Identification and Functional Expression of a Glutamate- and Avermectin-Gated Chloride Channel from , a Southern Hemisphere Sea Louse Affecting Farmed Fish
Sea lice are the main parasites affecting farmed salmon and trout in the world. Caligus rogercresseyi is the principal sea louse species infesting farmed fish in the southern hemisphere. Successful control of these parasites has been achieved using macrocyclic lactones (MLs), but resistance has emerged over time. In other invertebrates, MLs target membrane receptors regulating synaptic transmission in the parasite nervous system. Here we identify and study the function of such a receptor from Caligus rogercresseyi, and gain an idea about how two MLs, ivermectin and emamectin, interact with the receptor to produce their effects. Our molecular modeling of the protein in complex with the drugs suggests a novel way in which ivermectin and emamectin exert their effects on CrGluCl due to a lack of conservation at interaction sites identified in the crystal structure of the receptor from C. elegans. We believe that the identification of a ML target in sea louse will aid the study of drug-resistance mechanisms and could help in the design of new, more efficient antiparasitic drugs.
Vyšlo v časopise:
Identification and Functional Expression of a Glutamate- and Avermectin-Gated Chloride Channel from , a Southern Hemisphere Sea Louse Affecting Farmed Fish. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004402
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004402
Souhrn
Sea lice are the main parasites affecting farmed salmon and trout in the world. Caligus rogercresseyi is the principal sea louse species infesting farmed fish in the southern hemisphere. Successful control of these parasites has been achieved using macrocyclic lactones (MLs), but resistance has emerged over time. In other invertebrates, MLs target membrane receptors regulating synaptic transmission in the parasite nervous system. Here we identify and study the function of such a receptor from Caligus rogercresseyi, and gain an idea about how two MLs, ivermectin and emamectin, interact with the receptor to produce their effects. Our molecular modeling of the protein in complex with the drugs suggests a novel way in which ivermectin and emamectin exert their effects on CrGluCl due to a lack of conservation at interaction sites identified in the crystal structure of the receptor from C. elegans. We believe that the identification of a ML target in sea louse will aid the study of drug-resistance mechanisms and could help in the design of new, more efficient antiparasitic drugs.
Zdroje
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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