title: Transcriptomic evaluation of the nicotinic acetylcholine receptor pathway in levamisole-resistant and -sensitive Oesophagostomum dentatum.
abstract: Nematode anthelminthic resistance is widespread for the 3 major drug classes commonly used in agriculture: benzamidazoles, macrocyclic lactones, and nicotinic agonists e.g. levamisole. In parasitic nematodes the genetics of resistance is unknown other than to the benzimidazoles which primarily involve a single gene. In previous work with a levamisole resistant Oesophagostomum dentatum isolate, the nicotinic acetylcholine receptor (nAChR) exhibited decreased levamisole sensitivity. Here, using a transcriptomic approach on the same isolate, we investigate whether that decreased nAChR sensitivity is achieved via a 1-gene mechanism involving 1 of 27 nAChR pathway genes. 3 nAChR receptor subunit genes exhibited ≥2-fold change in transcript abundance: acr-21 and acr-25 increased, and unc-63 decreased. 4 SNPs having a ≥2-fold change in frequency were also identified. These data suggest that resistance is likely polygenic, involving modulated abundance of multiple subunits comprising the heteropentameric nAChR, and is not due to a simple 1-gene mechanism.
authors: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
authors: Nathan M
authors: NM
authors: Romine
authors: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
authors: Richard J
authors: RJ
authors: Martin
authors: Department of Veterinary Pathology, Iowa State University, Ames, IA 50011, USA. Electronic address: jbeetham@iastate.edu.
authors: Jeffrey K
authors: JK
authors: Beetham
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000378:metabolism*; D004351:Drug Resistance; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D007978:Levamisole / Q000378:metabolism*; D009815:Oesophagostomum / Q000187:drug effects*; D021122:Protein Subunits / Q000235:genetics; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics
chemical_list: D000871:Anthelmintics; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D007978:Levamisole
keywords: Levamisole; Nodular worm; Resistance; nAChR