name":"Division of Infection &amp; Immunity, FBLS, University of Glasgow, Glasgow, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry P.","family":"De Koning","sequence":"additional","affiliation":[{"name":"Division of Infection &amp; Immunity, FBLS, University of Glasgow, Glasgow, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pui Ee","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Infection &amp; Immunity, FBLS, University of Glasgow, Glasgow, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"Barrett","sequence":"additional","affiliation":[{"name":"Division of Infection &amp; Immunity, FBLS, University of Glasgow, Glasgow, United Kingdom;"},{"name":"Wellcome Centre of Molecular Parasitology, University of Glasgow, Glasgow, United Kingdom; and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707354"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14694-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(95)00120-P"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.2955304"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07292.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112642"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/4.2.124"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/23.24.4992"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.031351"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.47.28153"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/361173a0"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti553"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2006.11.003"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.59.3.586"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.5.1515-1519.2004"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.15.3017"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/322173a0"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.024653"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(96)02810-1"},{"key":"e_1_3_2_21_2","volume-title":"Molecular cloning: a laboratory manual","author":"Maniatis T.","year":"1982","unstructured":"Maniatis T. 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