{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:11:55Z","timestamp":1791259915670,"version":"4.1.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2013,10,10]],"date-time":"2013-10-10T00:00:00Z","timestamp":1381363200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0002475","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T12:11:57Z","timestamp":1381493517000},"page":"e2475","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":78,"title":["Aquaporin 2 Mutations in Trypanosoma brucei gambiense Field Isolates Correlate with Decreased Susceptibility to Pentamidine and Melarsoprol"],"prefix":"10.1371","volume":"7","author":[{"given":"Fabrice E.","family":"Graf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Ludin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Wenzler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Kaiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reto","family":"Brun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patient Pati","family":"Pyana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"B\u00fcscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry P.","family":"de Koning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Horn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"M\u00e4ser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,10,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S0140-6736(09)60829-1","article-title":"Human African trypanosomiasis","volume":"375","author":"R Brun","year":"2010","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/ana.21429","article-title":"The continuing problem of human African trypanosomiasis (sleeping sickness)","volume":"64","author":"PGE Kennedy","year":"2008","journal-title":"Ann Neurol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"e923","DOI":"10.1371\/journal.pntd.0000923","article-title":"Fexinidazole\u2013a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness","volume":"4","author":"E Torreele","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"5602","DOI":"10.1128\/AAC.00246-11","article-title":"Antitrypanosomal activity of fexinidazole, a new oral nitroimidazole drug candidate for treatment of sleeping sickness","volume":"55","author":"M Kaiser","year":"2011","journal-title":"Antimicrob Agents Chemother"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"4379","DOI":"10.1128\/AAC.00498-10","article-title":"Discovery of novel orally bioavailable oxaborole 6-carboxamides that demonstrate cure in a murine model of late-stage central nervous system african trypanosomiasis","volume":"54","author":"B Nare","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"e1151","DOI":"10.1371\/journal.pntd.0001151","article-title":"SCYX-7158, an orally-active benzoxaborole for the treatment of stage 2 human African trypanosomiasis","volume":"5","author":"RT Jacobs","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.coph.2012.05.001","article-title":"Antiparasitic agents: new drugs on the horizon","volume":"12","author":"P M\u00e4ser","year":"2012","journal-title":"Curr Opin Pharmacol"},{"key":"ref8","article-title":"Chemotherapeutische trypanosomen-studien","volume":"44","author":"P Ehrlich","year":"1907","journal-title":"Berl Klin Wochenzeitschrift"},{"key":"ref9","first-page":"123","article-title":"Studies on Chemotherapeutic Action I. the Absorption of Arsenical Compounds and Tartar Emetic by Normal and Resistant Trypanosomes and Its Relation to Drugresistance","volume":"59","author":"F Hawking","year":"1937","journal-title":"J Pharmacol Exp Ther"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0166-6851(87)90142-3","article-title":"Flow cytofluorimetric analysis of drug accumulation by multidrug-resistant Trypanosoma brucei brucei and T. b. rhodesiense","volume":"26","author":"TO Frommel","year":"1987","journal-title":"Mol Biochem Parasitol"},{"key":"ref11","first-page":"281","article-title":"Drug transport and drug resistance in African trypanosomes","volume":"6","author":"P M\u00e4ser","year":"2003","journal-title":"Drug Resist Updat Rev Comment Antimicrob Anticancer Chemother"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"e1001204","DOI":"10.1371\/journal.ppat.1001204","article-title":"A molecular mechanism for eflornithine resistance in African trypanosomes","volume":"6","author":"IM Vincent","year":"2010","journal-title":"PLoS Pathog"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.molbiopara.2010.11.010","article-title":"Genome-wide RNAi screens in African trypanosomes identify the nifurtimox activator NTR and the eflornithine transporter AAT6","volume":"176","author":"N Baker","year":"2011","journal-title":"Mol Biochem Parasitol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.molbiopara.2010.09.002","article-title":"Genome-wide RNAi screens in bloodstream form trypanosomes identify drug transporters","volume":"175","author":"G Schumann Burkard","year":"2011","journal-title":"Mol Biochem Parasitol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/167147a0","article-title":"Acquired resistance to \u201cMelarsen\u201d, tryparsamide and amidines in pathogenic trypanosomes after treatment with \u201cMelarsen\u201d alone","volume":"167","author":"IM ROLLO","year":"1951","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.pt.2008.04.006","article-title":"Ever-increasing complexities of diamidine and arsenical crossresistance in African trypanosomes","volume":"24","author":"HP De Koning","year":"2008","journal-title":"Trends Parasitol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/361173a0","article-title":"Arsenical-resistant trypanosomes lack an unusual adenosine transporter","volume":"361","author":"NS Carter","year":"1993","journal-title":"Nature"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"28153","DOI":"10.1074\/jbc.270.47.28153","article-title":"Uptake of diamidine drugs by the P2 nucleoside transporter in melarsen-sensitive and -resistant Trypanosoma brucei brucei","volume":"270","author":"NS Carter","year":"1995","journal-title":"J Biol Chem"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1126\/science.285.5425.242","article-title":"A nucleoside transporter from Trypanosoma brucei involved in drug resistance","volume":"285","author":"P M\u00e4ser","year":"1999","journal-title":"Science"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1128\/EC.2.5.1003-1008.2003","article-title":"Mechanisms of arsenical and diamidine uptake and resistance in Trypanosoma brucei","volume":"2","author":"E Matovu","year":"2003","journal-title":"Eukaryot Cell"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1124\/mol.106.031351","article-title":"Loss of the high-affinity pentamidine transporter is responsible for high levels of cross-resistance between arsenical and diamidine drugs in African trypanosomes","volume":"71","author":"DJ Bridges","year":"2007","journal-title":"Mol Pharmacol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1124\/mol.59.3.586","article-title":"Uptake of pentamidine in Trypanosoma brucei brucei is mediated by three distinct transporters: implications for cross-resistance with arsenicals","volume":"59","author":"HP De Koning","year":"2001","journal-title":"Mol Pharmacol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/nature10771","article-title":"High-throughput decoding of antitrypanosomal drug efficacy and resistance","volume":"482","author":"S Alsford","year":"2012","journal-title":"Nature"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"10996","DOI":"10.1073\/pnas.1202885109","article-title":"Aquaglyceroporin 2 controls susceptibility to melarsoprol and pentamidine in African trypanosomes","volume":"109","author":"N Baker","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"42669","DOI":"10.1074\/jbc.M404518200","article-title":"Cloning, heterologous expression, and characterization of three aquaglyceroporins from Trypanosoma brucei","volume":"279","author":"NL Uzcategui","year":"2004","journal-title":"J Biol Chem"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1159\/000327968","article-title":"Functional characterization of three aquaglyceroporins from Trypanosoma brucei in osmoregulation and glycerol transport","volume":"27","author":"B Bassarak","year":"2011","journal-title":"Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"6053","DOI":"10.1073\/pnas.092131899","article-title":"Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9","volume":"99","author":"Z Liu","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"31010","DOI":"10.1074\/jbc.M403959200","article-title":"Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin","volume":"279","author":"B Gourbal","year":"2004","journal-title":"J Biol Chem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"e658","DOI":"10.1371\/journal.pntd.0000658","article-title":"The genome sequence of Trypanosoma brucei gambiense, causative agent of chronic human african trypanosomiasis","volume":"4","author":"AP Jackson","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1126\/science.1112642","article-title":"The genome of the African trypanosome Trypanosoma brucei","volume":"309","author":"M Berriman","year":"2005","journal-title":"Science"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.pt.2012.12.005","article-title":"Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story","volume":"29","author":"N Baker","year":"2013","journal-title":"Trends Parasitol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1128\/EC.00200-09","article-title":"Multiple genetic mechanisms lead to loss of functional TbAT1 expression in drug-resistant trypanosomes","volume":"9","author":"ML Stewart","year":"2010","journal-title":"Eukaryot Cell"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0166-6851(01)00332-2","article-title":"Genetic variants of the TbAT1 adenosine transporter from African trypanosomes in relapse infections following melarsoprol therapy","volume":"117","author":"E Matovu","year":"2001","journal-title":"Mol Biochem Parasitol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1111\/j.1365-3156.2007.01918.x","article-title":"Detection of mutant P2 adenosine transporter (TbAT1) gene in Trypanosoma brucei gambiense isolates from northwest Uganda using allele-specific polymerase chain reaction","volume":"12","author":"B Nerima","year":"2007","journal-title":"Trop Med Int Heal TM IH"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.actatropica.2007.07.007","article-title":"Genotypic and phenotypic characterization of Trypanosoma brucei gambiense isolates from Ibba, South Sudan, an area of high melarsoprol treatment failure rate","volume":"104","author":"N Maina","year":"2007","journal-title":"Acta Trop"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"e523","DOI":"10.1371\/journal.pntd.0000523","article-title":"Genotypic status of the TbAT1\/P2 adenosine transporter of Trypanosoma brucei gambiense isolates from Northwestern Uganda following melarsoprol withdrawal","volume":"3","author":"AJN Kazibwe","year":"2009","journal-title":"PLoS Negl Trop Dis"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"e1025","DOI":"10.1371\/journal.pntd.0001025","article-title":"Isolation of Trypanosoma brucei gambiense from cured and relapsed sleeping sickness patients and adaptation to laboratory mice","volume":"5","author":"PP Pyana","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1002\/j.1460-2075.1985.tb03772.x","article-title":"Cultivation in a semi-defined medium of animal infective forms of Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense","volume":"4","author":"T Baltz","year":"1985","journal-title":"EMBO J"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"985","DOI":"10.2307\/3282883","article-title":"Continuous cultivation of Trypanosoma brucei blood stream forms in a medium containing a low concentration of serum protein without feeder cell layers","volume":"75","author":"H Hirumi","year":"1989","journal-title":"J Parasitol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0001-706X(97)00079-X","article-title":"The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T.b. rhodesiense and T.b. gambiense) in vitro","volume":"68","author":"B R\u00e4z","year":"1997","journal-title":"Acta Trop"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0014-4894(89)90074-X","article-title":"Trypanosoma brucei brucei: expression of drug resistance in vitro","volume":"69","author":"R Kaminsky","year":"1989","journal-title":"Exp Parasitol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/BF00931271","article-title":"Efficacy of experimental trypanocidal compounds against a multiple drug-resistant Trypanosoma brucei brucei stock in mice","volume":"75","author":"E Zweygarth","year":"1989","journal-title":"Parasitol Res"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"D362","DOI":"10.1093\/nar\/gkr914","article-title":"MIPModDB: a central resource for the superfamily of major intrinsic proteins","volume":"40","author":"AB Gupta","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1128\/AAC.48.5.1515-1519.2004","article-title":"The trypanocide diminazene aceturate is accumulated predominantly through the TbAT1 purine transporter: additional insights on diamidine resistance in african trypanosomes","volume":"48","author":"HP De Koning","year":"2004","journal-title":"Antimicrob Agents Chemother"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1124\/mol.111.071555","article-title":"The diamidine diminazene aceturate is a substrate for the high-affinity pentamidine transporter: implications for the development of high resistance levels in trypanosomes","volume":"80","author":"IA Teka","year":"2011","journal-title":"Mol Pharmacol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ijpddr.2013.01.004","article-title":"Functional expression of TcoAT1 reveals it to be a P1-type nucleoside transporter with no capacity for diminazene uptake","volume":"3","author":"JC Munday","year":"2013","journal-title":"Int J Parasitol Drugs Drug Resist"},{"key":"ref47","doi-asserted-by":"crossref","unstructured":"Burri C, Stich A, Brun R (2004) Chemotherapy of Human African Trypanosomiasis. In: Maudlin I, Holmes PH, Miles MA, editors. The Trypanosomiasis. Wallingford, UK; Cambridge, MA, USA: CABI Pub. pp. 403\u2013419.","DOI":"10.1079\/9780851994758.0403"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1159\/000239130","article-title":"Pharmacokinetic properties of the trypanocidal drug melarsoprol","volume":"39","author":"C Burri","year":"1993","journal-title":"Chemotherapy"},{"key":"ref49","first-page":"134","article-title":"Epidemiological studies on the animal reservoir of gambiense sleeping sickness. Part II. Parasitological and immunodiagnostic examination of the human population","volume":"32","author":"P Felgner","year":"1981","journal-title":"Tropenmed Parasitol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.actatropica.2006.09.003","article-title":"Comparison of the in vitro drug sensitivity of Trypanosoma brucei gambiense strains from West and Central Africa isolated in the periods 1960\u20131995 and 1999\u20132004","volume":"100","author":"ACL Likeufack","year":"2006","journal-title":"Acta Trop"},{"key":"ref51","first-page":"309","article-title":"Production of metacyclic forms by cyclical transmission of west African Trypanosoma (T.) brucei isolates from man and animals","volume":"45","author":"D Richner","year":"1988","journal-title":"Acta Trop"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1046\/j.1365-3156.2001.00775.x","article-title":"The phenomenon of treatment failures in Human African Trypanosomiasis","volume":"6","author":"R Brun","year":"2001","journal-title":"Trop Med Int Heal TM IH"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.trstmh.2006.11.008","article-title":"Isolation and propagation of Trypanosoma brucei gambiense from sleeping sickness patients in south Sudan","volume":"101","author":"NWN Maina","year":"2007","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1046\/j.1365-3156.1997.d01-122.x","article-title":"Susceptibility of Ugandan Trypanosoma brucei rhodesiense isolated from man and animal reservoirs to diminazene, isometamidium and melarsoprol","volume":"2","author":"E Matovu","year":"1997","journal-title":"Trop Med Int Heal TM IH"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"42","DOI":"10.2307\/3282933","article-title":"Effect of in vitro cultivation on the stability of resistance of Trypanosoma brucei brucei to diminazene, isometamidium, quinapyramine, and Mel B","volume":"75","author":"R Kaminsky","year":"1989","journal-title":"J Parasitol"}],"container-title":["PLoS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0002475","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T19:57:59Z","timestamp":1588967879000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0002475"}},"subtitle":[],"editor":[{"given":"Enock","family":"Matovu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,10,10]]},"references-count":55,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2013,10,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0002475","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,10]]}}}