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.

Trypsin Genes Are Regulated through the miRNA Bantam and Associated with Drug Sensitivity in the Sea Louse Caligus rogercresseyi

“…However, these markers have not been described yet in resistant populations for this species. Another strategy in C. rogercresseyi is to identify several genes and pathways related to drug response through next-generation sequencing and RNA-seq analyses [11]. Thus, the characterization of resistant genotypes has been enhanced by describing molecular functions that were not evaluated at first for assessing pharmacological resistance in the sea louse.…”

“…Thus, the characterization of resistant genotypes has been enhanced by describing molecular functions that were not evaluated at first for assessing pharmacological resistance in the sea louse. Transcriptome analyses have also allowed the description of novel non-coding RNAs (long non-coding RNAs and miRNAs) associated with delousing drug response in C. rogercresseyi, expanding the knowledge to other overlooked genomic regions [11,28]. Nonetheless, the characterization of the complete genome of C. rogercresseyi at the chromosome scale [31] could reshape the understanding of pharmacological resistance and delousing drugs in this species.…”

“…However, the control by the use of these molecules has been threatened by the emergence of pharmacological resistance in Lepeophtheirus salmonis [8] and the reduced efficacy reported in C. rogercresseyi [9,10]. This evidence is supported by the identification of putative drug detoxification systems and excretion mechanisms found in sea lice species [11].…”

“…In sea lice species, mutations in target genes for delousing drugs have been associated with resistant genotypes in L. salmonis widely distributed among the Northern Hemisphere coasts [15,16]. However, recent studies applying next-generation sequencing techniques have described diverse and complex molecular responses that suggest novel pharmacological resistance mechanisms in the sea louse C. rogercresseyi [11,17,18]. Among these genes, trypsins are a group of genes involved in drug detoxification and differentially expressed in C. rogercresseyi exposed to azamethiphos and deltamethrin drugs [19].…”

“…In addition, two isoforms of trypsin genes showed strong transcriptional differences between susceptible and resistant lice strains to the pesticide deltamethrin. Notably, findings have suggested putative molecular interactions with non-coding genes [11].…”