Biology subjects

Jacquiet, P.

Publications and source records attributed to Jacquiet, P..

5 recordsLinked to original sources

bioRxiv2026

Sex-biased transcriptional rewiring of neuronal circuits associated with eprinomectin resistance in Haemonchus contortus

Anthelmintic resistance poses a critical threat to livestock health, with clinical failures of eprinomectin and other macrocyclic lactones documented in the gastrointestinal parasite Haemonchus contortus worldwide. We performed whole-genome Pool-seq of larvae and RNA-seq on adult male and female worms from five phenotypically characterised isolates - two eprinomectin-susceptible and three resistant - from dairy sheep in Southwest France. We identified a conserved macrocyclic lactone resistance locus on chromosome 5 and a putatively eprinomectin-specific locus on chromosome 4, alongside sex-specific transcriptomic responses linking genomic selection signatures to transcriptional phenotype. Predicted functions of selected and differentially expressed genes support reorganisation of neuronal circuits in drug responsiveness, including the kynurenine pathway producing neuroactive metabolites, further supported by quinolinic acid potentiating eprinomectin efficacy in larval assays. Despite geographic proximity, resistance appears to have evolved independently across farms. Together, these findings reveal a complex genetic architecture underlying eprinomectin resistance with implications for targeted diagnostics and resistance management.

genomics↗

bioRxiv2024

Larval motility assay using WMicrotracker: a high throughput test to discriminate between resistance and susceptibility to anthelmintic drugs in nematodes

Grazing ruminants suffer from various helminth infections particularly those caused by gastrointestinal nematode (GIN) parasites, which have a considerable impact on their welfare and productivity. Treatment predominantly relies on macrocyclic lactone (ML) anthelmintics, but their widespread application has led to the emergence of drug-resistant parasite populations worldwide. The standard method for detecting resistance, the Faecal Egg Count Reduction Test (FECRT), is susceptible to misinterpretation, leading to flawed management decisions that undermine parasite control efforts. Thus, there is a pressing need for robust resistance detection methods in field parasites. We investigated the potential of the WMicrotrackerTM (WMi) motility assay, previously unexplored in ML resistance assessment. The assay first compared ivermectin (IVM) susceptibility among wild-type Bristol N2 (N2B), IVM-selected (IVR10), and nhr-8 loss-of-function (AE501; nhr8(ok186)) Caenorhabditis elegans strains. Dose-response curves indicated differences in IVM susceptibility among strains, with IVR10 exhibiting a 2.12-fold decrease in sensitivity compared to N2B. Cross-resistance between IVM, moxidectin (MOX), and eprinomectin (EPR) was explored, demonstrating reduced susceptibility in IVR10 across all drugs compared to N2B. Further investigation was conducted using Haemonchus contortus (H. contortus) to assess the assays applicability in discriminating susceptible from resistant isolates. Results revealed significant differences in drug potency between susceptible and resistant isolates, with MOX demonstrating the highest efficacy. Resistance factors (RF) highlighted the substantial resistance of the resistant isolate to EPR. The motility assay effectively discriminated susceptible from resistant isolates in both C. elegans and H. contortus. Our findings demonstrate, for the first time, the relevance of the motility assay by WMi as a functional indicator of resistance in nematodes, offering a promising avenue for detecting resistance to MLs. This research sheds light on a novel approach for monitoring drug resistance, vital for effective parasite management strategies.

pharmacology and toxicology↗

bioRxiv2023

Cross-transmission of resistant gastrointestinal nematodes between wildlife and transhumant sheep

Wild and domestic ungulates can be infected with the same species of gastrointestinal parasitic nematodes. These parasites have free-living stages in the environment that contribute to the ease of transmission among different host species. In addition, gastrointestinal nematodes have developed resistance to anthelmintics which is now considered a major problem for the livestock sector. In a context where wild and domestic ungulates share the same pastures, the maintenance and circulation of resistant gastrointestinal nematodes between species have rarely been explored. In the European Alps, domestic sheep are driven to high-altitude summer pastures and live in sympatry with wild ungulates for several months each year. In this study, we investigated the nemabiome of domestic sheep and Alpine ibex, Capra ibex, in three different areas of the French Alps to evaluate parasite circulation between the two host species. The Alpine ibex is a protected mountain ungulate that is phylogenetically related to sheep and hosts nematode species common to sheep. Using internal transcribed spacer 2 (ITS-2) nemabiome metabarcoding, we found sheep and ibex share similar gastrointestinal nematodes, except for a few species such as Marshallagia marshalli and Trichostrongylus axei. This suggests that the long-term co-occurrence of sheep and ibex on mountain pastures has promoted the exchange of gastrointestinal nematodes between the two hosts. Based on the sequencing of the isotype 1 of the beta tubulin gene, associated with benzimidazole resistance, we found resistant nematodes in all sheep flocks and in all ibex populations. Our results demonstrated that ibex can host and shed resistant strains before transhumant sheep arrive on pastures, and thus could act as a refuge or even contribute to maintaining resistant gastrointestinal nematodes. The relative role of ibex in the maintenance and circulation of resistant strains in sheep remain to be determined.

ecology↗

bioRxiv2020

Strongyle-resistant sheep express their potential across environments and leave limited scope for parasite plasticity

IntroductionDrug-resistant parasites threaten livestock production. Breeding more resistant hosts could be a sustainable control strategy. Environmental variation may however alter the expression of genetic potential and directional selection toward host resistance could initiate an arms race between the host and its parasites. Methods and ResultsWe created sheep lines with high or low resistance to Haemonchus contortus. We first exposed both lines to chronic stress or to the infection by another parasite Trichostrongylus colubriformis, to test for genotype-by-environment and genotype-by-parasite species interactions respectively. Overall, between-line divergence remained significant across environmental perturbations. But we found that the impact of chronic stress on H. contortus infection varied among families and that divergence was reduced during infection by T. colubriformis. Second, we quantified genomic and transcriptomic differences in H. contortus worms collected from both lines to identify components of an arms race. We found no evidence of genetic differentiation between worms from each line. But survival to more resistant hosts was associated with enhanced expression of cuticle collagen coding genes. DiscussionBreeding for resistance hence remains a sustainable strategy that requires to anticipate the effects of environmental perturbations and to monitor worm populations.

evolutionary biology↗

bioRxiv2017

Risk factor analysis of equine strongyle resistance to anthelmintics

Intestinal strongyles are the most problematic endoparasites of equids as a result of their wide distribution and the spread of resistant isolates throughout the world. While abundant literature can be found on the extent of anthelmintic resistance across continents, empirical knowledge about associated risk factors is missing. This study brought together results from anthelmintic efficacy testing and risk factor analysis to provide evidence-based guidelines in the field. It involved 688 horses from 39 French horse farms and riding schools to both estimate Faecal Egg Count Reduction (FECR) after anthelmintic treatment and to interview farm and riding school managers about their practices. Risk factors associated with reduced anthelmintic efficacy in equine strongyles were estimated across drugs using a marginal modelling approach. Results demonstrated ivermectin efficacy (96.3% FECR), the inefficacy of fenbendazole (42.8% FECR) and an intermediate profile for pyrantel (90.3% FECR). Risk factor analysis provided support to advocate for FEC-based treatment regimens combined with individual anthelmintic dosage and the enforcement of tighter biosecurity around horse introduction that contributed to lower drug resistance risk by 1.75. Premises falling under this typology also relied more on their veterinarians suggesting they play an important role in the sustainability of anthelmintic usage. Similarly, drug resistance risk was halved in premises with frequent pasture rotation and with stocking rate below five horses/ha. This is the first empirical risk factor analysis for anthelmintic resistance in equids, whose findings should guide the implementation of more sustained strongyle management in the field.

zoology↗