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Parasites & vectors2020; 13(1); 342; doi: 10.1186/s13071-020-04212-0

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

Abstract: Parascaris univalens is a pathogenic parasite of foals and yearlings worldwide. In recent years, Parascaris spp. 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 adult P. univalens worms after in vitro exposure 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 M, 10 M, 10 M), pyrantel citrate (10 M, 10 M, 10 M), thiabendazole (10 M, 10 M, 10 M) or without anthelmintics (control) at 37 °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 subunit lgc-37, which was upregulated only in worms exposed to 10 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 in P. univalens and future work should be focused on characterising these candidate genes to further explore their potential involvement in drug metabolism and anthelmintic resistance.
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Publication Date: 2020-07-09 PubMed ID: 32646465PubMed Central: PMC7346371DOI: 10.1186/s13071-020-04212-0Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explored the reactions of a particular horse pathogen, Parascaris univalens, to different doses of common deworming drugs. The results showed varying degrees of resilience dependent on the drug and dosage, with some genes in the worm apparently adapting to resist the drugs.

Introduction

  • Parascaris univalens is a pathogenic parasite causing disease in young horses (foals and yearlings).
  • These worms have developed resistance recently to several commonly used deworming drugs, or anthelmintics, but how they do this is not well understood.
  • The study aims to further understand this resistance by studying the genetic responses of these worms when exposed to different concentrations of three deworming drugs.

Methods

  • The worms were harvested from two foals that had naturally contracted the parasite and had not been previously treated with anthelmintics.
  • These worms were then exposed to media containing either ivermectin, pyrantel citrate, or thiabendazole or left untreated (control).
  • After 24 hours of drug exposure, the survival of the worms was verified and RNA extracted to understand their genetic responses to the drugs.

Results

  • All worms survived the incubation, but with different levels of viability based on the specific drug and its concentration.
  • Analysis of gene expression revealed that specific genes were either downregulated or upregulated after exposure to the different drugs.
  • These genes are part of metabolic pathways, including the short-chain dehydrogenase/reductase superfamily (SDR), the flavin containing monooxygenase superfamily (FMO), the cytochrome P450-family (CYP), and make up part of the cell membrane transport structures (major facilitator superfamily (MFS), and solute carrier superfamily (SLC)).
  • Generally, these genes, which are also targets of the anthelmintics used, were either upregulated or downregulated in a nonspecific pattern, with the exception of the GABA receptor subunit lgc-37, which was only upregulated in worms exposed to ivermectin.

Conclusions

  • The study reports, for the first time, the response of the lgc-37 gene and members of several superfamilies (FMO, SDR, MFS, SLC) in Parascaris univalens to exposure to anthelmintics.
  • Future research will focus on these genes to better understand their role in the worms’ ability to metabolize the drugs and develop resistance.

Cite This Article

APA
Martin F, Dube F, Karlsson Lindsjö O, Eydal M, Höglund J, Bergström TF, Tydén E. (2020). Transcriptional responses in Parascaris univalens after in vitro exposure to ivermectin, pyrantel citrate and thiabendazole. Parasit Vectors, 13(1), 342. https://doi.org/10.1186/s13071-020-04212-0

Publication

Parasites & vectors
ISSN: 1756-3305
NlmUniqueID: 101462774
Country: England
Language: English
Volume: 13
Issue: 1
Pages: 342
PII: 342

Researcher Affiliations

Martin, Frida
  • Division of Parasitology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7036, 750 07, Uppsala, Sweden. Frida.Martin@slu.se.
Dube, Faruk
  • Division of Parasitology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7036, 750 07, Uppsala, Sweden.
Karlsson Lindsjö, Oskar
  • SLU-Global Bioinformatics Centre, Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Box 7023, 750 07, Uppsala, Sweden.
Eydal, Matthías
  • Institute for Experimental Pathology at Keldur, University of Iceland, Keldnavegur 3, 112, Reykjavik, Iceland.
Höglund, Johan
  • Division of Parasitology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7036, 750 07, Uppsala, Sweden.
Bergström, Tomas F
  • Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Box 7023, 750 07, Uppsala, Sweden.
Tydén, Eva
  • Division of Parasitology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7036, 750 07, Uppsala, Sweden.

MeSH Terms

  • Animals
  • Anthelmintics / metabolism
  • Anthelmintics / pharmacology
  • Ascaridida Infections / metabolism
  • Ascaridida Infections / veterinary
  • Ascaridoidea / drug effects
  • Ascaridoidea / metabolism
  • Drug Resistance
  • Horse Diseases / metabolism
  • Horse Diseases / parasitology
  • Horses
  • Ivermectin / metabolism
  • Ivermectin / pharmacology
  • Pyrantel / analogs & derivatives
  • Pyrantel / metabolism
  • Pyrantel / pharmacology
  • Thiabendazole / metabolism
  • Thiabendazole / pharmacology
  • Transcriptome / drug effects

Grant Funding

  • 942-2015-508 / Svenska Forskningsru00e5det Formas

Conflict of Interest Statement

The authors declare that they have no competing interests.

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