{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:04:08Z","timestamp":1791273848411,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"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":[[2013,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Giardiasis is one of the most common causes of diarrheal disease worldwide. Treatment is primarily with 5-nitro antimicrobials, particularly metronidazole. Resistance to metronidazole has been described, and treatment failures can occur in up to 20% of cases, making development of alternative antigiardials an important goal. To this end, we have screened a chemical library of 746 approved human drugs and 164 additional bioactive compounds for activity against\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Giardia lamblia<\/jats:named-content>\n                    . We identified 56 compounds that caused significant inhibition of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">G. lamblia<\/jats:named-content>\n                    growth and attachment. Of these, 15 were previously reported to have antigiardial activity, 20 were bioactive but not approved for human use, and 21 were drugs approved for human use for other indications. One notable compound of the last group was the antirheumatic drug auranofin. Further testing revealed that auranofin was active in the low (4 to 6)-micromolar range against a range of divergent\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">G. lamblia<\/jats:named-content>\n                    isolates representing both human-pathogenic assemblages A and B. Most importantly, auranofin was active against multiple metronidazole-resistant strains. Mechanistically, auranofin blocked the activity of giardial thioredoxin oxidoreductase, a critical enzyme involved in maintaining normal protein function and combating oxidative damage, suggesting that this inhibition contributes to the antigiardial activity. Furthermore, auranofin was efficacious\n                    <jats:italic>in vivo<\/jats:italic>\n                    , as it eradicated infection with different\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">G. lamblia<\/jats:named-content>\n                    isolates in different rodent models. These results indicate that the approved human drug auranofin could be developed as a novel agent in the armamentarium of antigiardial drugs, particularly against metronidazole-resistant strains.\n                  <\/jats:p>","DOI":"10.1128\/aac.01675-12","type":"journal-article","created":{"date-parts":[[2013,2,12]],"date-time":"2013-02-12T20:16:33Z","timestamp":1360700193000},"page":"2029-2035","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":138,"title":["A Reprofiled Drug, Auranofin, Is Effective against Metronidazole-Resistant Giardia lamblia"],"prefix":"10.1128","volume":"57","author":[{"given":"Noa","family":"Tejman-Yarden","sequence":"first","affiliation":[{"name":"Departments of Medicine, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Departments of Medicine, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Leitsch","sequence":"additional","affiliation":[{"name":"Department of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Santini","sequence":"additional","affiliation":[{"name":"Neurosciences, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjan","family":"Debnath","sequence":"additional","affiliation":[{"name":"The Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Gut","sequence":"additional","affiliation":[{"name":"The Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James H.","family":"McKerrow","sequence":"additional","affiliation":[{"name":"The Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon L.","family":"Reed","sequence":"additional","affiliation":[{"name":"Departments of Medicine, University of California, San Diego, La Jolla, California, USA"},{"name":"Pathology University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Eckmann","sequence":"additional","affiliation":[{"name":"Departments of Medicine, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2006.02.015"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-300220"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.1.114-128.2001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00384-11"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.8.12.1885"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.1.150-164.2001"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2.6.529"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00618-10"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mimet.2010.12.026"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2758"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0169-4758(88)90115-9"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(92)90095-T"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2010.03.004"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0001-706X(95)00100-S"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm900356n"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr192"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/20.4.519"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.020701"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-009-0466-z"},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1080\/15027732.1986.12461436","article-title":"Pharmacology of auranofin: overview and update","volume":"63","author":"Gottlieb NL","year":"1986","unstructured":"GottliebNL. 1986. 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