The transcription factor SKN-1 and detoxification gene ugt-22 alter albendazole efficacy in Caenorhabditis elegans
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 β-tubulin is a we...
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2211320718300137 |
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doaj-948716628345493f9eefbda58d0d9b6c2020-11-24T23:55:38ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072018-08-0182312319The transcription factor SKN-1 and detoxification gene ugt-22 alter albendazole efficacy in Caenorhabditis elegansPauline Fontaine0Keith Choe1Department of Biology, University of Florida, Gainesville, FL 32611, USACorresponding author. Department of Biology and Genetics Institute, University of Florida, Newell Drive, Gainesville, FL 32611, USA.; Department of Biology, University of Florida, Gainesville, FL 32611, USAParasitic 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 β-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 EC50 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 EC50 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. Keywords: Detoxification, Albendazole, Drug resistance, Parasite, Anthelmintichttp://www.sciencedirect.com/science/article/pii/S2211320718300137 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pauline Fontaine Keith Choe |
spellingShingle |
Pauline Fontaine Keith Choe The transcription factor SKN-1 and detoxification gene ugt-22 alter albendazole efficacy in Caenorhabditis elegans International Journal for Parasitology: Drugs and Drug Resistance |
author_facet |
Pauline Fontaine Keith Choe |
author_sort |
Pauline Fontaine |
title |
The transcription factor SKN-1 and detoxification gene ugt-22 alter albendazole efficacy in Caenorhabditis elegans |
title_short |
The transcription factor SKN-1 and detoxification gene ugt-22 alter albendazole efficacy in Caenorhabditis elegans |
title_full |
The transcription factor SKN-1 and detoxification gene ugt-22 alter albendazole efficacy in Caenorhabditis elegans |
title_fullStr |
The transcription factor SKN-1 and detoxification gene ugt-22 alter albendazole efficacy in Caenorhabditis elegans |
title_full_unstemmed |
The transcription factor SKN-1 and detoxification gene ugt-22 alter albendazole efficacy in Caenorhabditis elegans |
title_sort |
transcription factor skn-1 and detoxification gene ugt-22 alter albendazole efficacy in caenorhabditis elegans |
publisher |
Elsevier |
series |
International Journal for Parasitology: Drugs and Drug Resistance |
issn |
2211-3207 |
publishDate |
2018-08-01 |
description |
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 β-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 EC50 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 EC50 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. Keywords: Detoxification, Albendazole, Drug resistance, Parasite, Anthelmintic |
url |
http://www.sciencedirect.com/science/article/pii/S2211320718300137 |
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