Mutations in the Hco-mptl-1 gene in a field-derived monepantel-resistant isolate of Haemonchus contortus

International Journal for Parasitology. Drugs and Drug Resistance
Neil H BagnallAndrew C Kotze

Abstract

Resistance to the anthelmintic drug monepantel (Zolvix®) has emerged in parasitic worms infecting sheep and goats. The mechanism of resistance in these cases is unknown. The drug targets nicotinic acetylcholine receptors belonging to the nematode-specific DEG-3 subfamily. We examined the receptor gene, Hco-mptl-1, in a highly Zolvix®-resistant and a -susceptible isolate of the parasitic nematode Haemonchus contortus. cDNA coding for the full length receptor protein (Hco-MPTL-1) was present in all clones prepared from a pool of susceptible larvae (21/21 clones) and approximately 50% of those from the resistant isolate (17/33). On the other hand, the remaining clones from the resistant isolate showed various mutations that resulted in truncated predicted proteins, missing at least one transmembrane domain. The most common mutation (11/33 clones) resulted in the retention of intron 15, a premature stop codon, and a truncated protein. Sequencing of intron 15 genomic DNA showed very few SNPs in susceptible larvae and in 12/18 clones from resistant larvae, alongside the presence of at least 17 SNPs in the remaining resistant clones. The present study shows that the highly resistant isolate has a number of mutations in the drug target...Continue Reading

Citations

Aug 16, 2019·Parasites & Vectors·Simone Cristina Méo NiciuraAlessandro Francisco Talamini do Amarante
Dec 22, 2017·Emerging Topics in Life Sciences·Adrian J Wolstenholme, Cedric Neveu
Feb 5, 2021·Animals : an Open Access Journal From MDPI·Konstantinos V ArsenopoulosElias Papadopoulos
Apr 3, 2021·International Journal for Parasitology. Drugs and Drug Resistance·Candela CantonMariana Ballent
Nov 30, 2020·International Journal for Parasitology. Drugs and Drug Resistance·Steffen R HahnelDaniel Kulke
Dec 12, 2020·International Journal for Parasitology. Drugs and Drug Resistance·Andrew C KotzeRoger K Prichard
Jun 17, 2021·Revista brasileira de parasitologia veterinária = Brazilian journal of veterinary parasitology : Órgão Oficial do Colégio Brasileiro de Parasitologia Veterinária·José Vilemar de Araújo-FilhoClaudia Maria Leal Bevilaqua

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Methods Mentioned

BETA
PCR

Software Mentioned

BLAST
MEGA6

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Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.