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Expression data from Caenorhabditis elegans exposed to ivermectin

ABSTRACT: We have investigated the transcriptomic response of the model nematode Caenorhabditis elegans to ivermectin (IVM); an important anthelmintic for human and animal parasite control. The transcriptomic response of the mutant strain DA1316 avr-14(ad1302); avr-15(ad1250); glc-1(pk54), which is highly resistant to ivermectin due to null mutations in three glutamate-gated chloride channel subunits, was examined. Despite the resistant nature of this strain, pharyngeal pumping rate was decreased following 4 hrs exposure to 100ng/ml and 1μg/ml ivermectin resulting in significant change in the expression level of genes associated with a fasting response.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE22660 | GEO | 2011/04/01

SECONDARY ACCESSION(S): PRJNA128009

REPOSITORIES: GEO

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Project description:Ascarid parasites infect a variety of hosts, and control measures rely heavily on anthelmintics raising concerns for anthelmintic resistance. Parascaris spp., the equine ascarid, is the only ascarid with documented substantial drug resistance. Elucidating drug responses of susceptible parasites may lead to further understanding of anthelmintic resistance mechanisms, identifying alternative drug targets, and parameters for slowing the development of resistance among other ascarid species. The purpose of this study was to examine the response of anthelmintic naïve Parascaris spp. to in vitro drug exposure using transcriptomic analyses and quantitative PCR. Adult Parascaris spp. worms were obtained at necropsy from foals born into a herd kept without anthelmintic treatment. Adult worms were maintained in Roswell-Park Memorial medium 1640. The drugs employed were oxibendazole (OBZ) and ivermectin (IVM), and 10-fold serial dilutions were prepared. Optimum drug concentration and exposure length were determined using a worm viability assessment method. Subsequently, RNA-seq analysis identified genes with significantly different expression between drug treated and control groups. Finally, a selection of the significant genes was further investigated using qPCR in a repeat drug exposure trial. Following initial viability assessments, OBZ (10 μg/mL) for 24 hours and IVM (1 μg/mL) for three hours were the conditions employed. RNA-seq analysis revealed a total of 88 transcripts with significantly (α=0.01) different expression between all drug treated and control worms. The top five genes selected for further analysis were snap25, cytochrome p450, kelch10, sup9, and ferm. Gene functionalities are related to muscle contraction, detoxification and exocytotic events, and regulatory processes. qPCR did not identify any significant differences between groups, but this may be due to the lack of method sensitivity. The results of RNA-seq analysis and gene function warrant further investigation and their role in ascarid xenobiotic responses.

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Expression data from Caenorhabditis elegans exposed to ivermectin

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