Genetic variants and increased expression of Parascaris equorum P-glycoprotein-11 in populations with decreased ivermectin susceptibility.
Authors: Janssen I Jana I, Krücken Jürgen, Demeler Janina, Basiaga Marta, Kornaś Sławomir, von Samson-Himmelstjerna Georg
Journal: PloS one
Summary
# Editorial Summary: Ivermectin Resistance in Parascaris equorum Ivermectin and other macrocyclic lactones remain critical tools for controlling equine parasites, yet treatment failures are becoming increasingly common in *Parascaris equorum* populations worldwide, with the underlying resistance mechanisms remaining poorly characterised. Researchers cloned and sequenced two P-glycoprotein genes (PeqPgp-11 and PeqPgp-16) from *P. equorum*, identifying them as orthologues of known nematode transporter proteins, then used quantitative PCR and genetic sequencing to compare expression patterns and DNA sequences between parasite populations with varying ivermectin susceptibility. The key finding was that pre-adult worms from ivermectin-resistant populations displayed both significantly elevated PeqPgp-11 messenger RNA expression and three specific single nucleotide polymorphisms (SNPs) causing amino acid changes in the Pgp-11 protein, whereas embryonated eggs showed genetic differences but no expression changes. These discoveries suggest that P-glycoprotein-11 plays a meaningful role in ivermectin resistance development—particularly in the motile life-cycle stages exposed to drug pressure—and the three identified SNPs represent promising genetic markers for reliably diagnosing resistance in field populations before treatment failure occurs. For practitioners, this research provides a foundation for molecular diagnostic testing that could enable targeted parasite management strategies and help preserve macrocyclic lactone efficacy through more informed selective treatment protocols.
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Practical Takeaways
- •Ivermectin resistance in P. equorum may be developing through P-glycoprotein overexpression and genetic mutations; consider fecal egg count monitoring to detect emerging resistance
- •Diagnostic testing for specific Pgp-11 SNPs could help identify resistant parasite populations before treatment failures occur, allowing for timely management strategy changes
- •Understanding the genetic basis of resistance supports development of improved anthelmintic strategies and rotation protocols on farms showing treatment failures
Key Findings
- •Three single nucleotide polymorphisms (SNPs) in PeqPgp-11 correlated with decreased ML susceptibility in P. equorum populations
- •PeqPgp-11 showed significantly higher expression in gut tissue and statistically significant overexpression in IVM-resistant pre-adult worms
- •P-glycoprotein-11 involvement in ivermectin resistance mechanisms identified through comparative sequence analysis and expression studies
- •SNPs in PeqPgp-11 identified as promising diagnostic candidates for detection of macrocyclic lactone resistance in equine parasites