Two novel loci underlie natural differences in Caenorhabditis elegans abamectin responses.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
11
01
2021
accepted:
02
03
2021
revised:
25
03
2021
pubmed:
16
3
2021
medline:
23
7
2021
entrez:
15
3
2021
Statut:
epublish
Résumé
Parasitic nematodes cause a massive worldwide burden on human health along with a loss of livestock and agriculture productivity. Anthelmintics have been widely successful in treating parasitic nematodes. However, resistance is increasing, and little is known about the molecular and genetic causes of resistance for most of these drugs. The free-living roundworm Caenorhabditis elegans provides a tractable model to identify genes that underlie resistance. Unlike parasitic nematodes, C. elegans is easy to maintain in the laboratory, has a complete and well annotated genome, and has many genetic tools. Using a combination of wild isolates and a panel of recombinant inbred lines constructed from crosses of two genetically and phenotypically divergent strains, we identified three genomic regions on chromosome V that underlie natural differences in response to the macrocyclic lactone (ML) abamectin. One locus was identified previously and encodes an alpha subunit of a glutamate-gated chloride channel (glc-1). Here, we validate and narrow two novel loci using near-isogenic lines. Additionally, we generate a list of prioritized candidate genes identified in C. elegans and in the parasite Haemonchus contortus by comparison of ML resistance loci. These genes could represent previously unidentified resistance genes shared across nematode species and should be evaluated in the future. Our work highlights the advantages of using C. elegans as a model to better understand ML resistance in parasitic nematodes.
Identifiants
pubmed: 33720993
doi: 10.1371/journal.ppat.1009297
pii: PPATHOGENS-D-21-00076
pmc: PMC7993787
doi:
Substances chimiques
Anthelmintics
0
Chloride Channels
0
glutamate-gated chloride channels
0
abamectin
5U8924T11H
Ivermectin
70288-86-7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009297Subventions
Organisme : NIAID NIH HHS
ID : R01 AI153088
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI121836
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008061
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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