Loading…

A new class of natural anthelmintics targeting lipid metabolism

Parasitic helminths are a major global health threat, infecting nearly one-fifth of the human population and causing significant losses in livestock and crops. Resistance to the few anthelmintic drugs is increasing. Here, we report a set of avocado fatty alcohols/acetates (AFAs) that exhibit nematoc...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2025-01, Vol.16 (1), p.305-15, Article 305
Main Authors: Fahs, Hala Zahreddine, Refai, Fathima S., Gopinadhan, Suma, Moussa, Yasmine, Gan, Hin Hark, Hunashal, Yamanappa, Battaglia, Gennaro, Cipriani, Patricia G., Ciancia, Claire, Rahiman, Nabil, Kremb, Stephan, Xie, Xin, Pearson, Yanthe E., Butterfoss, Glenn L., Maizels, Rick M., Esposito, Gennaro, Page, Antony P., Gunsalus, Kristin C., Piano, Fabio
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Parasitic helminths are a major global health threat, infecting nearly one-fifth of the human population and causing significant losses in livestock and crops. Resistance to the few anthelmintic drugs is increasing. Here, we report a set of avocado fatty alcohols/acetates (AFAs) that exhibit nematocidal activity against four veterinary parasitic nematode species: Brugia pahangi , Teladorsagia circumcincta and Heligmosomoides polygyrus , as well as a multidrug resistant strain (UGA) of Haemonchus contortus . AFA shows significant efficacy in H. polygyrus infected mice. In C. elegans , AFA exposure affects all developmental stages, causing paralysis, impaired mitochondrial respiration, increased reactive oxygen species production and mitochondrial damage. In embryos, AFAs penetrate the eggshell and induce rapid developmental arrest. Genetic and biochemical tests reveal that AFAs inhibit POD-2, encoding an acetyl CoA carboxylase, the rate-limiting enzyme in lipid biosynthesis. These results uncover a new anthelmintic class affecting lipid metabolism. Avocado fatty alcohols/acetates (AFAs) are effective against parasitic nematodes, including drug resistant strains, and show safety in mammalian cells. AFAs target lipid metabolism, offering the potential for new anthelmintic treatment pathways.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-54965-w