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Transcriptional responses in Parascaris univalens after in vitro exposure to ivermectin, pyrantel citrate and thiabendazole

Martin, Frida and Dube, Faruk and Karlsson Lindsjö, Oskar and Eydal, Matthias and Höglund, Johan and Bergström, Tomas (2020). Transcriptional responses in Parascaris univalens after in vitro exposure to ivermectin, pyrantel citrate and thiabendazole. Parasites and Vectors. 13 , 342 , 1-14
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Abstract

Background: Parascaris univalensis a pathogenic parasite of foals and yearlings worldwide. In recent years,Parascarisspp. worms have developed resistance to several of the commonly used anthelmintics, though currently the mechanisms behind this development are unknown. The aim of this study was to investigate the transcriptional responses in adultP. univalensworms afterin vitroexposure to different concentrations of three anthelmintic drugs, focusing on drug targets and drug metabolising pathways.Methods: Adult worms were collected from the intestines of two foals at slaughter. The foals were naturally infected and had never been treated with anthelmintics. Worms were incubated in cell culture media containing different concentrations of either ivermectin (10(-9) M, 10(-11) M, 10(-13) M), pyrantel citrate (10(-6) M, 10(-8) M, 10(-10) M), thiabendazole (10(-5) M, 10(-7) M, 10(-9) M) or without anthelmintics (control) at 37 degrees C for 24 h. After incubation, the viability of the worms was assessed and RNA extracted from the anterior region of 36 worms and sequenced on an Illumina NovaSeq 6000 system.Results: All worms were alive at the end of the incubation but showed varying degrees of viability depending on the drug and concentration used. Differential expression (Padj < 0.05 and log2 fold change >= 1 or <= - 1) analysis showed similarities and differences in the transcriptional response after exposure to the different drug classes. Candidate genes upregulated or downregulated in drug exposed worms include members of the phase I metabolic pathway short-chain dehydrogenase/reductase superfamily (SDR), flavin containing monooxygenase superfamily (FMO) and cytochrome P450-family (CYP), as well as members of the membrane transporters major facilitator superfamily (MFS) and solute carrier superfamily (SLC). Generally, different targets of the anthelmintics used were found to be upregulated and downregulated in an unspecific pattern after drug exposure, apart from the GABA receptor subunitlgc-37, which was upregulated only in worms exposed to 10(-9) M of ivermectin.Conclusions: To our knowledge, this is the first time the expression of lgc-37 and members of the FMO, SDR, MFS and SLC superfamilies have been described inP. univalensand future work should be focused on characterising these candidate genes to further explore their potential involvement in drug metabolism and anthelmintic resistance.

Authors/Creators:Martin, Frida and Dube, Faruk and Karlsson Lindsjö, Oskar and Eydal, Matthias and Höglund, Johan and Bergström, Tomas
Title:Transcriptional responses in Parascaris univalens after in vitro exposure to ivermectin, pyrantel citrate and thiabendazole
Year of publishing :2020
Volume:13
Article number:342
Number of Pages:14
Publisher:BMC
ISSN:1756-3305
Language:English
Publication Type:Journal article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Pathobiology
Keywords:Transcriptome, Anthelmintic resistance, RNA sequencing, Differential expression, lgc-37
URN:NBN:urn:nbn:se:slu:epsilon-p-107159
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-107159
Additional ID:
Type of IDID
DOI10.1186/s13071-020-04212-0
Web of Science (WoS)000551949500002
ID Code:17442
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Department of Biomedical Science and Veterinary Public Health
(VH) > Dept. of Animal Breeding and Genetics
Deposited By: SLUpub Connector
Deposited On:14 Sep 2020 08:58
Metadata Last Modified:14 Sep 2020 08:58

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