{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:16:58Z","timestamp":1790745418738,"version":"4.1.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"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":[[2011,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Infections with the diarrheagenic protozoan pathogen\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            are most commonly treated with metronidazole (Mz). Treatment failures with Mz occur in 10 to 20% of cases and Mz resistance develops in the laboratory, yet clinically, Mz-resistant (Mz\n            <jats:sup>r<\/jats:sup>\n            )\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            has rarely been isolated from patients. To understand why clinical Mz\n            <jats:sup>r<\/jats:sup>\n            isolates are rare, we questioned whether Mz resistance entails fitness costs to the parasite. Our studies employed several newly generated and established isogenic Mz\n            <jats:sup>r<\/jats:sup>\n            cell lines with stable, high-level resistance to Mz and significant cross-resistance to tinidazole, nitazoxanide, and furazolidone. Oral infection of suckling mice revealed that three of five Mz\n            <jats:sup>r<\/jats:sup>\n            cell lines could not establish infection, while two Mz\n            <jats:sup>r<\/jats:sup>\n            cell lines infected pups, albeit with reduced efficiencies. Failure to colonize resulted from a diminished capacity of the parasite to attach to the intestinal mucosa\n            <jats:italic>in vivo<\/jats:italic>\n            and to epithelial cells and plastic surfaces\n            <jats:italic>in vitro<\/jats:italic>\n            . The attachment defect was related to impaired glucose metabolism, since the noninfectious Mz\n            <jats:sup>r<\/jats:sup>\n            lines consumed less glucose, and glucose promoted ATP-independent parasite attachment in the parental lines. Thus, resistance of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Giardia<\/jats:named-content>\n            to Mz is accompanied by a glucose metabolism-related attachment defect that can interfere with colonization of the host. Because glucose-metabolizing pathways are important for activation of the prodrug Mz, it follows that a fitness trade-off exists between diminished Mz activation and reduced infectivity, which may explain the observed paucity of clinical Mz\n            <jats:sup>r<\/jats:sup>\n            isolates of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Giardia<\/jats:named-content>\n            . However, the data also caution that some forms of Mz resistance do not markedly interfere with\n            <jats:italic>in vivo<\/jats:italic>\n            infectivity.\n          <\/jats:p>","DOI":"10.1128\/aac.00384-11","type":"journal-article","created":{"date-parts":[[2011,8,9]],"date-time":"2011-08-09T06:30:16Z","timestamp":1312871416000},"page":"4643-4651","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":61,"title":["Impaired Parasite Attachment as Fitness Cost of Metronidazole Resistance in Giardia lamblia"],"prefix":"10.1128","volume":"55","author":[{"given":"Noa","family":"Tejman-Yarden","sequence":"first","affiliation":[{"name":"Departments of Medicine, University of California, San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Millman","sequence":"additional","affiliation":[{"name":"Departments of Medicine, University of California, San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tineke","family":"Lauwaet","sequence":"additional","affiliation":[{"name":"Pathology, University of California, San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara J.","family":"Davids","sequence":"additional","affiliation":[{"name":"Pathology, University of California, San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances D.","family":"Gillin","sequence":"additional","affiliation":[{"name":"Pathology, University of California, San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Dunn","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research, Herston, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline A.","family":"Upcroft","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research, Herston, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Departments of Medicine, University of California, San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Eckmann","sequence":"additional","affiliation":[{"name":"Departments of Medicine, University of California, San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2317"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2009.05.015"},{"key":"e_1_3_2_4_2","first-page":"783","article-title":"Giardia lamblia in peritoneal fluid","volume":"31","author":"Bloch T.","year":"1987","unstructured":"BlochT. 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