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Home / Equine Research Bank / Int J Parasitol Drugs Drug Resist / Transgenically expressed Parascaris P-glycoprotein-11 can mo...
International journal for parasitology. Drugs and drug resistance2015; 5(2); 44-47; doi: 10.1016/j.ijpddr.2015.03.003

Transgenically expressed Parascaris P-glycoprotein-11 can modulate ivermectin susceptibility in Caenorhabditis elegans.

Abstract: P-glycoproteins (Pgps) are suspected to mediate drug extrusion in nematodes contributing to macrocyclic lactone resistance. This association was recently shown for Parascaris Pgp-11. Ivermectin resistance was correlated with the presence of three pgp-11 single nucleotide polymorphisms and/or increased pgp-11 mRNA levels. In the present study, the ability of Pgp-11 to modulate ivermectin susceptibility was investigated by its expression in a pgp-11-deficient Caenorhabditis elegans strain. Expression of Parascaris pgp-11 in two transgenic lines significantly decreased ivermectin susceptibility in a motility (thrashing) assay conducted in liquid medium. The EC50 values increased by 3.2- and 4.6-fold in the two lines relative to a transgenic control strain. This is the first report on the successful functional analysis of a parasitic nematode Pgp in the model organism C. elegans.
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Publication Date: 2015-04-08 PubMed ID: 25905032PubMed Central: PMC4401813DOI: 10.1016/j.ijpddr.2015.03.003Google Scholar: Lookup
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  • Journal Article
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  • Non-U.S. Gov't

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 research investigates the role of Pgp-11—a protein thought to be associated with drug resistance—in regulating the resistance of a specific type of worm (C. elegans) to a drug called ivermectin. It finds that expressing this protein in the worm makes them more resistant to the drug.

Introduction to the Research

  • The study focuses on understanding how a protein known as P-glycoproteins, or Pgps, contribute to drug resistance in nematodes—specifically their resistance to macrocyclic lactone (including ivermectin).
  • Pgps are believed to mediate drug extrusion in nematodes, meaning they could play a contributing role in making nematodes resistant or immune to certain medications.

Objectives and Methodology

  • The particular Pgp protein being studied here is Pgp-11, which was recently found to be associated with ivermectin resistance.
  • This resistance was linked to the presence of certain mutations (single nucleotide polymorphisms) in the Pgp-11 protein or an increase in the levels of the mRNA that codes this protein.
  • The research involved investigating the ability of Pgp-11 to modulate ivermectin susceptibility by expressing it in a worm strain (Caenorhabditis elegans) that naturally lacks this protein (pgp-11-deficient).

Results and Findings

  • The results of the study found that the expression of the Parascaris pgp-11 in two transgenic lines of C. elegans significantly decreased their susceptibility to ivermectin.
  • This reduced susceptibility was demonstrated via a motility (thrashing) assay conducted in liquid medium.
  • The EC50 values (the concentration of the drug at which 50% of the maximal effect is observed) for these worms increased by 3.2 and 4.6 times respectively when compared to a control group. This indicates that a higher concentration of ivermectin was required to affect the worms expressing the Parascaris pgp-11, demonstrating increased resistance to the drug.

Significance of the Research

  • This research marks the first successful functional analysis of a parasitic nematode Pgp protein in the model organism C. elegans.
  • The findings contribute to our understanding of how Pgp proteins can regulate drug resistance in nematodes, which is vital in developing effective antiparasitic treatments.

Cite This Article

APA
Janssen IJ, Krücken J, Demeler J, von Samson-Himmelstjerna G. (2015). Transgenically expressed Parascaris P-glycoprotein-11 can modulate ivermectin susceptibility in Caenorhabditis elegans. Int J Parasitol Drugs Drug Resist, 5(2), 44-47. https://doi.org/10.1016/j.ijpddr.2015.03.003

Publication

International journal for parasitology. Drugs and drug resistance
ISSN: 2211-3207
NlmUniqueID: 101576715
Country: Netherlands
Language: English
Volume: 5
Issue: 2
Pages: 44-47

Researcher Affiliations

Janssen, I Jana I
  • Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
Krücken, Jürgen
  • Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
Demeler, Janina
  • Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
von Samson-Himmelstjerna, Georg
  • Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.

MeSH Terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Animals
  • Animals, Genetically Modified
  • Antiparasitic Agents / pharmacology
  • Ascaridoidea / genetics
  • Ascaridoidea / metabolism
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Drug Resistance
  • Gene Expression Regulation
  • Ivermectin / pharmacology

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Citations

This article has been cited 22 times.
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