Biology subjects

Guegnard, F.

Publications and source records attributed to Guegnard, F..

3 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↗

bioRxiv2019

Lupin (Lupinus sp.) seeds exert anthelmintic activity associated with their alkaloid content

The growing expansion range of drug resistant parasitic nematode populations threatens the sustainability of ruminant farming worldwide. In this context, nutraceuticals, i.e. feed that would both fulfil dietary requirements while ensuring parasite control, would contribute to increase farming sustainability in developed and low resource settings. In this study, we characterized the anthelmintic potential of lupin seed extracts against major ruminant trichostrongylids, i.e. H. contortus and T. circumcincta. Our observations showed that total seed extracts from commercially available lupin varieties significantly inhibited larval migration. This anthelmintic effect was sustained on multidrug resistant field isolate and across parasite species and was mediated by the seed alkaloid content. Analytical chemistry revealed a set of four lupanine and sparteine-derivatives with anthelmintic activity and electrophysiology assays on recombinant nematode acetylcholine receptors suggested an antagonistic mode of action for lupin alkaloids. While commercial lupin seeds did not exert direct anthelmintic effect in H. contortus infected lupin-fed ewes and goats, it significantly dampened blood production losses suffered by goats. Lupin seed extracts hence provide a working basis for the development of novel anthelmintic compounds able to break drug resistance in the field, while they could be used to increase the resilience of infected dairy ruminants.

pharmacology and toxicology↗

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↗