Brinzer, R. A. , Winter, A. D. and Page, A. P. (2024) The relationship between Intra-Flagellar Transport and upstream protein trafficking pathways and macrocyclic lactone resistance in Caenorhabditis elegans. G3: Genes, Genomes, Genetics, 14(3), jkae009. (doi: 10.1093/g3journal/jkae009) (PMID:38227795)
![[img]](https://eprints.gla.ac.uk/style/images/fileicons/text.png) |
Text
316376.pdf - Published Version Available under License Creative Commons Attribution. 1MB |
Abstract
Parasitic nematodes are globally important and place a heavy disease burden on infected humans, crops and livestock, while commonly administered anthelmintics used for treatment are being rendered ineffective by increasing levels of resistance. It has recently been shown in the model nematode Caenorhabditis elegans that the sensory cilia of the amphid neurons play an important role in resistance towards macrocyclic lactones such as ivermectin (an avermectin) and moxidectin (a milbemycin) either through reduced uptake or inter-tissue signalling pathways. This study interrogated the extent to which ciliary defects relate to macrocyclic lactone resistance and dye filling defects using a combination of forward genetics and targeted resistance screening approaches and confirmed the importance of intraflagellar transport in this process. This approach also identified the protein trafficking pathways used by the downstream effectors and the components of the ciliary basal body that are required for effector entry into these non-motile structures. In total 24 novel C. elegans anthelmintic survival associated genes were identified in this study. When combined with previously known resistance genes, there are now 46 resistance associated genes which are directly involved in amphid, cilia and IFT function.
| Item Type: | Articles |
|---|---|
| Additional Information: | This study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) grant No. BB/R00711X/1. |
| Keywords: | Caenorhabditis elegans, Macrocyclic lactone, Ivermectin, Moxidectin, Anthelmintic resistance, 13 Xenobiotic resistance, Amphids, Ciliogenesis, Intraflagellar transport. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Page, Professor Tony and Brinzer, Dr Robert and Winter, Dr Alan |
| Authors: | Brinzer, R. A., Winter, A. D., and Page, A. P. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | G3: Genes, Genomes, Genetics |
| Publisher: | Genetics Society of America |
| ISSN: | 2160-1836 |
| ISSN (Online): | 2160-1836 |
| Published Online: | 16 January 2024 |
| Copyright Holders: | Copyright © The Author(s) 2024 |
| First Published: | First published in G3: Genes, Genomes, Genetics 14(3):jkae009 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information