P-glycoprotein-9 and macrocyclic lactone resistance status in selected strains of the ovine gastrointestinal nematode, Teladorsagia circumcincta. Issue 1 (April 2018)

• Record Type: Journal Article
• Authors: Turnbull, Frank; Jonsson, Nicholas N.; Kenyon, Fiona; Skuce, Philip J.; Bisset, Stewart A.
• Is Part Of: International journal for parasitology. Volume 8:Issue 1(2018)
• Page Start: 70
• Page End: 80
• Publication Date: 2018-04
• Subjects: Teladorsagia circumcincta -- Anthelmintic resistance -- P-glycoprotein -- Ivermectin; Parasitic diseases -- Chemotherapy -- Periodicals; Drug resistance -- Periodicals; 616.96061
• DOI: 10.1016/j.ijpddr.2018.01.004
• Languages: English
• ISSNs: 2211-3207

Abstract

Abstract: 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.