{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T23:07:49Z","timestamp":1782688069964,"version":"3.54.5"},"reference-count":114,"publisher":"Cambridge University Press (CUP)","issue":"12","license":[{"start":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T00:00:00Z","timestamp":1364947200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>The trypanosomes cause two neglected tropical diseases, Chagas disease in the Americas and African trypanosomiasis in sub-Saharan Africa. Over recent years a raft of molecular tools have been developed enabling the genetic dissection of many aspects of trypanosome biology, including the mechanisms underlying resistance to some of the current clinical and veterinary drugs. This has led to the identification and characterization of key resistance determinants, including transporters for the anti-<jats:italic>Trypanosoma brucei<\/jats:italic>drugs, melarsoprol, pentamidine and eflornithine, and the activator of nifurtimox-benznidazole, the anti-<jats:italic>Trypanosoma cruzi<\/jats:italic>drugs. More recently, advances in sequencing technology, combined with the development of RNA interference libraries in the clinically relevant bloodstream form of<jats:italic>T. brucei<\/jats:italic>have led to an exponential increase in the number of proteins known to interact either directly or indirectly with the anti-trypanosomal drugs. In this review, we discuss these findings and the technological developments that are set to further revolutionise our understanding of drug-trypanosome interactions. The new knowledge gained should inform the development of novel interventions against the devastating diseases caused by these parasites.<\/jats:p>","DOI":"10.1017\/s003118201300022x","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T17:23:07Z","timestamp":1365009787000},"page":"1478-1491","source":"Crossref","is-referenced-by-count":50,"title":["Genetic dissection of drug resistance in trypanosomes"],"prefix":"10.1017","volume":"140","author":[{"given":"SAM","family":"ALSFORD","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JOHN M.","family":"KELLY","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NICOLA","family":"BAKER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DAVID","family":"HORN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2013,4,3]]},"reference":[{"key":"S003118201300022X_ref27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001454"},{"key":"S003118201300022X_ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2005.10.016"},{"key":"S003118201300022X_ref25","doi-asserted-by":"publisher","DOI":"10.1191\/0960327106het653oa"},{"key":"S003118201300022X_ref24","doi-asserted-by":"publisher","DOI":"10.1038\/361173a0"},{"key":"S003118201300022X_ref22","doi-asserted-by":"publisher","DOI":"10.1038\/nm1744"},{"key":"S003118201300022X_ref14","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(95)00120-P"},{"key":"S003118201300022X_ref12","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-4758(99)01414-3"},{"key":"S003118201300022X_ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2010.11.010"},{"key":"S003118201300022X_ref7","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(83)90022-1"},{"key":"S003118201300022X_ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2004.11.001"},{"key":"S003118201300022X_ref2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10771"},{"key":"S003118201300022X_ref29","doi-asserted-by":"publisher","DOI":"10.1124\/mol.59.3.586"},{"key":"S003118201300022X_ref20","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60829-1"},{"key":"S003118201300022X_ref16","doi-asserted-by":"publisher","DOI":"10.1086\/605091"},{"key":"S003118201300022X_ref54","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(94)90114-7"},{"key":"S003118201300022X_ref67","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(01)00332-2"},{"key":"S003118201300022X_ref108","unstructured":"WHO (2009). Statement \u2013 Chagas disease in Europe. World Health Organisation, Geneva, Switzerland. http:\/\/www.who.int\/neglected_diseases\/integrated_media_chagas_statement\/en\/index.html."},{"key":"S003118201300022X_ref10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1202885109"},{"key":"S003118201300022X_ref13","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.11.88"},{"key":"S003118201300022X_ref35","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309320200"},{"key":"S003118201300022X_ref97","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.8.3932"},{"key":"S003118201300022X_ref42","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.4.1521-1528.2005"},{"key":"S003118201300022X_ref45","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5319.1716"},{"key":"S003118201300022X_ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2011.10.003"},{"key":"S003118201300022X_ref19","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.031351"},{"key":"S003118201300022X_ref8","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(93)90524-Z"},{"key":"S003118201300022X_ref86","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02831.x"},{"key":"S003118201300022X_ref23","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":"Carter","year":"1995","journal-title":"Journal of Biological Chemistry"},{"key":"S003118201300022X_ref104","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(98)00324-4"},{"key":"S003118201300022X_ref96","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2003.08.008"},{"key":"S003118201300022X_ref101","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762009000900041"},{"key":"S003118201300022X_ref21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2535442100"},{"key":"S003118201300022X_ref26","doi-asserted-by":"publisher","DOI":"10.1586\/erv.09.45"},{"key":"S003118201300022X_ref66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000868"},{"key":"S003118201300022X_ref57","doi-asserted-by":"publisher","DOI":"10.1128\/EC.05114-11"},{"key":"S003118201300022X_ref40","doi-asserted-by":"publisher","DOI":"10.2147\/RRTM.S34399"},{"key":"S003118201300022X_ref109","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399409001252"},{"key":"S003118201300022X_ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2008.05.006"},{"key":"S003118201300022X_ref30","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2008.04.006"},{"key":"S003118201300022X_ref32","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2007.02.004"},{"key":"S003118201300022X_ref11","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/lds031"},{"key":"S003118201300022X_ref52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001151"},{"key":"S003118201300022X_ref17","doi-asserted-by":"publisher","DOI":"10.1186\/1752-1505-1-6"},{"key":"S003118201300022X_ref62","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102351200"},{"key":"S003118201300022X_ref106","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-398457-9.00004-4"},{"key":"S003118201300022X_ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2005.08.009"},{"key":"S003118201300022X_ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2010.10.015"},{"key":"S003118201300022X_ref91","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-1-3"},{"key":"S003118201300022X_ref88","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182012000169"},{"key":"S003118201300022X_ref110","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711014105"},{"key":"S003118201300022X_ref37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.8.2607"},{"key":"S003118201300022X_ref38","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(87)90020-4"},{"key":"S003118201300022X_ref39","doi-asserted-by":"publisher","DOI":"10.1038\/35888"},{"key":"S003118201300022X_ref80","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-308X(08)60410-8"},{"key":"S003118201300022X_ref41","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1949.s1-29.173"},{"key":"S003118201300022X_ref43","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4922(00)01827-4"},{"key":"S003118201300022X_ref44","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2009.03.010"},{"key":"S003118201300022X_ref46","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.230847"},{"key":"S003118201300022X_ref47","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05135-11"},{"key":"S003118201300022X_ref49","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2010.08.009"},{"key":"S003118201300022X_ref50","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-alpha-difluoromethylornithine","volume":"41","author":"Iten","year":"1997","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"S003118201300022X_ref51","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112680"},{"key":"S003118201300022X_ref34","doi-asserted-by":"publisher","DOI":"10.1016\/0009-2797(90)90106-W"},{"key":"S003118201300022X_ref53","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001691"},{"key":"S003118201300022X_ref56","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385863-4.00001-0"},{"key":"S003118201300022X_ref58","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(00)00300-5"},{"key":"S003118201300022X_ref59","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e32834a667f"},{"key":"S003118201300022X_ref61","doi-asserted-by":"publisher","DOI":"10.1126\/science.2177225"},{"key":"S003118201300022X_ref63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001161"},{"key":"S003118201300022X_ref64","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2008.04.001"},{"key":"S003118201300022X_ref71","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis331"},{"key":"S003118201300022X_ref94","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00141-06"},{"key":"S003118201300022X_ref68","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.5.1003-1008.2003"},{"key":"S003118201300022X_ref69","first-page":"2184","article-title":"Breakage of bacterial DNA by nitrofuran derivatives","volume":"31","author":"McCalla","year":"1971","journal-title":"Cancer Research"},{"key":"S003118201300022X_ref70","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762009000900034"},{"key":"S003118201300022X_ref72","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762009000900005"},{"key":"S003118201300022X_ref100","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001734"},{"key":"S003118201300022X_ref99","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385863-4.00011-3"},{"key":"S003118201300022X_ref73","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf474"},{"key":"S003118201300022X_ref75","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001246"},{"key":"S003118201300022X_ref76","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.25.14687"},{"key":"S003118201300022X_ref113","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003326"},{"key":"S003118201300022X_ref77","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3156.2005.01470.x"},{"key":"S003118201300022X_ref78","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2008.09.011"},{"key":"S003118201300022X_ref31","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.5.1515-1519.2004"},{"key":"S003118201300022X_ref102","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2009.10.023"},{"key":"S003118201300022X_ref79","doi-asserted-by":"publisher","DOI":"10.1021\/jm000159m"},{"key":"S003118201300022X_ref81","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(87)90064-8"},{"key":"S003118201300022X_ref82","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61117-X"},{"key":"S003118201300022X_ref83","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001541"},{"key":"S003118201300022X_ref87","doi-asserted-by":"publisher","DOI":"10.3201\/eid1712.110921"},{"key":"S003118201300022X_ref89","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00332-10"},{"key":"S003118201300022X_ref92","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00200-09"},{"key":"S003118201300022X_ref93","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015988401601"},{"key":"S003118201300022X_ref95","doi-asserted-by":"publisher","DOI":"10.1021\/jm900030h"},{"key":"S003118201300022X_ref98","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-6-32"},{"key":"S003118201300022X_ref103","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001204"},{"key":"S003118201300022X_ref105","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008405200"},{"key":"S003118201300022X_ref107","doi-asserted-by":"crossref","first-page":"5529","DOI":"10.1128\/JB.180.21.5529-5539.1998","article-title":"Oxygen-insensitive nitroreductases: analysis of the roles of nfsA and nfsB in development of resistance to 5-nitrofuran derivatives in Escherichia coli","volume":"180","author":"Whiteway","year":"1998","journal-title":"Journal of Bacteriology"},{"key":"S003118201300022X_ref111","doi-asserted-by":"publisher","DOI":"10.1126\/science.7761835"},{"key":"S003118201300022X_ref112","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(99)00002-X"},{"key":"S003118201300022X_ref48","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-5-45"},{"key":"S003118201300022X_ref114","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601956"},{"key":"S003118201300022X_ref33","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(09)70088-X"},{"key":"S003118201300022X_ref65","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":"Maser","year":"1999","journal-title":"Science"},{"key":"S003118201300022X_ref74","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2012.04.022"},{"key":"S003118201300022X_ref55","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/20.15.3963"},{"key":"S003118201300022X_ref90","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(95)02543-X"},{"key":"S003118201300022X_ref18","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112642"},{"key":"S003118201300022X_ref36","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112631"},{"key":"S003118201300022X_ref85","doi-asserted-by":"publisher","DOI":"10.1016\/0001-706X(96)00131-3"},{"key":"S003118201300022X_ref6","doi-asserted-by":"publisher","DOI":"10.1101\/gr.115089.110"},{"key":"S003118201300022X_ref84","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2010.09.002"},{"key":"S003118201300022X_ref60","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403479200"}],"container-title":["Parasitology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S003118201300022X","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T19:55:20Z","timestamp":1595620520000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S003118201300022X\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,3]]},"references-count":114,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2013,10]]}},"alternative-id":["S003118201300022X"],"URL":"https:\/\/doi.org\/10.1017\/s003118201300022x","relation":{},"ISSN":["0031-1820","1469-8161"],"issn-type":[{"value":"0031-1820","type":"print"},{"value":"1469-8161","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,3]]}}}