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  • Trichomonas vaginalis flavin reductase 1 and its role in metronidazole resistance

    Author(s)
    Leitsch, David
    Janssen, Brian D
    Kolarich, Daniel
    Johnson, Patricia J
    Duchene, Michael
    Griffith University Author(s)
    Kolarich, Daniel
    Year published
    2014
    Metadata
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    Abstract
    The enzyme flavin reductase 1 (FR1) from Trichomonas 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, FR1 has no close homologue in any other sequenced genome, but seven full-length and three truncated isoforms exist in the T. vaginalis ...
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    The enzyme flavin reductase 1 (FR1) from Trichomonas 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, FR1 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 FR1 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 FR1-mRNA structure in any of the strains studied, FR1 is not expressed in highly metronidazole-resistant strains. Transfection of a metronidazole-resistant clinical isolate (B7268), which does not express any detectable amounts of FR, with a plasmid bearing a functional FR1 gene nearly completely restored metronidazole sensitivity. Our results indicate that FR1 has a significant role in the emergence of metronidazole resistance in T. vaginalis.
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    Journal Title
    Molecular Microbiology
    Volume
    91
    Issue
    1
    DOI
    https://doi.org/10.1111/mmi.12455
    Subject
    Biological sciences
    Biochemistry and cell biology not elsewhere classified
    Agricultural, veterinary and food sciences
    Biomedical and clinical sciences
    Publication URI
    http://hdl.handle.net/10072/337597
    Collection
    • Journal articles

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