Genome‐Wide Protein Interaction Analysis in Parasitic Gyrodactylus Flatworms–Fish Hosts System and Drug Target Identification

The host-parasite arms race involves complex molecular crosstalk mediated by protein-protein interactions (PPIs). Bioinformatic analyses can be used to predict both host-parasite PPIs and potential drug targets in parasite genomes, but high-quality genomic data remain scarce for parasitic monogenean flatworms. Herein, an experimental lineage of Gyrodactylus kobayashii (Monopisthocotylea: Gyrodactylidae) is set up on goldfish hosts and used to conduct phased genome assembly using long-range PacBio HiFi and Hi-C technologies. In silico analyses of genomes of three Gyrodactylus species identified innexins as the most promising novel drug candidate genes. Drug screening and experimental verification singled out Imatinib as the most promising drug targeting innexins, with a high efficiency against G. kobayashii (100% mortality at 25 µM within 6 h in vitro) and low toxicity to the host. Prediction of PPIs in three Gyrodactylus-host pairs revealed proteins associated with cAMP-dependent signaling as key candidates, including the host's PRKACB and the parasite's PRKAR2A, RAP1A, ULK2, and Catenin Beta-2. Two interacting G proteins are also identified: GNAO1 and GNB5. As the first high-quality phased chromosome-level genomic assembly for "monogeneans" and the first identification of PPIs in a fish-parasite system, this study significantly advances the understanding of host-parasite interactions at the genomic level.

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Publication Details

Journal
Advanced Science
Published
2025-09-29
DOI
https://doi.org/10.1002/advs.202514618
Primary Topic
Parasite Biology and Host Interactions
Type
article
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article

Genome‐Wide Protein Interaction Analysis in Parasitic Gyrodactylus Flatworms–Fish Hosts System and Drug Target Identification

Hong‐Peng Lei, Chuan‐Yu Xiang, Feng Zhang, Ivan Jakovlić et al.
Advanced Science
Parasite Biology and Host Interactions
article

Genome‐Wide Protein Interaction Analysis in Parasitic Gyrodactylus Flatworms–Fish Hosts System and Drug Target Identification

Hong‐Peng Lei, Chuan‐Yu Xiang, Feng Zhang, Ivan Jakovlić, Xiaofei Zeng, Gui‐Tang Wang, Ye Hu, Benhe Zeng, Dong Zhang, Fei Liu, Jinsong Chen, Wenxiang Li, Jinliang Zhao, Rui Song, Shun Zhou, Yiwen Ma, Yuying Shi
article en

Abstract

The host-parasite arms race involves complex molecular crosstalk mediated by protein-protein interactions (PPIs). Bioinformatic analyses can be used to predict both host-parasite PPIs and potential drug targets in parasite genomes, but high-quality genomic data remain scarce for parasitic monogenean flatworms. Herein, an experimental lineage of Gyrodactylus kobayashii (Monopisthocotylea: Gyrodactylidae) is set up on goldfish hosts and used to conduct phased genome assembly using long-range PacBio HiFi and Hi-C technologies. In silico analyses of genomes of three Gyrodactylus species identified innexins as the most promising novel drug candidate genes. Drug screening and experimental verification singled out Imatinib as the most promising drug targeting innexins, with a high efficiency against G. kobayashii (100% mortality at 25 µM within 6 h in vitro) and low toxicity to the host. Prediction of PPIs in three Gyrodactylus-host pairs revealed proteins associated with cAMP-dependent signaling as key candidates, including the host's PRKACB and the parasite's PRKAR2A, RAP1A, ULK2, and Catenin Beta-2. Two interacting G proteins are also identified: GNAO1 and GNB5. As the first high-quality phased chromosome-level genomic assembly for "monogeneans" and the first identification of PPIs in a fish-parasite system, this study significantly advances the understanding of host-parasite interactions at the genomic level.

Advanced ScienceVol. 12(45)
Gansu Agricultural University (CN), Chinese Academy of Sciences (CN), Shenyang Science and Technology Bureau (CN), Agricultural Genomics Institute at Shenzhen (CN), Institute of Hydrobiology (CN), Hunan Agricultural Products (China) (CN), Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (CN), Shenyang Environmental Protection Bureau (CN), Tibet Academy of Agricultural and Animal Husbandry Sciences (CN), Institute of Tibetan Plateau Research (CN), Chinese Academy of Fishery Sciences (CN), Lanzhou University (CN)
Openalex Percentile: Top 74%
Parasite Biology and Host Interactions
DOIOpen Access PDFOpenAlex
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