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Polymorphism-driven transcriptomic changes in anthelmintic metabolism pathways of Anisakis simplex s.s. L3 larvae
Mateusz Maździarz1, Iwona Polak2, Lukasz Paukszto1
1Department of Botany and Evolutionary Ecology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, Plac Łódzki 1, 10-721, Olsztyn, Poland.
Parasites & Vectors
|December 19, 2025
Summary
This study reveals how Anisakis simplex parasites develop resistance to anthelmintics through distinct genetic changes. Understanding these drug-specific molecular mechanisms is key for developing new treatments against helminth infections.
Area of Science:
- Parasitology
- Molecular Biology
- Genomics
Background:
- Helminth infections pose significant challenges in human and veterinary medicine.
- Anthelmintic resistance is an emerging complication in treating these infections.
- Anisakis simplex, a zoonotic nematode, is of growing concern due to its allergenic potential and clinical relevance, yet its molecular response to anthelmintics is poorly understood.
Purpose of the Study:
- To investigate the molecular mechanisms of Anisakis simplex response to anthelmintic treatment.
- To identify drug-specific transcriptomic and genetic variations associated with anthelmintic exposure.
Main Methods:
- Third-stage larvae (L3) of Anisakis simplex were exposed to albendazole (ALB), ivermectin (IVC), and pyrantel (PYR).
- High-throughput RNA sequencing, differential gene expression analysis, multivariate alternative splicing analysis (rMATS), and single nucleotide variant (SNV) profiling via Oxford Nanopore sequencing were employed.
- Effects were assessed across protein-coding genes, long non-coding RNAs (lncRNAs), and splicing events.
Main Results:
- Albendazole (ALB) primarily altered the expression of cuticle-associated genes.
- Ivermectin (IVC) induced extensive alternative splicing in immune-related pathways, including moesin/ezrin/radixin-like protein 1.
- Pyrantel (PYR) exposure was linked to widespread SNVs in neuronal and metabolic genes, notably disrupting trehalose metabolism via trehalose phosphatase.
- Allelic variations were identified in 68 (ALB), 83 (PYR), and 95 (IVC) protein-coding genes, including those involved in detoxification, oxidative stress, and cytoskeletal remodeling.
Conclusions:
- Anisakis simplex exhibits complex, drug-specific regulatory responses to anthelmintics, involving transcriptional remodeling, alternative splicing, and functional SNVs.
- Novel modulation of trehalose metabolism and cytoskeletal genes, along with potential roles for ABC transporters and RNA-binding proteins, suggests diverse adaptive strategies for anthelmintic tolerance.
- This integrated analysis provides novel insights into molecular resistance mechanisms in marine nematodes, informing therapeutic innovation and monitoring strategies.
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