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T richomonas vaginalis flavin reductase 1 and its role in metronidazole resistance
Author(s) -
Leitsch David,
Janssen Brian D.,
Kolarich Daniel,
Johnson Patricia J.,
Duchêne Michael
Publication year - 2014
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12455
Subject(s) - flavin group , biology , reductase , plasmid , trichomonas vaginalis , metronidazole , microbiology and biotechnology , flavin adenine dinucleotide , biochemistry , gene , enzyme , antibiotics , cofactor
Summary The enzyme flavin reductase 1 ( FR 1) from T richomonas vaginalis , formerly known as NADPH oxidase, was isolated and identified. Flavin reductase is part of the antioxidative defence in T . vaginalis and indirectly reduces molecular oxygen to hydrogen peroxide via free flavins. Importantly, a reduced or absent flavin reductase activity has been reported in metronidazole‐resistant T . vaginalis , resulting in elevated intracellular oxygen levels and futile cycling of metronidazole. Interestingly, FR 1 has no close homologue in any other sequenced genome, but seven full‐length and three truncated isoforms exist in the T . vaginalis genome. However, out of these, only FR 1 has an affinity for flavins, i.e. FMN , FAD 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 FR 1‐ mRNA structure in any of the strains studied, FR 1 is not expressed in highly metronidazole‐resistant strains. Transfection of a metronidazole‐resistant clinical isolate ( B 7268), which does not express any detectable amounts of FR , with a plasmid bearing a functional FR 1 gene nearly completely restored metronidazole sensitivity. Our results indicate that FR 1 has a significant role in the emergence of metronidazole resistance in T . vaginalis .