Cargando…

Anthelmintic resistance and homeostatic plasticity (Brugia malayi)

Homeostatic plasticity refers to the capacity of excitable cells to regulate their activity to make compensatory adjustments to long-lasting stimulation. It is found across the spectrum of vertebrate and invertebrate species and is driven by changes in cytosolic calcium; it has not been explored in...

Descripción completa

Detalles Bibliográficos
Autores principales: Kashyap, Sudhanva S., Verma, Saurabh, McHugh, Mark, Wolday, Mengisteab, Williams, Paul D., Robertson, Alan P., Martin, Richard J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280109/
https://www.ncbi.nlm.nih.gov/pubmed/34262123
http://dx.doi.org/10.1038/s41598-021-93911-4
_version_ 1783722583138500608
author Kashyap, Sudhanva S.
Verma, Saurabh
McHugh, Mark
Wolday, Mengisteab
Williams, Paul D.
Robertson, Alan P.
Martin, Richard J.
author_facet Kashyap, Sudhanva S.
Verma, Saurabh
McHugh, Mark
Wolday, Mengisteab
Williams, Paul D.
Robertson, Alan P.
Martin, Richard J.
author_sort Kashyap, Sudhanva S.
collection PubMed
description Homeostatic plasticity refers to the capacity of excitable cells to regulate their activity to make compensatory adjustments to long-lasting stimulation. It is found across the spectrum of vertebrate and invertebrate species and is driven by changes in cytosolic calcium; it has not been explored in parasitic nematodes when treated with therapeutic drugs. Here we have studied the adaptation of Brugia malayi to exposure to the anthelmintic, levamisole that activates muscle AChR ion-channels. We found three phases of the Brugia malayi motility responses as they adapted to levamisole: an initial spastic paralysis; a flaccid paralysis that follows; and finally, a recovery of motility with loss of sensitivity to levamisole at 4 h. Motility, calcium-imaging, patch-clamp and molecular experiments showed the muscle AChRs are dynamic with mechanisms that adjust their subtype composition and sensitivity to levamisole. This homeostatic plasticity allows the parasite to adapt resisting the anthelmintic.
format Online
Article
Text
id pubmed-8280109
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-82801092021-07-15 Anthelmintic resistance and homeostatic plasticity (Brugia malayi) Kashyap, Sudhanva S. Verma, Saurabh McHugh, Mark Wolday, Mengisteab Williams, Paul D. Robertson, Alan P. Martin, Richard J. Sci Rep Article Homeostatic plasticity refers to the capacity of excitable cells to regulate their activity to make compensatory adjustments to long-lasting stimulation. It is found across the spectrum of vertebrate and invertebrate species and is driven by changes in cytosolic calcium; it has not been explored in parasitic nematodes when treated with therapeutic drugs. Here we have studied the adaptation of Brugia malayi to exposure to the anthelmintic, levamisole that activates muscle AChR ion-channels. We found three phases of the Brugia malayi motility responses as they adapted to levamisole: an initial spastic paralysis; a flaccid paralysis that follows; and finally, a recovery of motility with loss of sensitivity to levamisole at 4 h. Motility, calcium-imaging, patch-clamp and molecular experiments showed the muscle AChRs are dynamic with mechanisms that adjust their subtype composition and sensitivity to levamisole. This homeostatic plasticity allows the parasite to adapt resisting the anthelmintic. Nature Publishing Group UK 2021-07-14 /pmc/articles/PMC8280109/ /pubmed/34262123 http://dx.doi.org/10.1038/s41598-021-93911-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kashyap, Sudhanva S.
Verma, Saurabh
McHugh, Mark
Wolday, Mengisteab
Williams, Paul D.
Robertson, Alan P.
Martin, Richard J.
Anthelmintic resistance and homeostatic plasticity (Brugia malayi)
title Anthelmintic resistance and homeostatic plasticity (Brugia malayi)
title_full Anthelmintic resistance and homeostatic plasticity (Brugia malayi)
title_fullStr Anthelmintic resistance and homeostatic plasticity (Brugia malayi)
title_full_unstemmed Anthelmintic resistance and homeostatic plasticity (Brugia malayi)
title_short Anthelmintic resistance and homeostatic plasticity (Brugia malayi)
title_sort anthelmintic resistance and homeostatic plasticity (brugia malayi)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280109/
https://www.ncbi.nlm.nih.gov/pubmed/34262123
http://dx.doi.org/10.1038/s41598-021-93911-4
work_keys_str_mv AT kashyapsudhanvas anthelminticresistanceandhomeostaticplasticitybrugiamalayi
AT vermasaurabh anthelminticresistanceandhomeostaticplasticitybrugiamalayi
AT mchughmark anthelminticresistanceandhomeostaticplasticitybrugiamalayi
AT woldaymengisteab anthelminticresistanceandhomeostaticplasticitybrugiamalayi
AT williamspauld anthelminticresistanceandhomeostaticplasticitybrugiamalayi
AT robertsonalanp anthelminticresistanceandhomeostaticplasticitybrugiamalayi
AT martinrichardj anthelminticresistanceandhomeostaticplasticitybrugiamalayi