The P-glycoprotein repertoire of the equine parasitic nematode Parascaris univalens.
Abstract: P-glycoproteins (Pgp) have been proposed as contributors to the widespread macrocyclic lactone (ML) resistance in several nematode species including a major pathogen of foals, Parascaris univalens. Using new and available RNA-seq data, ten different genomic loci encoding Pgps were identified and characterized by transcriptome-guided RT-PCRs and Sanger sequencing. Phylogenetic analysis revealed an ascarid-specific Pgp lineage, Pgp-18, as well as two paralogues of Pgp-11 and Pgp-16. Comparative gene expression analyses in P. univalens and Caenorhabditis elegans show that the intestine is the major site of expression but individual gene expression patterns were not conserved between the two nematodes. In P. univalens, PunPgp-9, PunPgp-11.1 and PunPgp-16.2 consistently exhibited the highest expression level in two independent transcriptome data sets. Using RNA-Seq, no significant upregulation of any Pgp was detected following in vitro incubation of adult P. univalens with ivermectin suggesting that drug-induced upregulation is not the mechanism of Pgp-mediated ML resistance. Expression and functional analyses of PunPgp-2 and PunPgp-9 in Saccharomyces cerevisiae provide evidence for an interaction with ketoconazole and ivermectin, but not thiabendazole. Overall, this study established reliable reference gene models with significantly improved annotation for the P. univalens Pgp repertoire and provides a foundation for a better understanding of Pgp-mediated anthelmintic resistance.
Publication Date: 2020-08-12 PubMed ID: 32788636PubMed Central: PMC7423980DOI: 10.1038/s41598-020-70529-6Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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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.
Cite This Article
APA
Gerhard AP, Krücken J, Heitlinger E, Janssen IJI, Basiaga M, Kornaś S, Beier C, Nielsen MK, Davis RE, Wang J, von Samson-Himmelstjerna G.
(2020).
The P-glycoprotein repertoire of the equine parasitic nematode Parascaris univalens.
Sci Rep, 10(1), 13586.
https://doi.org/10.1038/s41598-020-70529-6 Publication
Researcher Affiliations
- Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
- Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
- Institute of Biology, Molecular Parasitology, Humboldt-Universität Zu Berlin, Berlin, Germany.
- Leibniz Institute for Zoo and Wildlife Research, Research Group Ecology and Evolution of Parasite Host Interactions, Berlin, Germany.
- Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
- Department of Zoology and Animal Welfare, University of Agriculture in Kraków, Kraków, Poland.
- Department of Zoology and Animal Welfare, University of Agriculture in Kraków, Kraków, Poland.
- Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
- Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, USA.
- Department of Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, USA.
- Department of Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, USA.
- Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN, USA.
- Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Berlin, Germany. samson.georg@fu-berlin.de.
MeSH Terms
- ATP Binding Cassette Transporter, Subfamily B, Member 1 / classification
- ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
- ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
- Animals
- Antiparasitic Agents / pharmacology
- Ascaridida Infections / drug therapy
- Ascaridida Infections / parasitology
- Ascaridoidea / genetics
- Ascaridoidea / metabolism
- Ascaridoidea / physiology
- Drug Resistance / drug effects
- Drug Resistance / genetics
- Helminth Proteins / classification
- Helminth Proteins / genetics
- Helminth Proteins / metabolism
- Horses / parasitology
- Ivermectin / pharmacology
- Phylogeny
- Reverse Transcriptase Polymerase Chain Reaction
- Sequence Analysis, DNA / methods
- Sequence Analysis, RNA / methods
- Sequence Analysis, RNA / statistics & numerical data
- Transcriptome
Conflict of Interest Statement
The authors declare no competing interests.
References
This article includes 93 references
Citations
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