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
|
Resource |
C.elegans |
tm10737
tm604
tm1745
tm5255
tm3067
tm925
tm1416
tm8137
tm3304 |