Evidence for the Induction of Key Components of the NOTCH Signaling Pathway via Deltamethrin and Azamethiphos Treatment in the Sea Louse Caligus rogercresseyi.

Sebastian Boltaña,Cristian Gallardo-Escárate,Jaqueline Chávez-Mardones,Valentina Valenzuela-Muñoz

doi:10.3390/ijms17050304

Abstract

The extensive use of organophosphates and pyrethroids in the aquaculture industry has negatively impacted parasite sensitivity to the delousing effects of these antiparasitics, especially among sea lice species. The NOTCH signaling pathway is a positive regulator of ABC transporter subfamily C expression and plays a key role in the generation and modulation of pesticide resistance. However, little is known about the molecular mechanisms behind pesticide resistance, partly due to the lack of genomic and molecular information on the processes involved in the resistance mechanism of sea lice. Next-generation sequencing technologies provide an opportunity for rapid and cost-effective generation of genome-scale data. The present study, through RNA-seq analysis, determined that the sea louse Caligus rogercresseyi (C. rogercresseyi) specifically responds to the delousing drugs azamethiphos and deltamethrin at the transcriptomic level by differentially activating mRNA of the NOTCH signaling pathway and of ABC genes. These results suggest that frequent antiparasitic application may increase the activity of inhibitory mRNA components, thereby promoting inhibitory NOTCH output and conditions for increased resistance to delousing drugs. Moreover, data analysis underscored that key functions of NOTCH/ABC components were regulated during distinct phases of the drug response, thus indicating resistance modifications in C. rogercresseyi resulting from the frequent use of organophosphates and pyrethroids.

Highlights

Caligus rogercresseyi, like Lepeophtheirus salmonis, is a marine ectoparasite that infests farmed and wild salmonids, causing high economic losses for the industry [1,2]
From the de novo assembly of transcripts obtained from sequencing six developmental stages of C. rogercresseyi [25,26] 15 transcripts participating in the distinct stages of NOTCH pathway signaling were identified, while 27 transcripts were annotated for ATP-binding cassettes (ABC) transporters (Table 1)
RNA-seq analysis showed that components of the NOTCH signaling pathway modulated by AZA presented differences in expression compared to the control group

Summary

Introduction

Like Lepeophtheirus salmonis, is a marine ectoparasite that infests farmed and wild salmonids, causing high economic losses for the industry [1,2]. ATP-driven efflux transport systems have been linked with resistance to pesticides and other drugs [7,8,9,10]. There are few studies on the NOTCH and ABC interactome in marine ectoparasites treated with delousing drugs, and insight on this subject could provide important information regarding the generation and modulation of pesticide resistance. NOTCH is a heterodimeric Type 1 transmembrane receptor coded by one of four NOTCH genes (Noctch1–NOTCH4) [11] Interaction with these receptors activates γ-secretase and the A Disintegrin and Metalloprotease complexes, resulting in the cleavage of the intracellular C-terminal fragment of NOTCH (NIC). The CSL/NIC activation complex trans-activates various target genes, including genes from HES/HEY family members that actively repress a tissue-specific NOTCH-signaling pathway. NIC participation has been reported in resistance to adriamycin, cisplatin, etoposide, and taxol in MCF7 cells, MOLT4 cells, breast adenocarcinoma cell lines, and infantile lymphoma T-cells, respectively [15]

Methods

Results

Discussion

Conclusion