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Molecular characterisation of a pH-gated chloride channel from Sarcoptes scabiei

  • Original Paper
  • Published:
Invertebrate Neuroscience

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.

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References

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    PubMed  CAS  Google Scholar 

  • Blackhall WJ, Pouliot JF, Prichard RK, Beech RN (1998) Haemonchus contortus: Selection at a glutamate gated chloride channel gene in ivermectin and moxidectin selected strains. Exp Parasitol 90:42–48

    Article  PubMed  CAS  Google Scholar 

  • Blackhall WJ, Prichard RK, Beech RN (2003) Selection at a GABA receptor gene in Haemonchus contortus resistant to avermectins/milbemycins. Mol Biochem Parasitol 131:137–145

    Article  PubMed  CAS  Google Scholar 

  • Bloomquist JR (2003) Chloride channels as tools for developing selective insecticides. Arch Insect Biochem Physiol 54:145–156

    Article  PubMed  CAS  Google Scholar 

  • Cary RB, Klymkowsky MW, Evans RM, Domingo A, Dent JA, Backhus LE (1994) Vimentin’s tail interacts with actin-containing structures in vivo. J Cell Sci 107:1609–1622

    PubMed  CAS  Google Scholar 

  • Cully DF, Paress PS, Liu KK, Schaeffer JM, Arena JP (1996) Identification of a Drosophila melanogaster gluatmate-gated chloride channel sensitive to the antiparasitic agent avermectin. J Biol Chem 271:20187–20191

    Article  PubMed  CAS  Google Scholar 

  • Cully DF, Vassilatis DK, Liu KK, Paress PS, Van der Ploeg LHT, Schaeffer JM, Arena JP (1994) Cloning of an avermectin sensitive glutamate gated chloride channel from Caenorhabditis elegans. Nature 371:707–711

    Article  PubMed  CAS  Google Scholar 

  • Currie BJ, Harumal P, McKinnon M, Walton SF (2004) First documentation of in vivo and in vitro ivermectin resistance in Sarcoptes scabiei. Clin Infect Dis 39:e8–12

    Article  PubMed  CAS  Google Scholar 

  • Dent JA (2006) Evidence for a diverse cys-loop ligand-gated ion channel superfamily in early bilateria. J Mol Evol 62:523–535

    Article  PubMed  CAS  Google Scholar 

  • Dent JA, Smith MM, Vassilatis DK, Avery L (2000) The genetics of ivermectin resistance in Caenorhabditis elegans. Proc Natl Acad Sci USA 97:2674–2679

    Article  PubMed  CAS  Google Scholar 

  • Felsenstein J (1989) PHYLIP—Phylogeny Inference Package (Version 3.2). Cladistics 5:164–166

    Google Scholar 

  • Feng XP, Hayashi J, Beech RN, Prichard RK (2002) Study of the nematode putative GABA type-A receptor subunits: evidence for modulation by ivermectin. J Neurochem 83:870–888

    Article  PubMed  CAS  Google Scholar 

  • Ffrench-Constant RH, Mortlock DP, Shaffer CD, MacIntyre RJ, Roush RT (1991) Molecular cloning and transformation of cyclodiene resistance in Drosophila: an invertebrate gamma-aminobutyric acid subtype A receptor locus. Proc Natl Acad Sci USA 88:7209–7213

    Article  PubMed  CAS  Google Scholar 

  • Fischer K, Holt DC, Harumal P, Currie BJ, Walton SF, Kemp DJ (2003a) Generation and characterization of cDNA clones from Sarcoptes scabiei var. hominis for an expressed sequence tag library: identification of homologues of house dust mite allergens. Am J Trop Med Hyg 68:61–64

    PubMed  CAS  Google Scholar 

  • Fischer K, Holt DC, Wilson P, Davis J, Hewitt V, Johnson M, McGrath A, Currie BJ, Walton SF, Kemp DJ (2003b) Normalization of a cDNA library cloned in lambda ZAP by a long PCR and cDNA reassociation procedure. Biotechniques 34:250–252, 254

    PubMed  CAS  Google Scholar 

  • Galzi JL, Devillers-Thiery A, Hussy N, Bertrand S, Changeux JP, Bertrand D (1992) Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic. Nature 359:500–505

    Article  PubMed  CAS  Google Scholar 

  • Georgiev PG, Wolstenholme AJ, Pak WL, Semenov EP (2002) Differential responses to avermectins in ort mutants of Drosophila melanogaster. Pestic Biochem Physiol 72:65–71

    Article  CAS  Google Scholar 

  • Gisselmann G, Pusch H, Hovemann B, Hatt H (2002) Two cDNAs encoding for histamine-gated ion channels in D. melanogaster. Nat Neurosci 5:11–12

    Article  PubMed  CAS  Google Scholar 

  • Goldin AL (1992) Maintenence of Xenopus laevius and Oocyte Injection. Methods Enzymol 207:266–279

    Article  PubMed  CAS  Google Scholar 

  • Hofmann K, Stoffel W (1993) TMbase—A database of membrane spanning proteins segments. J Biol Chem 374:166

    Google Scholar 

  • Holden-Dye L, Walker RJ (1990) Avermectin and avermectin derivatives are antagonists at the γ-aminobutyric acid (GABA) receptor on the somatic muscle cells of Ascaris; is this the site of anthelmintic action? Parasitology 101 Pt 2:265–271

    Article  PubMed  CAS  Google Scholar 

  • Holt DC, Fischer K, Allen GE, Wilson D, Wilson P, Slade R, Currie BJ, Walton SF, Kemp DJ (2003) Mechanisms for a novel immune evasion strategy in the scabies mite Sarcoptes scabiei: a multigene family of inactivated serine proteases. J Invest Dermatol 121:1419–1424

    Article  PubMed  CAS  Google Scholar 

  • Jones AK, Sattelle DB (2006) The cys-loop ligand-gated ion channel superfamily of the honeybee, Apis mellifera. Invert Neurosci 6:123–132

    Article  PubMed  CAS  Google Scholar 

  • Kane NS, Hirschberg B, Qian S, Hunt D, Thomas B, Brochu R, Ludmerer SW, Zheng Y, Smith M, Arena JP, Cohen CJ, Schmatz D, Warmke J, Cully DF (2000) Drug resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin. Proc Natl Acad Sci USA 97:13949–13954

    Article  PubMed  CAS  Google Scholar 

  • Lawrence G, Leafasia J, Sheridan J, Hills S, Wate J, Wate C, Montgomery J, Pandeya N, Purdie D (2005) Control of scabies, skin sores and haematuria in children in the Solomon Islands: another role for ivermectin. Bull World Health Organ 83:34–42

    PubMed  Google Scholar 

  • McDonald M, Currie BJ, Carapetis JR (2004) Acute rheumatic fever: a chink in the chain that links the heart to the throat? Lancet Infect Dis 4:240–245

    Article  PubMed  Google Scholar 

  • Mounsey KE, Holt DC, McCarthy J, Walton SF (2006) Identification of ABC transporters in Sarcoptes scabiei. Parasitology 132:883–892

    Article  PubMed  CAS  Google Scholar 

  • Nielsen H, Krogh A (2004) Improved prediction of signal peptides: SignalP 3.0. J Mol Biol 340:783–795

    Article  PubMed  CAS  Google Scholar 

  • Njue AI, Hayashi J, Kinne L, Feng XP, Prichard RK (2004) Mutations in the extracellular domains of glutamate gated chloride channel α3 and β subunits from ivermectin-resistant Cooperia oncophora affect agonist sensitivity. J Neurochem 89:1137–1147

    Article  PubMed  CAS  Google Scholar 

  • Pemberton DJ, Franks CJ, Walker RJ, Holden-Dye L (2001) Characterisation of glutamate-gated chloride channels in the pharynx of wild-type and mutant Caenorhabditis elegans delineates the role of the subunit GluCl-a2 in the function of the native receptor. Mol Pharmacol 59:1037–1043

    PubMed  CAS  Google Scholar 

  • Putrenko I, Zakikhani M, Dent JA (2005) A family of acetylcholine-gated chloride channel subunits in Caenorhabditis elegans. J Biol Chem 280:6392–6398

    Article  PubMed  CAS  Google Scholar 

  • Ranganathan R, Cannon SC, Horvitz HR (2000) MOD-1 is a serotonin-gated chloride channel that modulates locomotory behaviour in C. elegans. Nature 408:470–475

    Article  PubMed  CAS  Google Scholar 

  • Roberts LJ, Huffam SE, Walton SF, Currie BJ (2005) Crusted scabies: clinical and immunological findings in seventy-eight patients and a review of the literature. J Infect 50:375–381

    Article  PubMed  CAS  Google Scholar 

  • Schnizler K, Saeger B, Pfeffer C, Gerbaulet A, Ebbinghaus-Kintscher U, Methfessel C, Franken EM, Raming K, Wetzel CH, Saras A, Pusch H, Hatt H, Gisselmann G (2005) A novel chloride channel in Drosophila melanogaster is inhibited by protons. J Biol Chem 280:16254–16262

    Article  PubMed  CAS  Google Scholar 

  • Walton SF, Currie BJ (2007) Problems in diagnosing scabies, a global disease in human and animal populations. Clin Microbiol Rev 20:268–279

    Article  PubMed  Google Scholar 

  • Wolstenholme AJ, Fairweather I, Prichard RK, von Samson-Himmelstjerna G, Sangster NC (2004) Drug resistance in veterinary helminths. Trends Parasitol 20:379–476

    Article  CAS  Google Scholar 

  • Zheng Y, Priest B, Cully DF, Ludmerer SW (2003) RdlDv, a novel GABA-gated chloride channel gene from the American dog tick Dermacentor variabilis. Insect Biochem Mol Biol 33:595–599

    PubMed  CAS  Google Scholar 

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Acknowledgemnts

This work was supported by the Australian National Health and Medical Research Council Project Grant 283301. KEM was supported by a Cooperative Research Centre for Aboriginal Health postgraduate research scholarship. We thank the ARC/NHMRC network for Parasitology for providing a travel award to KEM.

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Authors and Affiliations

  1. Menzies School of Health Research, Institute of Advanced Studies, Charles Darwin University, Darwin, NT, Australia

    Kate E. Mounsey, Deborah C. Holt, Bart J. Currie & Shelley F. Walton

  2. Department of Biology, McGill University, Montreal, QC, Canada

    Joseph A. Dent

  3. Queensland Institute of Medical Research and Australian Centre for International and Tropical Health and Nutrition, University of Queensland, Brisbane, QLD, Australia

    James McCarthy

  4. Northern Territory Clinical School, Flinders University, Darwin, NT, Australia

    Bart J. Currie

  5. Menzies School of Health Research, PO Box 41096, Casuarina, NT 0811, Australia

    Kate E. Mounsey

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  1. Kate E. Mounsey
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  2. Joseph A. Dent
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  3. Deborah C. Holt
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  4. James McCarthy
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  5. Bart J. Currie
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  6. Shelley F. Walton
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Correspondence to Kate E. Mounsey.

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Mounsey, K.E., Dent, J.A., Holt, D.C. et al. Molecular characterisation of a pH-gated chloride channel from Sarcoptes scabiei . Invert Neurosci 7, 149–156 (2007). https://doi.org/10.1007/s10158-007-0050-6

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  • DOI: https://doi.org/10.1007/s10158-007-0050-6

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