The P-glycoprotein repertoire of the equine parasitic nematode Parascaris univalens.

The research examines the P-glycoprotein (Pgp) family in the equine nematode, Parascaris univalens. The study identifies and analyzes ten Pgps and explores their potential role in resistance against macrocyclic lactone (ML) treatment. Although the research did not find evidence of drug-induced Pgp upregulation, it did provide improved models for the Pgp repertoire in P. univalens, which will contribute to a better understanding of anthelmintic resistance.

Identification and Analysis of P-glycoproteins

• This research used RNA-sequencing data to identify and examine ten distinct genomic locations encoding P-glycoproteins (Pgps) in the nematode Parascaris univalens, a parasite common in horses.
• In sequencing these Pgps, the study also identified a new ascarid-specific Pgp lineage, Pgp-18, adding to the existing knowledge of nematode Pgps.
• The research also discovered two paralogues of Pgp-11 and Pgp-16, which further expands the known repertoire of Pgps in these parasites.

Gene Expression Analysis

• The study conducted comparative gene expression analyses between P. univalens and Caenorhabditis elegans to understand the genes’ behavior in different nematode species.
• It was found that the intestine is the major site of Pgp expression in both species.
• However, the specific patterns of individual gene expression were not identical between the two nematodes, showing a difference in gene function across species.

Investigation of Pgp-Mediated ML Resistance

• The study used RNA-Seq data to examine if MLs induce any upregulation of Pgps, which could indicate a drug resistance mechanism. However, the study didn’t find any significant upregulation after exposing adult P. univalens to ivermectin, an ML anthelmintic.
• The study also looked at the interaction of specific Pgps with various drugs. Results suggested interactions with ketoconazole and ivermectin, but not thiabendazole.

Improvement of Pgp Gene Models

• The research provided significantly improved and reliable reference gene models for P. univalens’s Pgp repertoire. This undertaking will assist future studies on the anthelmintic resistance mechanism in P. univalens.