{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:36:00Z","timestamp":1791941760796,"version":"4.3.4"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2009,2,1]],"date-time":"2009-02-01T00:00:00Z","timestamp":1233446400000},"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":[[2009,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Infections with\n            <jats:italic>Giardia lamblia<\/jats:italic>\n            ,\n            <jats:italic>Entamoeba histolytica<\/jats:italic>\n            , and\n            <jats:italic>Trichomonas vaginalis<\/jats:italic>\n            , which cause diarrhea, dysentery, and vaginitis, respectively, are each treated with metronidazole. Here we show that\n            <jats:italic>Giardia<\/jats:italic>\n            ,\n            <jats:italic>Entamoeba<\/jats:italic>\n            , and\n            <jats:italic>Trichomonas<\/jats:italic>\n            have oxygen-insensitive nitroreductase (\n            <jats:italic>ntr<\/jats:italic>\n            ) genes which are homologous to those genes that have nonsense mutations in metronidazole-resistant\n            <jats:italic>Helicobacter pylori<\/jats:italic>\n            isolates.\n            <jats:italic>Entamoeba<\/jats:italic>\n            and\n            <jats:italic>Trichomonas<\/jats:italic>\n            also have\n            <jats:italic>nim<\/jats:italic>\n            genes which are homologous to those genes expressed in metronidazole-resistant\n            <jats:italic>Bacteroides fragilis<\/jats:italic>\n            isolates. Recombinant\n            <jats:italic>Giardia<\/jats:italic>\n            ,\n            <jats:italic>Entamoeba<\/jats:italic>\n            , and\n            <jats:italic>Trichomonas<\/jats:italic>\n            nitroreductases used NADH rather than the NADPH used by\n            <jats:italic>Helicobacter<\/jats:italic>\n            , and two recombinant\n            <jats:italic>Entamoeba<\/jats:italic>\n            nitroreductases increased the metronidazole sensitivity of transformed\n            <jats:italic>Escherichia coli<\/jats:italic>\n            strains. Conversely, the recombinant nitroimidazole reductases (NIMs) of\n            <jats:italic>Entamoeba<\/jats:italic>\n            and\n            <jats:italic>Trichmonas<\/jats:italic>\n            conferred very strong metronidazole resistance to transformed bacteria. The Eh\n            <jats:italic>ntr1<\/jats:italic>\n            gene of the genome project HM-1:IMSS strain of\n            <jats:italic>Entamoeba histolytica<\/jats:italic>\n            had a nonsense mutation, and the same nonsense mutation was present in 3 of 22 clinical isolates of\n            <jats:italic>Entamoeba<\/jats:italic>\n            . While\n            <jats:italic>ntr<\/jats:italic>\n            and\n            <jats:italic>nim<\/jats:italic>\n            mRNAs were variably expressed by cultured\n            <jats:italic>Entamoeba<\/jats:italic>\n            and\n            <jats:italic>Trichomonas<\/jats:italic>\n            isolates, there was no relationship to metronidazole sensitivity. We conclude that microaerophilic protists have bacterium-like enzymes capable of activating metronidazole (nitroreductases) and inactivating metronidazole (NIMs). While\n            <jats:italic>Entamoeba<\/jats:italic>\n            and\n            <jats:italic>Trichomonas<\/jats:italic>\n            displayed some of the changes (nonsense mutations and gene overexpression) associated with metronidazole resistance in bacteria, these changes did not confer metronidazole resistance to the microaerophilic protists examined here.\n          <\/jats:p>","DOI":"10.1128\/aac.00909-08","type":"journal-article","created":{"date-parts":[[2008,11,18]],"date-time":"2008-11-18T02:26:03Z","timestamp":1226975163000},"page":"458-464","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":83,"title":["<i>Giardia<\/i>\n            ,\n            <i>Entamoeba<\/i>\n            , and\n            <i>Trichomonas<\/i>\n            Enzymes Activate Metronidazole (Nitroreductases) and Inactivate Metronidazole (Nitroimidazole Reductases)"],"prefix":"10.1128","volume":"53","author":[{"given":"Dibyarupa","family":"Pal","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Indian Institute of Technology, Kharagpur, West Bengal 721302, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulagna","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jike","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudip K.","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Indian Institute of Technology, Kharagpur, West Bengal 721302, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Samuelson","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.3.447-475.2001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10156-004-0370-Y","volume":"11","year":"2005","unstructured":"Aldana, L. 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