{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:36:07Z","timestamp":1791941767350,"version":"4.3.4"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,11,20]],"date-time":"2013-11-20T00:00:00Z","timestamp":1384905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2014,1]]},"abstract":"Summary<\/jats:title>\n \n The enzyme flavin reductase 1 (\n FR<\/jats:styled-content>\n 1) from\n \n T<\/jats:styled-content>\n richomonas vaginalis\n <\/jats:italic>\n , formerly known as\n NADPH<\/jats:styled-content>\n oxidase, was isolated and identified. Flavin reductase is part of the antioxidative defence in\n \n T<\/jats:styled-content>\n <\/jats:italic>\n .\n vaginalis<\/jats:italic>\n and indirectly reduces molecular oxygen to hydrogen peroxide via free flavins. Importantly, a reduced or absent flavin reductase activity has been reported in metronidazole\u2010resistant\n \n T<\/jats:styled-content>\n . vaginalis\n <\/jats:italic>\n , resulting in elevated intracellular oxygen levels and futile cycling of metronidazole. Interestingly,\n FR<\/jats:styled-content>\n 1 has no close homologue in any other sequenced genome, but seven full\u2010length and three truncated isoforms exist in the\n \n T<\/jats:styled-content>\n . vaginalis\n <\/jats:italic>\n genome. However, out of these, only\n FR<\/jats:styled-content>\n 1 has an affinity for flavins, i.e.\n FMN<\/jats:styled-content>\n ,\n FAD<\/jats:styled-content>\n and riboflavin, which is high enough to be of physiological relevance. Although there are no relevant changes in the gene sequence or any alterations of the predicted\n FR<\/jats:styled-content>\n 1\u2010\n mRNA<\/jats:styled-content>\n structure in any of the strains studied,\n FR<\/jats:styled-content>\n 1 is not expressed in highly metronidazole\u2010resistant strains. Transfection of a metronidazole\u2010resistant clinical isolate (\n B<\/jats:styled-content>\n 7268), which does not express any detectable amounts of\n FR<\/jats:styled-content>\n , with a plasmid bearing a functional\n FR<\/jats:styled-content>\n 1 gene nearly completely restored metronidazole sensitivity. Our results indicate that\n FR<\/jats:styled-content>\n 1 has a significant role in the emergence of metronidazole resistance in\n \n T<\/jats:styled-content>\n . vaginalis\n <\/jats:italic>\n .\n <\/jats:p>","DOI":"10.1111\/mmi.12455","type":"journal-article","created":{"date-parts":[[2013,11,7]],"date-time":"2013-11-07T00:22:36Z","timestamp":1383783756000},"page":"198-208","source":"Crossref","is-referenced-by-count":67,"title":["\n T<\/scp>\n richomonas vaginalis\n <\/i>\n flavin reductase 1 and its role in metronidazole resistance"],"prefix":"10.1111","volume":"91","author":[{"given":"David","family":"Leitsch","sequence":"first","affiliation":[{"name":"Institute of Specific Prophylaxis and Tropical Medicine Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics University of California Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Kolarich","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Colloids and Interfaces Department of Biomolecular Systems 14424 Potsdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia J.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics University of California Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Duch\u00eane","sequence":"additional","affiliation":[{"name":"Institute of Specific Prophylaxis and Tropical Medicine Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna 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