title: Molecular characterisation of a pH-gated chloride channel from Sarcoptes scabiei.
abstract: Reports of ivermectin resistance in scabies mites raise concerns regarding the sustainability of mass intervention programs for scabies worldwide and for the treatment of crusted scabies. Ligand gated ion channels (LGICs) are the primary targets of ivermectin in invertebrates. We report the molecular characterisation of SsCl--a novel LGIC from Sarcoptes scabiei var. hominis. While SsCl shows sequence similarity to other LGICs, phylogenetic analysis does not suggest strong homology to conventional glutamate, histamine or GABA gated channels. Instead, it is most similar to Drosophila pH-sensitive and group 1 clades. When expressed in Xenopus oocytes, SsCl forms a homomeric, pH-gated chloride channel that is irreversibly activated by ivermectin. These results provide the first confirmation that this group of LGIC exists in arachnids, and suggest that SsCl may be an in vivo target of ivermectin in S. scabiei.
authors.affiliation: Menzies School of Health Research, Institute of Advanced Studies, Charles Darwin University, Darwin, NT, Australia. kate.mounsey@menzies.edu.au
authors.forename: Kate E
authors.initials: KE
authors.lastname: Mounsey
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Dent
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Holt
authors.forename: James
authors.initials: J
authors.lastname: McCarthy
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Currie
authors.forename: Shelley F
authors.initials: SF
authors.lastname: Walton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating; D007559:Ivermectin / Q000494:pharmacology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012520:Sarcoptes scabiei / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
chemical_list: D000977:Antiparasitic Agents; D018118:Chloride Channels; D007559:Ivermectin