{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T01:31:45Z","timestamp":1783474305139,"version":"3.55.0"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Benznidazole (Bz), the drug used for treatment of Chagas' disease (caused by the protozoan\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Trypanosoma cruzi<\/jats:named-content>\n            ), is activated by a parasitic NADH-dependent type I nitroreductase (NTR I). However, several studies have shown that other enzymes are involved. The aim of this study was to evaluate whether the aldo-keto reductase from\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. cruzi<\/jats:named-content>\n            (\n            <jats:italic>Tc<\/jats:italic>\n            AKR), a NADPH-dependent oxido-reductase previously described by our group, uses Bz as the substrate. We demonstrated that both recombinant and native\n            <jats:italic>Tc<\/jats:italic>\n            AKR enzymes reduce Bz by using NADPH, but not NADH, as a cofactor.\n            <jats:italic>Tc<\/jats:italic>\n            AKR-overexpressing epimastigotes showed higher NADPH-dependent Bz reductase activity and a 50% inhibitory concentration (IC\n            <jats:sub>50<\/jats:sub>\n            ) value for Bz 1.8-fold higher than that of the controls, suggesting that\n            <jats:italic>Tc<\/jats:italic>\n            AKR is involved in Bz detoxification instead of activation. To understand the role of\n            <jats:italic>Tc<\/jats:italic>\n            AKR in Bz metabolism, we studied\n            <jats:italic>Tc<\/jats:italic>\n            AKR expression and NADPH\/NADH-dependent Bz reductase activities in two\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. cruzi<\/jats:named-content>\n            strains with differential susceptibility to Bz: CL Brener and Nicaragua. Taking into account the results obtained with\n            <jats:italic>Tc<\/jats:italic>\n            AKR-overexpressing epimastigotes, we expected the more resistant strain, Nicaragua, to have higher\n            <jats:italic>Tc<\/jats:italic>\n            AKR levels than CL Brener. However, the results were the opposite. CL Brener showed 2-fold higher\n            <jats:italic>Tc<\/jats:italic>\n            AKR expression and 5.7-fold higher NADPH-Bz reduction than the Nicaragua strain. In addition, NADH-dependent Bz reductase activity, characteristic of NTR I, was also higher in CL Brener than in Nicaragua. We conclude that although\n            <jats:italic>Tc<\/jats:italic>\n            AKR uses Bz as the substrate,\n            <jats:italic>Tc<\/jats:italic>\n            AKR activity is not a determinant of Bz resistance in wild-type strains and may be overcome by other enzymes involved in Bz activation, such as NADPH- and NADH-dependent reductases.\n          <\/jats:p>","DOI":"10.1128\/aac.02185-15","type":"journal-article","created":{"date-parts":[[2016,2,9]],"date-time":"2016-02-09T04:33:28Z","timestamp":1454992408000},"page":"2664-2670","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Putative Role of the Aldo-Keto Reductase from Trypanosoma cruzi in Benznidazole Metabolism"],"prefix":"10.1128","volume":"60","author":[{"given":"Patricia Andrea","family":"Garavaglia","sequence":"first","affiliation":[{"name":"Instituto Nacional de Parasitolog\u00eda \u201cDr. Mario Fatala Chaben\u201d\u2014ANLIS \u201cDr. Carlos G. Malbr\u00e1n,\u201d Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Laverri\u00e8re","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biotecnol\u00f3gicas, Universidad Nacional de General San Mart\u00edn-CONICET, San Mart\u00edn, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn J. B.","family":"Cannata","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biotecnol\u00f3gicas, Universidad Nacional de General San Mart\u00edn-CONICET, San Mart\u00edn, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Andrea","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Parasitolog\u00eda \u201cDr. Mario Fatala Chaben\u201d\u2014ANLIS \u201cDr. Carlos G. Malbr\u00e1n,\u201d Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762002000500002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2009.11.003"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60061-X"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762009000900023"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.2174\/156802611796575894"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2010.11.010"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711014105"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05135-11"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2014.01.002"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(82)90383-6"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/6.2.223"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0742-8413(88)90036-9"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(02)01663-5"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.7.2701-2709.2005"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2008.04.011"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr700659m"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002844"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01941187"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2010.05.019"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1750431"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(85)90033-5"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2014.03.013"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-6-32"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2010.05.010"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020885"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01227-12"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(99)00264-6"},{"key":"e_1_3_2_29_2","first-page":"61","article-title":"Effects of buthionine sulfoximine nifurtimox and benznidazole upon trypanothione and metallothionein proteins in Trypanosoma cruzi","volume":"37","author":"Maya JD","year":"2004","unstructured":"Maya JD, Rodr\u00edguez A, Pino L, Pabon A, Ferreira J, Pavani M, Repetto Y, Morello A. 2004. Effects of buthionine sulfoximine nifurtimox and benznidazole upon trypanothione and metallothionein proteins in Trypanosoma cruzi. Biol Res 37:61\u201369.","journal-title":"Biol Res"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2005.12.001"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02185-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02185-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:45:31Z","timestamp":1645476331000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02185-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,5]]}},"alternative-id":["10.1128\/AAC.02185-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.02185-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5]]},"assertion":[{"value":"2015-09-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-04-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}