Genotypic characterisation of monepantel resistance in historical and newly derived field strains of Teladorsagia circumcincta

Turnbull, Frank; Devaney, Eileen; Morrison, Alison A.; Laing, Roz; Bartley, Dave

doi:10.1016/j.ijpddr.2019.10.002

Cited by 8 publications

(5 citation statements)

References 56 publications

(94 reference statements)

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“…Based on the results presented here, we can con rm that several different mutations in mptl-1 in H. contortus may be associated with the phenotype of monepantel resistance in the same population (Bagnall et al 2017) or in different populations, as reported for Teladorsagia circumcincta (Turnbull et al 2019), indicating that monepantel resistance is likely a quantitative trait. However, exon 11 of mptl-1 was particularly responsive to the selective pressure imposed by monepantel, as two different indels in the same region were observed in H. contortus-resistant isolates from two different sources ( eld derived and in vivo-selected) and in an independent resistant eld-derived population.…”

Section: Discussionsupporting

confidence: 77%

Polymorphisms in exon 11 of the mptl-1 gene and monepantel resistance in Haemonchus contortus

et al. 2022

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Because chemical treatments are the main strategy to control gastrointestinal nematodes in sheep, molecular tests may constitute an excellent tool for the early detection of the emergence of resistancerelated mutations. Thus, a polymerase chain reaction (PCR)-based genotyping assay followed by polyacrylamide gel electrophoresis (PAGE) was developed to detect polymorphisms in exon 11 of the acetylcholine receptor monepantel-1 gene (mptl-1) that were previously associated with monepantel resistance through a genome-wide study in Haemonchus contortus. DNA samples recovered from individual and pooled third-stage larvae from two susceptible eld-derived isolates and ve (three in vivoderived and two eld-derived) resistant populations were used. New polymorphisms, including a 6-bp deletion and a 3-bp insertion, were detected in resistant individuals. These indels, con rmed using sequencing of cloned PCR products, are predicted to result in amino acid changes in transmembrane domain 2 (TMD2) of the MPTL-1 protein. The two susceptible isolates showed only the presence of the wild-type allele (100%), whereas lower frequencies of the wild-type allele were detected in monepantelresistant populations (11.1 to 66.7%). These ndings report new polymorphisms in the mptl-1 gene, validate the results obtained through genomic mapping for monepantel resistance, and provide a PCRbased assay to genotype indels located in exon 11 of mptl-1 in H. contortus. Key FindingsFine-mapping of a locus associated with monepantel resistance using a genome-wide study in H. contortus.Design of a PCR-based assay to genotype indels in exon 11 of mptl-1 in H. contortus.

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Section: Discussionsupporting

confidence: 77%

Polymorphisms in exon 11 of the mptl-1 gene and monepantel resistance in Haemonchus contortus

et al. 2022

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“…This parasite is transmitted through the faecal-oral route and develops in the abomasum of the ovine host, where it causes pathology with mucosal damage and a protein-losing gastropathy associated with host inflammatory immune responses [18]. T. circumcincta resistance to anthelmintics is widespread [19,20], thus making control of this parasite in flocks highly challenging. Recent efforts by Nisbet and colleagues [21][22][23] have resulted in the development of an effective sub-unit vaccine against T. circumcincta, composed of a cocktail of eight recombinant proteins [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Infection with the sheep gastrointestinal nematode Teladorsagia circumcincta increases luminal pathobionts

Cortés

Wills

et al. 2020

Microbiome

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Background: The multifaceted interactions between gastrointestinal (GI) helminth parasites, host gut microbiota and immune system are emerging as a key area of research within the field of host-parasite relationships. In spite of the plethora of data available on the impact that GI helminths exert on the composition of the gut microflora, whether alterations of microbial profiles are caused by direct parasite-bacteria interactions or, indirectly, by alterations of the GI environment (e.g. mucosal immunity) remains to be determined. Furthermore, no data is thus far available on the downstream roles that qualitative and quantitative changes in gut microbial composition play in the overall pathophysiology of parasite infection and disease. Results: In this study, we investigated the fluctuations in microbiota composition and local immune microenvironment of sheep vaccinated against, and experimentally infected with, the 'brown stomach worm' Teladorsagia circumcincta, a parasite of worldwide socioeconomic significance. We compared the faecal microbial profiles of vaccinated and subsequently infected sheep with those obtained from groups of unvaccinated/infected and unvaccinated/ uninfected animals. We show that alterations of gut microbial composition are associated mainly with parasite infection, and that this involves the expansion of populations of bacteria with known pro-inflammatory properties that may contribute to the immunopathology of helminth disease. Using novel quantitative approaches for the analysis of confocal microscopy-derived images, we also show that gastric tissue infiltration of T cells is driven by parasitic infection rather than anti-helminth vaccination. Conclusions: Teladorsagia circumcincta infection leads to an expansion of potentially pro-inflammatory gut microbial species and abomasal T cells. This data paves the way for future experiments aimed to determine the contribution of the gut flora to the pathophysiology of parasitic disease, with the ultimate aim to design and develop novel treatment/control strategies focused on preventing and/or restricting bacterial-mediated inflammation upon infection by GI helminths.

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“…This parasite is transmitted through the faecal-oral route and develops in the abomasum of the ovine host where it causes pathology with mucosal damage and a protein-losing gastropathy associated with host inflammatory immune responses [18]. T. circumcincta resistance to anthelmintics is widespread [19][20], thus making control of this parasite in flocks highly challenging. Recent efforts by Nisbet and colleagues [21][22][23] have resulted in the development of an effective sub-unit vaccine against T. circumcincta, composed of a cocktail of 8 recombinant proteins [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Infection with the sheep gastrointestinal nematode Teladorsagia circumcincta increases luminal pathobionts

Cortés

Wills

et al. 2019

Preprint

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Background The multifaceted interactions between gastrointestinal (GI) helminth parasites, vertebrate host gut microbiota and the immune system are emerging as a key area of research within the field of host-parasite relationships. In spite of the plethora of data available on the impact that GI helminths exert on the composition of the gut microflora, whether alterations of microbial profiles are caused by direct parasite-bacteria interactions or, indirectly, by alterations of the GI environment (e.g. mucosal immunity), remains to be determined. Furthermore, no data is thus far available on the downstream roles that qualitative and quantitative changes in gut microbial composition play in the overall pathophysiology of parasite infection and disease. Results In this study, we investigated the fluctuations in microbiota composition and local immune microenvironment of sheep vaccinated against, and experimentally infected with, the ‘brown stomach worm’ Teladorsagia circumcincta, a parasite of worldwide socio-economic significance. We compared gut microbial profiles with those obtained from groups of unvaccinated/infected and unvaccinated/uninfected animals. We show that alterations to the gut microbial composition are associated mainly with parasite infection, and that this involves the expansion of populations of bacteria with known pro-inflammatory roles that may contribute to the immunopathology of helminth disease. Using novel quantitative approaches for the analysis of confocal microscopy-derived images we also show that gastric tissue infiltration of T cells is driven by parasitic infection rather than anti-helminth vaccination. Conclusions Teladorsagia circumcincta infection leads to an expansion of potentially pro-inflammatory gut microbial species and abomasal T cells. This data paves the way for future experiments aimed at determining the contribution of the gut flora to the pathophysiology of parasitic disease, with the ultimate aim to design and develop novel treatment/control strategies focused on preventing and/or restricting bacterial-mediated inflammation upon infection by gastrointestinal helminths.

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Genotypic characterisation of monepantel resistance in historical and newly derived field strains of Teladorsagia circumcincta

Cited by 8 publications

References 56 publications

Polymorphisms in exon 11 of the mptl-1 gene and monepantel resistance in Haemonchus contortus

Polymorphisms in exon 11 of the mptl-1 gene and monepantel resistance in Haemonchus contortus

Infection with the sheep gastrointestinal nematode Teladorsagia circumcincta increases luminal pathobionts

Infection with the sheep gastrointestinal nematode Teladorsagia circumcincta increases luminal pathobionts

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