Gene co-expression network analysis reveal core responsive genes in Parascaris univalens tissues following ivermectin exposure.
Authors: Dube Faruk, Delhomme Nicolas, Martin Frida, Hinas Andrea, Åbrink Magnus, Svärd Staffan, Tydén Eva
Journal: PloS one
Summary
# Editorial Summary Understanding how *Parascaris univalens* responds to ivermectin at the molecular level is increasingly important as anthelmintic resistance threatens treatment efficacy in equine practice. Researchers used gene co-expression network analysis on RNA-sequencing data from adult worms exposed to two ivermectin concentrations (10⁻¹¹ M and 10⁻⁹ M) for 24 hours, examining transcriptional changes separately in the anterior end and intestinal tissue. The intestine demonstrated substantially greater ivermectin-induced activity than the anterior end, with 219 core genes identified across seven co-expression modules; at the lower concentration, intestinal genes showed suppression of cell cycle and ribosomal function, whilst at the higher concentration, genes involved in cuticle and membrane integrity were upregulated. Particularly intriguing was the calcium-signalling gene *gegf-1*, which bridged 71 genes across multiple modules and may regulate transmembrane signalling pathways critical to drug uptake. These tissue-specific and dose-dependent expression patterns suggest *P. univalens* employs selective mechanisms to manage ivermectin exposure, potentially informing both targeted functional studies of resistance mechanisms and future strategies for combating anthelmintic resistance in equine populations.
Read the full abstract on PubMed
Practical Takeaways
- •Ivermectin resistance in equine roundworms involves tissue-specific mechanisms, particularly in intestinal tissue; understanding these mechanisms may help develop new treatment strategies
- •The dose-dependent gene expression patterns and alternative drug uptake pathways identified suggest that alternative anthelmintics or combination therapies may be warranted in resistant populations
- •Future parasite control programs should consider that resistance involves complex transcriptional regulation rather than single-gene mechanisms, informing strategic rotation and selection of anthelmintics
Key Findings
- •Intestinal tissue showed substantially greater ivermectin-induced transcriptional activity compared to anterior end tissue
- •Gene co-expression network analysis identified 219 core genes responsive to ivermectin, predominantly expressed in intestinal tissue
- •Three genes (sorb-1, gmap-1, col-37/col-102) showed dose-dependent switching from downregulation at 10⁻¹¹ M to upregulation at 10⁻⁹ M ivermectin
- •Calcium-signaling gene gegf-1 uniquely connected 71 genes across four modules, suggesting a key regulatory role in ivermectin response