Dataset Information

Tackling the Molecular Drug Sensitivity in the Sea Louse Caligus rogercresseyi Based on mRNA and lncRNA Interactions.

ABSTRACT: Caligus rogercresseyi, commonly known as sea louse, is an ectoparasite copepod that impacts the salmon aquaculture in Chile, causing losses of hundreds of million dollars per year. This pathogen is mainly controlled by immersion baths with delousing drugs, which can lead to resistant traits selection in lice populations. Bioassays are commonly used to assess louse drug sensitivity, but the current procedures may mask relevant molecular responses. This study aimed to discover novel coding genes and non-coding RNAs that could evidence drug sensitivity at the genomic level. Sea lice samples from populations with contrasting sensitivity to delousing drugs were collected. Bioassays using azamethiphos, cypermethrin, and deltamethrin drugs were conducted to evaluate the sensitivity and to collect samples for RNA-sequencing. Transcriptome sequencing was conducted on samples exposed to each drug to evaluate the presence of coding and non-coding RNAs associated with the response of these compounds. The results revealed specific transcriptome patterns in lice exposed to azamethiphos, deltamethrin, and cypermethrin drugs. Enrichment analyses of Gene Ontology terms showed specific biological processes and molecular functions associated with each delousing drug analyzed. Furthermore, novel long non-coding RNAs (lncRNAs) were identified in C. rogercresseyi and tightly linked to differentially expressed coding genes. A significant correlation between gene transcription patterns and phenotypic effects was found in lice collected from different salmon farms with contrasting drug treatment efficacies. The significant correlation among gene transcription patterns with the historical background of drug sensitivity suggests novel molecular mechanisms of pharmacological resistance in lice populations.

SUBMITTER: Nunez-Acuna G

PROVIDER: S-EPMC7464394 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Tackling the Molecular Drug Sensitivity in the Sea Louse <i>Caligus rogercresseyi</i> Based on mRNA and lncRNA Interactions.

Núñez-Acuña Gustavo G Sáez-Vera Constanza C Valenzuela-Muñoz Valentina V Valenzuela-Miranda Diego D Arriagada Gabriel G Gallardo-Escárate Cristian C

Genes 20200727 8

<i>Caligus rogercresseyi</i>, commonly known as sea louse, is an ectoparasite copepod that impacts the salmon aquaculture in Chile, causing losses of hundreds of million dollars per year. This pathogen is mainly controlled by immersion baths with delousing drugs, which can lead to resistant traits selection in lice populations. Bioassays are commonly used to assess louse drug sensitivity, but the current procedures may mask relevant molecular responses. This study aimed to discover novel coding ...[more]

PMID: 32726954

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Project description:Parasitic sea lice represent a major sanitary threat to marine salmonid aquaculture, an industry accounting for 7% of world fish production. Caligus rogercresseyi is the principal sea louse species infesting farmed salmon and trout in the southern hemisphere. Most effective control of Caligus has been obtained with macrocyclic lactones (MLs) ivermectin and emamectin. These drugs target glutamate-gated chloride channels (GluCl) and act as irreversible non-competitive agonists causing neuronal inhibition, paralysis and death of the parasite. Here we report the cloning of a full-length CrGluCl? receptor from Caligus rogercresseyi. Expression in Xenopus oocytes and electrophysiological assays show that CrGluCl? is activated by glutamate and mediates chloride currents blocked by the ligand-gated anion channel inhibitor picrotoxin. Both ivermectin and emamectin activate CrGluCl? in the absence of glutamate. The effects are irreversible and occur with an EC(50) value of around 200 nM, being cooperative (n(H)?=?2) for ivermectin but not for emamectin. Using the three-dimensional structure of a GluCl? from Caenorabditis elegans, the only available for any eukaryotic ligand-gated anion channel, we have constructed a homology model for CrGluCl?. Docking and molecular dynamics calculations reveal the way in which ivermectin and emamectin interact with CrGluCl?. Both drugs intercalate between transmembrane domains M1 and M3 of neighbouring subunits of a pentameric structure. The structure displays three H-bonds involved in this interaction, but despite similarity in structure only of two these are conserved from the C. elegans crystal binding site. Our data strongly suggest that CrGluCl? is an important target for avermectins used in the treatment of sea louse infestation in farmed salmonids and open the way for ascertaining a possible mechanism of increasing resistance to MLs in aquaculture industry. Molecular modeling could help in the design of new, more efficient drugs whilst functional expression of the receptor allows a first stage of testing of their efficacy.

Dataset Information

Tackling the Molecular Drug Sensitivity in the Sea Louse Caligus rogercresseyi Based on mRNA and lncRNA Interactions.

Publications

Tackling the Molecular Drug Sensitivity in the Sea Louse <i>Caligus rogercresseyi</i> Based on mRNA and lncRNA Interactions.

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