{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:17:29Z","timestamp":1790929049944,"version":"4.1.0"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"27","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,7,3]]},"abstract":"<jats:p>\n                    African trypanosomes cause sleeping sickness in humans, a disease that is typically fatal without chemotherapy. Unfortunately, drug resistance is common and melarsoprol-resistant trypanosomes often display cross-resistance to pentamidine. Although melarsoprol\/pentamidine cross-resistance (MPXR) has been an area of intense interest for several decades, our understanding of the underlying mechanisms remains incomplete. Recently, a locus encoding two closely related aquaglyceroporins, AQP2 and AQP3, was linked to MPXR in a high-throughput loss-of-function screen. Here, we show that AQP2 has an unconventional \u201cselectivity filter.\u201d\n                    <jats:italic>AQP2<\/jats:italic>\n                    -specific gene knockout generated MPXR trypanosomes but did not affect resistance to a lipophilic arsenical, whereas recombinant\n                    <jats:italic>AQP2<\/jats:italic>\n                    reversed MPXR in cells lacking native\n                    <jats:italic>AQP2<\/jats:italic>\n                    and\n                    <jats:italic>AQP3<\/jats:italic>\n                    .\n                    <jats:italic>AQP2<\/jats:italic>\n                    was also shown to be disrupted in a laboratory-selected MPXR strain. Both AQP2 and AQP3 gained access to the surface plasma membrane in insect life-cycle\u2013stage trypanosomes but, remarkably, AQP2 was specifically restricted to the flagellar pocket in the bloodstream stage. We conclude that the unconventional aquaglyceroporin, AQP2, renders cells sensitive to both melarsoprol and pentamidine and that loss of AQP2 function could explain cases of innate and acquired MPXR.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1202885109","type":"journal-article","created":{"date-parts":[[2012,6,18]],"date-time":"2012-06-18T23:15:14Z","timestamp":1340061314000},"page":"10996-11001","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":153,"title":["Aquaglyceroporin 2 controls susceptibility to melarsoprol and pentamidine in African trypanosomes"],"prefix":"10.1073","volume":"109","author":[{"given":"Nicola","family":"Baker","sequence":"first","affiliation":[{"name":"Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Glover","sequence":"additional","affiliation":[{"name":"Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane C.","family":"Munday","sequence":"additional","affiliation":[{"name":"College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Aguinaga Andr\u00e9s","sequence":"additional","affiliation":[{"name":"College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Barrett","sequence":"additional","affiliation":[{"name":"College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry P.","family":"de Koning","sequence":"additional","affiliation":[{"name":"College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Horn","sequence":"additional","affiliation":[{"name":"Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,6,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1111\/j.1469-0691.2011.03536.x","article-title":"Sleeping sickness","volume":"17","author":"Malvy D","year":"2011","unstructured":"D Malvy, F Chappuis, Sleeping sickness. 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Lancet 375, 148\u2013159 (2010).","journal-title":"Lancet"},{"key":"e_1_3_4_4_2","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 Trypanosoma brucei rhodesiense to D,L-\u03b1-difluoromethylornithine","volume":"41","author":"Iten M","year":"1997","unstructured":"M Iten, et al., Alterations in ornithine decarboxylase characteristics account for tolerance of Trypanosoma brucei rhodesiense to D,L-\u03b1-difluoromethylornithine. Antimicrob Agents Chemother 41, 1922\u20131925 (1997).","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_3_4_5_2","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":"Alsford S","year":"2012","unstructured":"S Alsford, et al., High-throughput decoding of antitrypanosomal drug efficacy and resistance. Nature 482, 232\u2013236 (2012).","journal-title":"Nature"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1073\/pnas.86.8.2607","article-title":"Trypanothione is the primary target for arsenical drugs against African trypanosomes","volume":"86","author":"Fairlamb AH","year":"1989","unstructured":"AH Fairlamb, GB Henderson, A Cerami, Trypanothione is the primary target for arsenical drugs against African trypanosomes. 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IUBMB Life 61, 112\u2013133 (2009).","journal-title":"IUBMB Life"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/nrm1469","article-title":"From structure to disease: The evolving tale of aquaporin biology","volume":"5","author":"King LS","year":"2004","unstructured":"LS King, D Kozono, P Agre, From structure to disease: The evolving tale of aquaporin biology. Nat Rev Mol Cell Biol 5, 687\u2013698 (2004).","journal-title":"Nat Rev Mol Cell Biol"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1042\/BC20040095","article-title":"Aquaporins from pathogenic protozoan parasites: structure, function and potential for chemotherapy","volume":"97","author":"Beitz E","year":"2005","unstructured":"E Beitz, Aquaporins from pathogenic protozoan parasites: structure, function and potential for chemotherapy. Biol Cell 97, 373\u2013383 (2005).","journal-title":"Biol Cell"},{"key":"e_1_3_4_24_2","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":"Uzcategui NL","year":"2004","unstructured":"NL Uzcategui, et al., Cloning, heterologous expression, and characterization of three aquaglyceroporins from Trypanosoma brucei. J Biol Chem 279, 42669\u201342676 (2004).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1111\/j.1365-2958.2006.05325.x","article-title":"Ammonia permeability of the aquaglyceroporins from Plasmodium falciparum, Toxoplasma gondii and Trypansoma brucei","volume":"61","author":"Zeuthen T","year":"2006","unstructured":"T Zeuthen, et al., Ammonia permeability of the aquaglyceroporins from Plasmodium falciparum, Toxoplasma gondii and Trypansoma brucei. Mol Microbiol 61, 1598\u20131608 (2006).","journal-title":"Mol Microbiol"},{"key":"e_1_3_4_26_2","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":"Bassarak B","year":"2011","unstructured":"B Bassarak, NL Uzc\u00e1tegui, C Sch\u00f6nfeld, M Duszenko, Functional characterization of three aquaglyceroporins from Trypanosoma brucei in osmoregulation and glycerol transport. Cell Physiol Biochem 27, 411\u2013420 (2011).","journal-title":"Cell Physiol Biochem"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1126\/science.1066115","article-title":"Water permeation across biological membranes: Mechanism and dynamics of aquaporin-1 and GlpF","volume":"294","author":"de Groot BL","year":"2001","unstructured":"BL de Groot, H Grubm\u00fcller, Water permeation across biological membranes: Mechanism and dynamics of aquaporin-1 and GlpF. Science 294, 2353\u20132357 (2001).","journal-title":"Science"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"17164","DOI":"10.1073\/pnas.1009864107","article-title":"Structural context shapes the aquaporin selectivity filter","volume":"107","author":"Savage DF","year":"2010","unstructured":"DF Savage, JD O\u2019Connell, LJ Miercke, J Finer-Moore, RM Stroud, Structural context shapes the aquaporin selectivity filter. Proc Natl Acad Sci USA 107, 17164\u201317169 (2010).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1038\/414872a","article-title":"Structural basis of water-specific transport through the AQP1 water channel","volume":"414","author":"Sui H","year":"2001","unstructured":"H Sui, BG Han, JK Lee, P Walian, BK Jap, Structural basis of water-specific transport through the AQP1 water channel. Nature 414, 872\u2013878 (2001).","journal-title":"Nature"},{"key":"e_1_3_4_30_2","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":"Gupta AB","year":"2012","unstructured":"AB Gupta, et al., MIPModDB: A central resource for the superfamily of major intrinsic proteins. Nucleic Acids Res 40, D362\u2013D369 (2012).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.mib.2007.09.014","article-title":"The cell biology of Trypanosoma brucei differentiation","volume":"10","author":"Fenn K","year":"2007","unstructured":"K Fenn, KR Matthews, The cell biology of Trypanosoma brucei differentiation. Curr Opin Microbiol 10, 539\u2013546 (2007).","journal-title":"Curr Opin Microbiol"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/nrmicro2221","article-title":"The trypanosome flagellar pocket","volume":"7","author":"Field MC","year":"2009","unstructured":"MC Field, M Carrington, The trypanosome flagellar pocket. Nat Rev Microbiol 7, 775\u2013786 (2009).","journal-title":"Nat Rev Microbiol"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"54887","DOI":"10.1074\/jbc.M409311200","article-title":"Cytoplasmic targeting signals in transmembrane invariant surface glycoproteins of trypanosomes","volume":"279","author":"Chung WL","year":"2004","unstructured":"WL Chung, M Carrington, MC Field, Cytoplasmic targeting signals in transmembrane invariant surface glycoproteins of trypanosomes. J Biol Chem 279, 54887\u201354895 (2004).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_34_2","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":"Teka IA","year":"2011","unstructured":"IA Teka, et al., The diamidine diminazene aceturate is a substrate for the high-affinity pentamidine transporter: Implications for the development of high resistance levels in trypanosomes. Mol Pharmacol 80, 110\u2013116 (2011).","journal-title":"Mol Pharmacol"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1111\/j.1550-7408.1980.tb05404.x","article-title":"Role of glycerol permeation in the bloodstream form of Trypanosoma brucei","volume":"27","author":"Gruenberg J","year":"1980","unstructured":"J Gruenberg, B Schwendimann, PR Sharma, J Deshusses, Role of glycerol permeation in the bloodstream form of Trypanosoma brucei. J Protozool 27, 484\u2013491 (1980).","journal-title":"J Protozool"},{"key":"e_1_3_4_36_2","first-page":"F685","article-title":"Functional and molecular characterization of the human neutral solute channel aquaporin-9","volume":"277","author":"Tsukaguchi H","year":"1999","unstructured":"H Tsukaguchi, S Weremowicz, CC Morton, MA Hediger, Functional and molecular characterization of the human neutral solute channel aquaporin-9. Am J Physiol 277, F685\u2013F696 (1999).","journal-title":"Am J Physiol"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1111\/j.1365-2958.2007.05845.x","article-title":"Biochemical characterization of Leishmania major aquaglyceroporin LmAQP1: Possible role in volume regulation and osmotaxis","volume":"65","author":"Figarella K","year":"2007","unstructured":"K Figarella, et al., Biochemical characterization of Leishmania major aquaglyceroporin LmAQP1: Possible role in volume regulation and osmotaxis. Mol Microbiol 65, 1006\u20131017 (2007).","journal-title":"Mol Microbiol"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/S0140-6736(05)66793-1","article-title":"Detection of arsenical drug resistance in Trypanosoma brucei with a simple fluorescence test","volume":"366","author":"Stewart ML","year":"2005","unstructured":"ML Stewart, et al., Detection of arsenical drug resistance in Trypanosoma brucei with a simple fluorescence test. Lancet 366, 486\u2013487 (2005).","journal-title":"Lancet"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1073\/pnas.0507225103","article-title":"Point mutations in the aromatic\/arginine region in aquaporin 1 allow passage of urea, glycerol, ammonia, and protons","volume":"103","author":"Beitz E","year":"2006","unstructured":"E Beitz, B Wu, LM Holm, JE Schultz, T Zeuthen, Point mutations in the aromatic\/arginine region in aquaporin 1 allow passage of urea, glycerol, ammonia, and protons. Proc Natl Acad Sci USA 103, 269\u2013274 (2006).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.jmb.2011.01.036","article-title":"Enhancement of proton conductance by mutations of the selectivity filter of aquaporin-1","volume":"407","author":"Li H","year":"2011","unstructured":"H Li, et al., Enhancement of proton conductance by mutations of the selectivity filter of aquaporin-1. 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Eur J Biochem 160, 175\u2013182 (1986).","journal-title":"Eur J Biochem"},{"key":"e_1_3_4_48_2","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":"Baker N","year":"2011","unstructured":"N Baker, S Alsford, D Horn, Genome-wide RNAi screens in African trypanosomes identify the nifurtimox activator NTR and the eflornithine transporter AAT6. 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Acta Trop 68, 139\u2013147 (1997).","journal-title":"Acta Trop"},{"key":"e_1_3_4_50_2","doi-asserted-by":"crossref","first-page":"e1000468","DOI":"10.1371\/journal.ppat.1000468","article-title":"The glycosylphosphatidylinositol-PLC in Trypanosoma brucei forms a linear array on the exterior of the flagellar membrane before and after activation","volume":"5","author":"Hanrahan O","year":"2009","unstructured":"O Hanrahan, et al., The glycosylphosphatidylinositol-PLC in Trypanosoma brucei forms a linear array on the exterior of the flagellar membrane before and after activation. 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