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Resources » Paper

Fontaine P et al. (2018) Int J Parasitol Drugs Drug Resist "The transcription factor SKN-1 and detoxification gene ugt-22 alter albendazole efficacy in Caenorhabditis elegans."

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  • Comments on Fontaine P et al. (2018) Int J Parasitol Drugs Drug Resist "The transcription factor SKN-1 and detoxification gene ugt-22 alter albendazole efficacy in Caenorhabditis elegans." (0)

  • Overview

    PMID:
    29793058
    DOI:
    10.1016/j.ijpddr.2018.04.006
    Status:
    Publication type:
    Journal_article
    WormBase ID:
    WBPaper00054583

    Fontaine P, & Choe K (2018). The transcription factor SKN-1 and detoxification gene ugt-22 alter albendazole efficacy in Caenorhabditis elegans. Int J Parasitol Drugs Drug Resist, 8, 312-319. doi:10.1016/j.ijpddr.2018.04.006

    Parasitic nematodes infect over 1/4 th of the human population and are a major burden on livestock and crop production. Benzimidazole class anthelmintics are widely used to treat infections, but resistance is a widespread problem. Mutation of genes encoding the benzimidazole target -tubulin is a well-established mechanism of resistance, but recent evidence suggests that metabolism of the drugs may also occur. Our objective was to investigate contributions of the detoxification-response transcription factor SKN-1 to anthelmintic drug resistance using C. elegans. We find that skn-1 mutations alter EC<sub>50</sub> of the common benzimidazole albendazole in motility assays by 1.5-1.7 fold. We also identify ugt-22 as a detoxification gene associated with SKN-1 that influences albendazole efficacy. Mutation and overexpression of ugt-22 alter albendazole EC<sub>50</sub> by 2.3-2.5-fold. The influence of a nematode UGT on albendazole efficacy is consistent with recent studies demonstrating glucose conjugation of benzimidazoles.


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