Claerebout, Edwin

De Graef, Jessie

Geldhof, Peter

Mitreva, M

Vercruysse, Jozef

Wolstenholme, A

English

Ghent University Academic Bibliography

Abstract 1  Jessie De Graef   Ghent University 	   1/1	  Glutamate-gated chloride genes in ivermectin-resistant Cooperia oncophora De Graef J.1, Claerebout E.1, Vercruysse J.1, Wolstenholme A.2, Mitreva M.3, Geldhof P.1 1Laboratory for Parasitology, Faculty of Veterinary Medicine, Ghent University, Belgium. 2Department of Infectious Diseases, University of Georgia, Athens, Georgia, United States of America. 3Department of Genetics, The Genome Center, Washington University School of Medicine, St. Louis, Missouri, United States of America. The glutamate-gated chloride-channels (GluCl’s) are only found in invertebrates and are important target sites for macrocyclic lactones (ML’s). Changes at the protein level of the ML-target sites may induce resistance to the anthelmintics. In the free living nematode Caenorhabditis elegans, six genes have been identified that encode GluCl subunits. In this study we analysed the transcriptome database of C. oncophora for genes that encode possible GluCl subunits. We could identify homologues of Avr-14, Glc-2, Glc-4 and a parasite-specific GluCl gene, i.e. Glc-6. By reverse-transcriptase PCR we determined that all these genes are equally expressed in all life stages (L1, L2, L3, L4, Male, Female) of C. oncophora, except for a lower transcription in the eggs. Full-length cDNA sequences of Glc-4 and Glc-6 were generated from a susceptible and ivermectin-resistant isolate and subsequently analyzed for the presence of polymorphisms. In addition, quantitative real-time PCR’s were performed to compare the mRNA transcription levels between susceptible and resistant C. oncophora adult worms. For Glc-4 no constitutive or inducible changes could be observed. In contrast, we found a significant downregulation of Glc-6 transcription levels in resistant adult worms compared to susceptible ones, similar as previously described for Avr-14. The search for relevant mutations, indicating ivermectin-resistance in these GluCl genes is currently ongoing. 

Glutamate-gated chloride genes in ivermectin-resistant Cooperia oncophora

https://biblio.ugent.be/publication/2007044/file/2007046.pdf

Glutamate-gated chloride genes in ivermectin-resistant Cooperia oncophora

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Ghent University Academic Bibliography