The nematode (Ascaris suum) intestine is a location of synergistic anthelmintic effects of Cry5B and levamisole Article Swipe
Paul Williams
,
Matthew T. Brewer
,
Raffi V. Aroian
,
Alan P. Robertson
,
Richard J. Martin
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.11.20.567786
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.11.20.567786
A novel group of biocidal compounds are the Crystal 3D (Cry) and Cytolytic (Cyt) proteins produced by Bacillus thuringiensis (Bt). Some Bt Cry proteins have a selective nematocidal activity, with Cry5B being the most studied. Cry5B kills nematode parasites by binding selectively to membrane glycosphingolipids, then forming pores in the cell membranes of the intestine leading to damage. Cry5B selectively targets multiple species of nematodes from different clades and has no effect against mammalian hosts. Levamisole is a cholinomimetic anthelmintic that acts by selectively opening L-subtype nicotinic acetylcholine receptor ion-channels (L-AChRs) that have been found on muscles of nematodes. A synergistic nematocidal interaction between levamisole and Cry5B has been described previously, but the location, mechanism and time-course of this synergism is not known. In this study we follow the timeline of the effects of levamisole and Cry5B on the Ca 2+ levels in enterocyte cells from the intestine of Ascaris suum using fluorescence imaging. The peak Ca 2+ responses to levamisole were observed after approximately 10 minutes while the peak responses to activated Cry5B were observed after approximately 80 minutes. When levamisole and Cry5B were applied simultaneously, we observed that the responses to Cry5B were bigger and occurred sooner than when it was applied by itself. It is proposed that there is an irreversible cytoplasmic Ca 2+ overload that leads to necrotic cell-death in the enterocyte that is induced by levamisole opening Ca 2+ permeable L-subtype nAChRs and the development of Ca 2+ permeable Cry5B toxin pores in enterocyte plasma membranes. The effects of levamisole potentiate and speed the actions of Cry5B.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2023.11.20.567786
- https://www.biorxiv.org/content/biorxiv/early/2023/11/20/2023.11.20.567786.full.pdf
- OA Status
- green
- References
- 50
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4388840065
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4388840065Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2023.11.20.567786Digital Object Identifier
- Title
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The nematode (Ascaris suum) intestine is a location of synergistic anthelmintic effects of Cry5B and levamisoleWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-11-20Full publication date if available
- Authors
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Paul Williams, Matthew T. Brewer, Raffi V. Aroian, Alan P. Robertson, Richard J. MartinList of authors in order
- Landing page
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https://doi.org/10.1101/2023.11.20.567786Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2023/11/20/2023.11.20.567786.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2023/11/20/2023.11.20.567786.full.pdfDirect OA link when available
- Concepts
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Levamisole, Anthelmintic, Ascaris suum, Enterocyte, Biology, Biophysics, Nematode, Chemistry, Cell biology, Biochemistry, Small intestine, Helminths, Immunology, EcologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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50Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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