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Cyclotide interactions with the nematode external surface.

Michelle L Colgrave1, Yen-Hua Huang, David J Craik

  • 1University of Queensland Institute for Molecular Bioscience, Brisbane, Australia.

Antimicrobial Agents and Chemotherapy
|March 10, 2010
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Summary
This summary is machine-generated.

Cyclotides, cyclic plant peptides, are toxic to gastrointestinal nematodes like Haemonchus contortus by increasing membrane permeability. This surface interaction, not ingestion, causes toxicity in both larval and adult worms.

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Area of Science:

  • Biochemistry
  • Parasitology
  • Molecular Biology

Background:

  • Cyclotides are cyclic peptides with a cystine knot structure found in plants.
  • They exhibit anthelminthic activity against important sheep gastrointestinal nematodes, Haemonchus contortus and Trichostrongylus colubriformis.
  • The precise mechanism of cyclotide action against nematodes is not fully understood.

Purpose of the Study:

  • To investigate the interaction of the cyclotide kalata B1 with the external surface of Haemonchus contortus.
  • To determine if cyclotide toxicity requires ingestion or if surface interaction alone is sufficient.
  • To elucidate the mechanism by which cyclotides exert their toxic effects on nematodes.

Main Methods:

  • Studied the toxicity of kalata B1 on H. contortus adult worms with pharyngeal ligatures.
  • Assessed cyclotide toxicity on nonfeeding larval stages.
  • Measured tritiated inulin uptake in ligated adult worms.
  • Utilized polyethylene glycols of various sizes in toxicity and hemolytic assays.

Main Results:

  • Cyclotides are toxic to H. contortus regardless of ingestion, indicating surface interaction is sufficient.
  • Kalata B1 increased the permeability of the external membranes of adult nematodes.
  • Polyethylene glycols protected larval stages and inhibited cyclotide-induced hemolysis, suggesting pore formation.
  • Cyclotides likely interact with the lipid-rich epicuticle layer of the nematode surface.

Conclusions:

  • Cyclotides exert their anthelminthic effects through direct interaction with the nematode's external surface, primarily the epicuticle.
  • The mechanism involves the formation of pores in the nematode's outer membranes, leading to increased permeability and toxicity.
  • This surface-mediated toxicity is effective against both larval and adult stages of H. contortus.