Scientific reports, 2020-08, Vol.10 (1), p.13586, Article 13586
2020
Details
- Autor(en) / Beteiligte
- Titel
- The P-glycoprotein repertoire of the equine parasitic nematode Parascaris univalens
- Ist Teil von
- Scientific reports, 2020-08, Vol.10 (1), p.13586, Article 13586
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-020-70529-6Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7423980
- Format
- –
- Schlagworte
- Animals, Anthelmintic agents, Antiparasitic Agents - pharmacology, Ascaridida Infections - drug therapy, Ascaridida Infections - parasitology, Ascaridoidea - genetics, Ascaridoidea - metabolism, Ascaridoidea - physiology, 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, Drug Resistance - drug effects, Drug Resistance - genetics, Gene expression, Helminth Proteins - classification, Helminth Proteins - genetics, Helminth Proteins - metabolism, Horses - parasitology, Intestine, Ivermectin, Ivermectin - pharmacology, Ketoconazole, P-Glycoprotein, Parascaris univalens, Pest resistance, Phylogeny, Reverse Transcriptase Polymerase Chain Reaction, Ribonucleic acid, RNA, Sequence Analysis, DNA - methods, Sequence Analysis, RNA - methods, Sequence Analysis, RNA - statistics & numerical data, Thiabendazole, Transcriptome