{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:36:03Z","timestamp":1791941763886,"version":"4.3.4"},"reference-count":21,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T00:00:00Z","timestamp":1133395200000},"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":[[2005,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Metronidazole and related 5-nitroimidazoles are the only available drugs in the treatment of human urogenital trichomoniasis caused by the protozoan parasite\n                    <jats:italic>Trichomonas vaginalis<\/jats:italic>\n                    . The drugs are activated to cytotoxic anion radicals by their reduction within the hydrogenosomes. It has been established that electrons required for metronidazole activation are released from pyruvate by the activity of pyruvate:ferredoxin oxidoreductase and transferred to the drug by a low-redox-potential carrier, ferredoxin. Here we describe a novel pathway involved in the drug activation within the hydrogenosome. The source of electrons is malate, another major hydrogenosomal substrate, which is oxidatively decarboxylated to pyruvate and CO\n                    <jats:sub>2<\/jats:sub>\n                    by NAD-dependent malic enzyme. The electrons released during this reaction are transferred from NADH to ferredoxin by NADH dehydrogenase homologous to the catalytic module of mitochondrial complex I, which uses ferredoxin as electron acceptor. Trichomonads acquire high-level metronidazole resistance only after both pyruvate- and malate-dependent pathways of metronidazole activation are eliminated from the hydrogenosomes.\n                  <\/jats:p>","DOI":"10.1128\/aac.49.12.5033-5036.2005","type":"journal-article","created":{"date-parts":[[2005,11,22]],"date-time":"2005-11-22T16:57:58Z","timestamp":1132678678000},"page":"5033-5036","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":66,"title":["Alternative Pathway of Metronidazole Activation in\n                    <i>Trichomonas vaginalis<\/i>\n                    Hydrogenosomes"],"prefix":"10.1128","volume":"49","author":[{"given":"Ivan","family":"Hrdy\u0301","sequence":"first","affiliation":[{"name":"Department of Parasitology, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Cammack","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Research Division, King's College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Stopka","sequence":"additional","affiliation":[{"name":"Institute of Inorganic Chemistry, Czech Academy of Sciences, R\u030cez\u030c, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslav","family":"Kulda","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Tachezy","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0166-6851(84)90058-6","volume":"11","year":"1984","unstructured":"Cerkasovova, A., J. Cerkasov, and J. Kulda. 1984. Metabolic differences between metronidazole resistant and susceptible strains of Tritrichomonas foetus. Mol. Biochem. Parasitol.11:105-118.","journal-title":"Mol. Biochem. Parasitol."},{"key":"e_1_3_2_3_2","first-page":"2141","volume":"131","year":"1985","unstructured":"Chapman, A., R. Cammack, D. Linstead, and D. Lloyd. 1985. The generation of metronidazole radicals in hydrogenosomes isolated from Trichomonas vaginalis. J. Gen. Microbiol.131:2141-2144.","journal-title":"J. Gen. Microbiol."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.15.3.329-341.2002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(96)02777-6"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/31.2.201"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03149"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(98)00155-6"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.1993.tb04915.x"},{"key":"e_1_3_2_10_2","first-page":"394","volume":"58","year":"1982","unstructured":"Kulda, J., M. Vojtechovska, J. Tachezy, P. Demes, and E. Kunzova. 1982. Metronidazole resistance of Trichomonas vaginalis as a cause of treatment failure in trichomoniasis\u2014a case report. Br. J. Vener. Dis.58:394-399.","journal-title":"Br. J. Vener. Dis."},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1046\/j.1365-2958.2003.03791.x","volume":"51","year":"2004","unstructured":"Land, K. M., M. G. Gadillo-Correa, J. Tachezy, S. Vanacova, C. L. Hsieh, R. Sutak, and P. J. Johnson. 2004. Targeted gene replacement of a ferredoxin gene in Trichomonas vaginalis does not lead to metronidazole resistance. Mol. Microbiol.51:115-122.","journal-title":"Mol. 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Coombs. 1987. Comparative study of ferredoxin-linked and oxygen-metabolizing enzymes of trichomonads. Comp. Biochem. Physiol. B87:637-641.","journal-title":"Comp. Biochem. Physiol. 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