P-glycoprotein-9 and macrocyclic lactone resistance status in selected strains of the ovine gastrointestinal nematode, Teladorsagia circumcincta
| Autor: | Fiona Kenyon, S.A. Bisset, Nicholas N. Jonsson, Frank Turnbull, Philip Skuce |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
ATP Binding Cassette Transporter Subfamily B Genotyping Techniques Sheep Diseases Single-nucleotide polymorphism P-glycoprotein Biology Polymorphism Single Nucleotide Article lcsh:Infectious and parasitic diseases Feces 03 medical and health sciences Negative selection Ivermectin Ostertagiasis Complementary DNA parasitic diseases medicine Animals Parasite hosting lcsh:RC109-216 Pharmacology (medical) Parasite Egg Count Gene Anthelmintic resistance Anthelmintics Pharmacology Genetics Genome Helminth Genetic diversity Sheep Ostertagia Genetic Variation Drug Resistance Multiple United Kingdom Teladorsagia circumcincta 030104 developmental biology Infectious Diseases Parasitology medicine.drug |
| Zdroj: | International Journal for Parasitology: Drugs and Drug Resistance International Journal for Parasitology: Drugs and Drug Resistance, Vol 8, Iss 1, Pp 70-80 (2018) |
| ISSN: | 2211-3207 |
| DOI: | 10.1016/j.ijpddr.2018.01.004 |
| Popis: | The Teladorsagia circumcincta P-glycoprotein-9 (Tci-pgp-9) gene has previously been implicated in multiple-anthelmintic resistance in this parasite. Here we further characterise genetic diversity in Tci-pgp-9 and its possible role in ivermectin (IVM) and multi-drug resistance using two UK field isolates of T. circumcincta, one susceptible to anthelmintics (MTci2) and the other resistant to most available anthelmintics including IVM (MTci5). A comparison of full-length Tci-pgp-9 cDNA transcripts from the MTci2 and MTci5 isolates (∼3.8 kb in both cases) indicated that they shared 95.6% and 99.5% identity at the nucleotide and amino acid levels, respectively. Nine non-synonymous SNPs were found in the MTci5 sequences relative to their MTci2 counterparts. Twelve genomic sequence variants of the first internucleotide binding domain of Tci-pgp-9 were identified and up to 10 of these were present in some individual worms, strongly supporting previous evidence that amplification of this gene has occurred in T. circumcincta. On average, fewer distinct sequence variants of Tci-pgp-9 were present in individual worms of the MTci5 isolate than in those of the MTci2 isolate. A further reduction in the number of sequence variants was observed in individuals derived from an IVM-treated sub-population of MTci5. These findings suggest that Tci-pgp-9 was under purifying selection in the face of IVM treatment in T. circumcincta, with some sequence variants being selected against. Graphical abstract Image 1 Highlights • Tci-pgp-9 cDNA sequences from the MTci2 and MTci5 isolates shared 95.6% identity. • Comparison of Tci-pgp-9 sequences from MTci5 and MTci2 showed 9 non-synonymous SNPs. • Multiple Tci-pgp-9-IBDA sequence variants occurred in the majority of individual larvae. • Tci-pgp-9 appears to be under purifying selection after anthelmintics are applied. |
| Databáze: | OpenAIRE |
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