RRC ID 80945
Author Brinzer RA, Winter AD, Page AP.
Title The relationship between intraflagellar transport and upstream protein trafficking pathways and macrocyclic lactone resistance in Caenorhabditis elegans.
Journal G3 (Bethesda)
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 toward macrocyclic lactones such as ivermectin (an avermectin) and moxidectin (a milbemycin) either through reduced uptake or intertissue signaling 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 nonmotile 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 that are directly involved in amphid, cilia, and intraflagellar transport function.
Volume 14(3)
Published 2024-3-6
DOI 10.1093/g3journal/jkae009
PII 7559253
PMID 38227795
PMC PMC10917524
MeSH Animals Anthelmintics* / metabolism Anthelmintics* / pharmacology Anthelmintics* / therapeutic use Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Humans Lactones* / pharmacology Protein Transport
C.elegans tm10737 tm604 tm1745 tm5255 tm3067 tm925 tm1416 tm8137 tm3304