The P-glycoprotein repertoire of the equine parasitic nematode Parascaris univalens.
ATP Binding Cassette Transporter, Subfamily B, Member 1
/ classification
Animals
Antiparasitic Agents
/ pharmacology
Ascaridida Infections
/ drug therapy
Ascaridoidea
/ genetics
Drug Resistance
/ drug effects
Helminth Proteins
/ classification
Horses
/ parasitology
Ivermectin
/ pharmacology
Phylogeny
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, DNA
/ methods
Sequence Analysis, RNA
/ methods
Transcriptome
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
12 08 2020
12 08 2020
Historique:
received:
03
04
2020
accepted:
21
07
2020
entrez:
14
8
2020
pubmed:
14
8
2020
medline:
29
12
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32788636
doi: 10.1038/s41598-020-70529-6
pii: 10.1038/s41598-020-70529-6
pmc: PMC7423980
doi:
Substances chimiques
ATP Binding Cassette Transporter, Subfamily B, Member 1
0
Antiparasitic Agents
0
Helminth Proteins
0
Ivermectin
70288-86-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13586Références
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