{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T06:40:13Z","timestamp":1775198413711,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1006307","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T00:00:00Z","timestamp":1491868800000}}],"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2017,3,30]],"date-time":"2017-03-30T00:00:00Z","timestamp":1490832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["100320\/Z\/12\/Z"],"award-info":[{"award-number":["100320\/Z\/12\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K000500\/1"],"award-info":[{"award-number":["MR\/K000500\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_156264"],"award-info":[{"award-number":["310030_156264"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1006307","type":"journal-article","created":{"date-parts":[[2017,3,30]],"date-time":"2017-03-30T19:27:53Z","timestamp":1490902073000},"page":"e1006307","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":40,"title":["Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity"],"prefix":"10.1371","volume":"13","author":[{"given":"Laura","family":"Jeacock","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Baker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Wiedemar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3122-1941","authenticated-orcid":true,"given":"Pascal","family":"M\u00e4ser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5173-9284","authenticated-orcid":true,"given":"David","family":"Horn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2017,3,30]]},"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":"56","DOI":"10.1016\/S0140-6736(09)61117-X","article-title":"Nifurtimox-eflornithine combination therapy for second-stage African <italic>Trypanosoma brucei gambiense<\/italic> trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial","volume":"374","author":"G Priotto","year":"2009","journal-title":"Lancet"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1128\/AAC.41.9.1922","article-title":"Alterations in ornithine decarboxylase characteristics account for tolerance of <italic>Trypanosoma brucei rhodesiense<\/italic> to D,L-\u03b1-difluoromethylornithine","volume":"41","author":"M Iten","year":"1997","journal-title":"Antimicrob Agents Chemother"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1365-3156.2005.01545.x","article-title":"Drug-resistance of <italic>Trypanosoma b<\/italic>. <italic>rhodesiense<\/italic> isolates from Tanzania","volume":"11","author":"SN Kibona","year":"2006","journal-title":"Trop Med Int Health"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"966","DOI":"10.3201\/eid1406.071266","article-title":"High failure rates of melarsoprol for sleeping sickness, Democratic Republic of Congo","volume":"14","author":"J Robays","year":"2008","journal-title":"Emerg Infect Dis"},{"key":"ref6","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":"ref7","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":"ref8","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1126\/science.285.5425.242","article-title":"A nucleoside transporter from <italic>Trypanosoma brucei<\/italic> involved in drug resistance","volume":"285","author":"P Maser","year":"1999","journal-title":"Science"},{"key":"ref9","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":"ref10","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1093\/jac\/dkt442","article-title":"<italic>Trypanosoma brucei<\/italic> aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs","volume":"69","author":"JC Munday","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1365-2125.1995.tb04451.x","article-title":"Pharmacokinetics and adverse reactions after a single dose of pentamidine in patients with <italic>Trypanosoma gambiense<\/italic> sleeping sickness","volume":"39","author":"U Bronner","year":"1995","journal-title":"British Journal of Clinical Pharmacology"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"e2475","DOI":"10.1371\/journal.pntd.0002475","article-title":"Aquaporin 2 mutations in <italic>Trypanosoma brucei gambiense<\/italic> field isolates correlate with decreased susceptibility to pentamidine and melarsoprol","volume":"7","author":"FE Graf","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e3212","DOI":"10.1371\/journal.pntd.0003212","article-title":"Melarsoprol sensitivity profile of <italic>Trypanosoma brucei gambiense<\/italic> isolates from cured and relapsed sleeping sickness patients from the Democratic Republic of the Congo","volume":"8","author":"P Pyana Pati","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ijpddr.2015.04.002","article-title":"Chimerization at the <italic>AQP2-AQP3<\/italic> locus is the genetic basis of melarsoprol-pentamidine cross-resistance in clinical <italic>Trypanosoma brucei gambiense<\/italic> isolates","volume":"5","author":"FE Graf","year":"2015","journal-title":"Int J Parasitol Drugs Drug Resist"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"31010","DOI":"10.1074\/jbc.M403959200","article-title":"Drug uptake and modulation of drug resistance in <italic>Leishmania<\/italic> by an aquaglyceroporin","volume":"279","author":"B Gourbal","year":"2004","journal-title":"J Biol Chem"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1159\/000327968","article-title":"Functional characterization of three aquaglyceroporins from <italic>Trypanosoma brucei<\/italic> in osmoregulation and glycerol transport","volume":"27","author":"B Bassarak","year":"2011","journal-title":"Cell Physiol Biochem"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.pt.2016.10.009","article-title":"TrypTag.org: A Trypanosome Genome-wide Protein Localisation Resource","volume":"33","author":"S Dean","year":"2017","journal-title":"Trends Parasitol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1111\/j.1365-2958.2006.05325.x","article-title":"Ammonia permeability of the aquaglyceroporins from <italic>Plasmodium falciparum<\/italic>, <italic>Toxoplasma gondii<\/italic> and <italic>Trypansoma brucei<\/italic>","volume":"61","author":"T Zeuthen","year":"2006","journal-title":"Mol Microbiol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.bbamem.2017.01.011","article-title":"Aquaglyceroporins Are the Entry Pathway of Boric Acid in <italic>Trypanosoma brucei<\/italic>","volume":"1859","author":"S Marsiccobetre","year":"2017","journal-title":"Biochim Biophys Acta"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"42669","DOI":"10.1074\/jbc.M404518200","article-title":"Cloning, heterologous expression, and characterization of three aquaglyceroporins from <italic>Trypanosoma brucei<\/italic>","volume":"279","author":"NL Uzcategui","year":"2004","journal-title":"J Biol Chem"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1159\/000354490","article-title":"<italic>Trypanosoma brucei<\/italic> aquaglyceroporins facilitate the uptake of arsenite and antimonite in a pH dependent way","volume":"32","author":"NL Uzcategui","year":"2013","journal-title":"Cell Physiol Biochem"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"e1005436","DOI":"10.1371\/journal.ppat.1005436","article-title":"Pentamidine Is not a permeant but a nanomolar inhibitor of the <italic>Trypanosoma brucei<\/italic> aquaglyceroporin-2","volume":"12","author":"J Song","year":"2016","journal-title":"PLoS Pathog"},{"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":"76","DOI":"10.1016\/j.molbiopara.2008.05.006","article-title":"Single-locus targeting constructs for reliable regulated RNAi and transgene expression in <italic>Trypanosoma brucei<\/italic>","volume":"161","author":"S Alsford","year":"2008","journal-title":"Mol Biochem Parasitol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"17718","DOI":"10.1073\/pnas.0806664105","article-title":"Compartmentation prevents a lethal turbo-explosion of glycolysis in trypanosomes","volume":"105","author":"JR Haanstra","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.pt.2006.08.007","article-title":"Trypanosome alternative oxidase: from molecule to function","volume":"22","author":"M Chaudhuri","year":"2006","journal-title":"Trends Parasitol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1126\/science.986688","article-title":"Trypanosomiasis: an approach to chemotherapy by the inhibition of carbohydrate catabolism","volume":"194","author":"AB Clarkson Jr.","year":"1976","journal-title":"Science"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0166-6851(86)90079-4","article-title":"Esters of 3,4-dihydroxybenzoic acid, highly effective inhibitors of the sn-glycerol-3-phosphate oxidase of <italic>Trypanosoma brucei<\/italic> brucei","volume":"21","author":"RW Grady","year":"1986","journal-title":"Mol Biochem Parasitol"},{"key":"ref29","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":"Tropenmedizin und Parasitologie"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0166-6851(01)00332-2","article-title":"Genetic variants of the <italic>TbAT1<\/italic> adenosine transporter from African trypanosomes in relapse infections following melarsoprol therapy","volume":"117","author":"E Matovu","year":"2001","journal-title":"Mol Biochem Parasitol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.trstmh.2006.11.008","article-title":"Isolation and propagation of <italic>Trypanosoma brucei gambiense<\/italic> from sleeping sickness patients in south Sudan","volume":"101","author":"NW Maina","year":"2007","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.parint.2005.09.003","article-title":"Chemotherapeutic efficacy of ascofuranone in <italic>Trypanosoma vivax<\/italic>-infected mice without glycerol","volume":"55","author":"Y Yabu","year":"2006","journal-title":"Parasitol Int"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1073\/pnas.0610843104","article-title":"Aquaglyceroporin PbAQP during intraerythrocytic development of the malaria parasite <italic>Plasmodium berghei<\/italic>","volume":"104","author":"D Promeneur","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.1073\/pnas.1117313109","article-title":"Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species","volume":"109","author":"AP Jackson","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1111\/j.1365-2958.2007.05845.x","article-title":"Biochemical characterization of <italic>Leishmania major<\/italic> aquaglyceroporin LmAQP1: possible role in volume regulation and osmotaxis","volume":"65","author":"K Figarella","year":"2007","journal-title":"Mol Microbiol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"38673","DOI":"10.1074\/jbc.M406304200","article-title":"A functional aquaporin co-localizes with the vacuolar proton pyrophosphatase to acidocalcisomes and the contractile vacuole complex of <italic>Trypanosoma cruzi<\/italic>","volume":"279","author":"A Montalvetti","year":"2004","journal-title":"J Biol Chem"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.molbiopara.2015.07.003","article-title":"Generation of an aquaglyceroporin AQP1 null mutant in <italic>Leishmania major<\/italic>","volume":"201","author":"M Plourde","year":"2015","journal-title":"Mol Biochem Parasitol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1042\/bj3190691","article-title":"An amino acid channel activated by hypotonically induced swelling of <italic>Leishmania major<\/italic> promastigotes","volume":"319","author":"LL Vieira","year":"1996","journal-title":"Biochem J"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s002329900138","article-title":"Volume-regulatory amino acid release from the protozoan parasite <italic>Crithidia luciliae<\/italic>","volume":"154","author":"JD Bursell","year":"1996","journal-title":"J Membrane Biol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1550-7408.2005.00030.x","article-title":"<italic>Leishmania donovani<\/italic> amastigotes mobilize organic and inorganic osmolytes during regulatory volume decrease","volume":"52","author":"A Lefurgey","year":"2005","journal-title":"The J Euk Microbiol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1074\/jbc.272.6.3207","article-title":"Glycolysis in bloodstream form <italic>Trypanosoma brucei<\/italic> can be understood in terms of the kinetics of the glycolytic enzymes","volume":"272","author":"BM Bakker","year":"1997","journal-title":"J Biol Chem"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/S0925-4439(02)00086-8","article-title":"Trypanosome alternative oxidase as a target of chemotherapy","volume":"1587","author":"C Nihei","year":"2002","journal-title":"Biochim Biophys Acta"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1128\/AAC.37.5.1082","article-title":"<italic>N<\/italic>-n-alkyl-3,4-dihydroxybenzamides as inhibitors of the trypanosome alternative oxidase: activity <italic>in vitro<\/italic> and <italic>in vivo<\/italic>","volume":"37","author":"RW Grady","year":"1993","journal-title":"Antimicrob Agents Chemother"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S0031182016002109","article-title":"The trypanosome alternative oxidase: a potential drug target?","author":"SK Menzies","year":"2016","journal-title":"Parasitology"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0035-9203(78)90065-2","article-title":"Effective treatment of <italic>Trypanosoma vivax<\/italic> infections with salicylhydroxamic acid (SHAM)","volume":"72","author":"DA Evans","year":"1978","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"4580","DOI":"10.1073\/pnas.1218386110","article-title":"Structure of the trypanosome cyanide-insensitive alternative oxidase","volume":"110","author":"T Shiba","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.pt.2012.05.003","article-title":"An alternative form of melarsoprol in sleeping sickness","volume":"28","author":"PG Kennedy","year":"2012","journal-title":"Trends Parasitol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.molbiopara.2005.08.009","article-title":"Tagging a <italic>T<\/italic>. <italic>brucei RRNA<\/italic> locus improves stable transfection efficiency and circumvents inducible expression position effects","volume":"144","author":"S Alsford","year":"2005","journal-title":"Mol Biochem Parasitol"},{"key":"ref49","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 (<italic>T<\/italic>. <italic>b<\/italic>. <italic>rhodesiense<\/italic> and <italic>T<\/italic>. <italic>b<\/italic>. <italic>gambiense<\/italic>) <italic>in vitro<\/italic>","volume":"68","author":"B Raz","year":"1997","journal-title":"Acta Trop"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0014-4894(86)90033-0","article-title":"<italic>Trypanosoma brucei<\/italic>: <italic>cis<\/italic>-aconitate and temperature reduction as triggers of synchronous transformation of bloodstream to procyclic trypomastigotes <italic>in vitro<\/italic>","volume":"62","author":"J Czichos","year":"1986","journal-title":"Exp Parasitol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1101\/gr.115089.110","article-title":"High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome","volume":"21","author":"S Alsford","year":"2011","journal-title":"Genome Res"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1046\/j.1432-1327.1998.2560245.x","article-title":"Characterization of glycerol uptake in bloodstream and procyclic forms of <italic>Trypanosoma brucei<\/italic>","volume":"256","author":"U Wille","year":"1998","journal-title":"Eur J Biochem"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1006307","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T00:00:00Z","timestamp":1491868800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1006307","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T07:49:22Z","timestamp":1568965762000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1006307"}},"subtitle":[],"editor":[{"given":"Scott M","family":"Landfear","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2017,3,30]]},"references-count":52,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,3,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1006307","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1006307","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,30]]}}}