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Liu, Y. W.

Publications and source records attributed to Liu, Y. W..

3 recordsLinked to original sources

Spatial Transcriptomics Reveals Region-Specific Host Responses in Amoebic Gill Disease of Atlantic Salmon

Amoebic gill disease (AGD), caused by the parasite Neoparamoeba perurans, is a major welfare and economic burden for the Atlantic salmon aquaculture industry. However, the spatial organisation of immune functions within the gill, the site of infection, remains poorly resolved. Here, we present the first spatial transcriptomic atlas of the Atlantic salmon gill affected by AGD, generated using 10x Genomics Visium on four AGD-positive fish, confirmed by gill scoring and quantitative PCR for parasite load. As no uninfected gills were included, this study maps the anatomical and immunological organisation of AGD-affected gills rather than defining AGD-specific pathology. Unsupervised clustering of spatial gene expression resolved distinct transcriptional domains that grouped into four principal anatomical compartments of the gill, including (i) epithelial and lamellar regions defined by keratin and osmoregulatory gene expression, (ii) gill arch regions enriched for connective tissue and smooth muscle markers, (iii) an erythroid-associated vascular cluster, and (iv) a skeletal muscle cluster with signatures of glycolysis and oxidative phosphorylation. Across these domains, we identified a spatially organised and diffused immune landscape, with pattern recognition receptors, antimicrobial effectors and chemokines concentrated at the filament surface, and immunoglobulin light chain transcripts consistent with B lymphocyte activity enriched toward the gill arch. Integration of the spatial data with a published single-nucleus reference atlas using reference-based deconvolution resolved the cellular identity underlying these domains and revealed frequent co-localisation of immune and structural cell types, suggesting regulated cell to cell communication within the gill-associated lymphoid tissue. Overall, our results show that the Atlantic salmon gill is not a transcriptionally uniform surface but a regionally specialised organ, with immune functions distributed across, and specialised within, distinct anatomical compartments

immunology↗

Repurposing drugs to treat Amoebic Gill Disease in Atlantic Salmon

Neoparameoba perurans causes Amoebic Gill Disease (AGD), a major parasitic disease of marine-phase Atlantic salmon and rainbow trout worldwide. Treatment options are limited to freshwater baths, which are costly at scale and exhibit only limited long-term efficacy. N. perurans contains an obligate eukaryotic symbiont, Perkinsela-like organism (PLO). PLO belongs to the class Kinetoplastida, which includes medically and veterinary important parasites such as Trypanosoma and Leishmania. As such, we hypothesised that trypanocidal drugs developed against other kinetoplastids might also affect N. perurans, potentially through disruption of its PLO symbiont, and used this hypothesis as a rationale for prioritising a focused panel of candidate compounds for screening. A holographic motility-based cytotoxicity assay was established to identify promising candidates in vitro, followed by controlled host tolerance testing and finally a field efficacy sea trial using naturally AGD-exposed site in the west of Ireland. Several compounds showed activity in vitro, especially miltefosine (EC50 1.84 uM, amoebicidal) and isometamidum (EC50 4.63 uM, amoebostatic). In vivo (two intramuscular injections, two weeks apart), miltefosine (Odds Ratio (OR) 0.62), isometamidum (OR 0.61) and benznidazole (OR 0.64) significantly improved gill score over four weeks, with miltefosine showing the largest effect size. Gill parasitaemia, measured via qPCR, was not reduced. Instead, two compounds increased apparent amoeba loads. This work support trypanocidal as potential AGD treatments in the field, although optimisation of dosing, delivery and mode of action requires further study.

microbiology↗

Asymmetric population structure in Neoparamoeba perurans and its kinetoplastid symbiont

Secondary endosymbioses typically involve photosynthetic gain-of-function, at least initially. For Neoparamoeba perurans, the agent of Amoebic Gill Disease in Atlantic salmon, the evolutionary significance of its non-photosynthetic kinetoplastid endosymbiont, Perkinsela, remains a mystery. While such endosymbionts usually mirror organellar uniparental inheritance, departures from strict vertical transmission can significantly impact holobiont evolution and the spread of traits like drug resistance. However, genomic analysis of N. perurans is hampered by continual traffic of bacteria in and out of the amoeba, limiting our understanding of its population dynamics. Here, we developed a dual-target AmpSeq panel from a draft N. perurans genome, enabling simultaneous genotyping of host and symbiont directly from xenic biological samples. Analysis of 58 North Atlantic isolates revealed a striking asymmetry in population structure: the amoeba host forms a diverse, panmictic population with low linkage disequilibrium, whereas Perkinsela exhibits lower diversity and strong clonality. While cophylogenetic analyses confirm a global signal of vertical fidelity, fine-scale genotyping reveals frequent shuffling of host-symbiont pairs. These results suggest that strict host-symbiont co-inheritance is not absolute, perhaps reflecting a system characterised by long-term vertical stability punctuated by intermittent reassortment. Ultimately, we validate AmpSeq as a robust, scalable tool for decoupling complex host-symbiont trajectories and monitoring multi-partner disease dynamics in aquaculture environments.

genomics↗