Identification and Functional Expression of a Glutamate- and Avermectin-Gated Chloride Channel from , a Southern Hemisphere Sea Louse Affecting Farmed Fish

English version České info

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

Zdroje

1. CostelloMJ (2006) Ecology of sea lice parasitic on farmed and wild fish. Trends Parasitol 22 : 475–483 S1471-4922(06)00211-X [pii];10.1016/j.pt.2006.08.006 [doi]

2. BoxshallGA, BravoS (2000) On the identity of the common Caligus (Copepoda: Siphonostomatoida: Caligidae) from salmonid netpen systems in southern Chile. Contrib Zool 69 : 137–146.

3. TorrissenO, JonesS, AscheF, GuttormsenA, SkilbreiOT, et al. (2013) Salmon lice-impact on wild salmonids and salmon aquaculture. J Fish Dis 36 : 171–194 10.1111/jfd.12061 [doi]

4. DentJA, DavisMW, AveryL (1997) avr-15 encodes a chloride channel subunit that mediates inhibitory glutamatergic neurotransmission and ivermectin sensitivity in Caenorhabditis elegans. EMBO J 16 : 5867–5879 10.1093/emboj/16.19.5867 [doi]

5. WolstenholmeAJ, FairweatherI, PrichardR, von Samson-HimmelstjernaG, SangsterNC (2004) Drug resistance in veterinary helminths. Trends Parasitol 20 : 469–476 10.1016/j.pt.2004.07.010 [doi];S1471-4922(04)00201-6 [pii]

6. JonesAK, SattelleDB (2006) The cys-loop ligand-gated ion channel superfamily of the honeybee, Apis mellifera. Invert Neurosci 6 : 123–132 10.1007/s10158-006-0026-y [doi]

7. JonesAK, SattelleDB (2007) The cys-loop ligand-gated ion channel gene superfamily of the red flour beetle, Tribolium castaneum. BMC Genomics 8 : 327 1471-2164-8-327 [pii];10.1186/1471-2164-8-327 [doi]

8. JonesAK, SattelleDB (2008) The cys-loop ligand-gated ion channel gene superfamily of the nematode, Caenorhabditis elegans. Invert Neurosci 8 : 41–47 10.1007/s10158-008-0068-4 [doi]

9. KnippleDC, SoderlundDM (2010) The ligand-gated chloride channel gene family of Drosophila melanogaster. Pest Biochem Physiol 97 : 140–148.

10. RaymondV, SattelleDB (2002) Novel animal-health drug targets from ligand-gated chloride channels. Nat Rev Drug Discov 1 : 427–436 10.1038/nrd821 [doi]

11. CullyDF, VassilatisDK, LiuKK, ParessPS, Van der PloegLH, et al. (1994) Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature 371 : 707–711 10.1038/371707a0 [doi]

12. VassilatisDK, ArenaJP, PlasterkRH, WilkinsonHA, SchaefferJM, et al. (1997) Genetic and biochemical evidence for a novel avermectin-sensitive chloride channel in Caenorhabditis elegans. Isolation and characterization. J Biol Chem 272 : 33167–33174.

13. CheesemanCL, DelanyNS, WoodsDJ, WolstenholmeAJ (2001) High-affinity ivermectin binding to recombinant subunits of the Haemonchus contortus glutamate-gated chloride channel. Mol Biochem Parasitol 114 : 161–168 S0166685101002584 [pii]

14. WolstenholmeAJ (2012) Glutamate-gated chloride channels. J Biol Chem 287 : 40232–40238 R112.406280 [pii];10.1074/jbc.R112.406280 [doi]

15. CullyDF, WilkinsonH, VassilatisDK, EtterA, ArenaJP (1996) Molecular biology and electrophysiology of glutamate-gated chloride channels of invertebrates. Parasitology 113 Suppl: S191–S200.

16. HibbsRE, GouauxE (2011) Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474 : 54–60 nature10139 [pii];10.1038/nature10139 [doi]

17. BravoS, SevatdalS, HorsbergTE (2008) Sensitivity assessment of Caligus rogercresseyi to emamectin benzoate in Chile. Aquaculture 282 : 7–12.

18. HuangJC, ChenF (2006) Simultaneous amplification of 5′ and 3′ cDNA ends based on template-switching effect and inverse PCR. Biotechniques 40 : 187–189 000112051 [pii]

19. SaliA, BlundellTL (1993) Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234 : 779–815.

20. PhillipsJC, BraunR, WangW, GumbartJ, TajkhorshidE, et al. (2005) Scalable molecular dynamics with NAMD. J Comput Chem 26 : 1781–1802 10.1002/jcc.20289 [doi]

21. Glide (2012) 5.8 [computer program]. New York NY USA: Schrödinger LLC.

22. Maestro (2012) 9.3 [computer program]. New York NY USA: Schrödinger LLC.

23. LigPrep (2012) 2.5 [computer program]. New York NY USA: Schrödinger LLC.

24. SastryGM, AdzhigireyM, DayT, AnnabhimojuR, ShermanW (2013) Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des 27 : 221–234 10.1007/s10822-013-9644-8 [doi]

25. JorgensenWL, ChandrasekharJ, MaduraJD, ImpeyRW, KleinMI (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79 : 926–935.

26. TuckermanME, MartynaGJ, BerneBJ (1992) Reversible multiple time scale molecular dynamics. J Chem Phys 97 : 1990–2001.

27. SmartOS, NeduvelilJG, WangX, WallaceBA, SansomMS (1996) HOLE: a program for the analysis of the pore dimensions of ion channel structural models. J Mol Graph 14 : 354–60, 376 S026378559700009X [pii]

28. TakeuchiA, TakeuchiN (1969) A study of the action of picrotoxin on the inhibitory neuromuscular junction of the crayfish. J Physiol 205 : 377–391.

29. EtterA, CullyDF, LiuKK, ReissB, VassilatisDK, et al. (1999) Picrotoxin blockade of invertebrate glutamate-gated chloride channels: subunit dependence and evidence for binding within the pore. J Neurochem 72 : 318–326.

30. MilediR, ParkerI (1984) Chloride current induced by injection of calcium into Xenopus oocytes. J Physiol 357 : 173–183.

31. ChengMH, CoalsonRD (2012) Energetics and ion permeation characteristics in a glutamate-gated chloride (GluCl) receptor channel. J Phys Chem B 116 : 13637–13643 10.1021/jp3074915 [doi]

32. CalimetN, SimoesM, ChangeuxJP, KarplusM, TalyA, et al. (2013) A gating mechanism of pentameric ligand-gated ion channels. Proc Natl Acad Sci U S A 110: E3987–E3996 1313785110 [pii];10.1073/pnas.1313785110 [doi]

33. HorsbergTE (2012) Avermectin use in aquaculture. Curr Pharm Biotechnol 13 : 1095–1102 BSP/CPB/E-Pub/0000125 [pii]

34. BravoS, NunezM, SilvaMT (2013) Efficacy of the treatments used for the control of Caligus rogercresseyi infecting Atlantic salmon, Salmo salar L., in a new fish-farming location in Region XI, Chile. J Fish Dis 36 : 221–228 10.1111/jfd.12023 [doi]

35. LeesF, BaillieM, GettinbyG, RevieCW (2008) The efficacy of emamectin benzoate against infestations of Lepeophtheirus salmonis on farmed Atlantic salmon (Salmo salar L) in Scotland, 2002–2006. PLoS ONE 3: e1549 10.1371/journal.pone.0001549 [doi]

36. IgboeliOO, BurkaJF, FastMD (2013) Sea lice population and sex differences in P-glycoprotein expression and emamectin benzoate resistance on salmon farms in the Bay of Fundy, New Brunswick, Canada. Pest Manag Sci 10.1002/ps.3620 [doi]

37. DentJA, SmithMM, VassilatisDK, AveryL (2000) The genetics of ivermectin resistance in Caenorhabditis elegans. Proc Natl Acad Sci U S A 97 : 2674–2679 97/6/2674 [pii]

38. KaneNS, HirschbergB, QianS, HuntD, ThomasB, et al. (2000) Drug-resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin. Proc Natl Acad Sci U S A 97 : 13949–13954.

39. LynaghT, LynchJW (2010) A glycine residue essential for high ivermectin sensitivity in Cys-loop ion channel receptors. Int J Parasitol 40 : 1477–1481 S0020-7519(10)00281-X [pii];10.1016/j.ijpara.2010.07.010 [doi]

40. TribbleND, BurkaJF, KibengeFS (2007) Identification of the genes encoding for putative gamma aminobutyric acid (GABA) and glutamate-gated chloride channel (GluCl) alpha receptor subunits in sea lice (Lepeophtheirus salmonis). J Vet Pharmacol Ther 30 : 163–167 JVP823 [pii];10.1111/j.1365-2885.2007.00823.x [doi]

41. Young PD (2008) Binding characteristics of emamectin benzoate to the putative glutamate-gated chloride channels of Lepeophtheirus salmonis [dissertation]. University of Prince Edward Island, Canada. 108 p.

42. CullyDF, ParessPS, LiuKK, SchaefferJM, ArenaJP (1996) Identification of a Drosophila melanogaster glutamate-gated chloride channel sensitive to the antiparasitic agent avermectin. J Biol Chem 271 : 20187–20191.

43. EtterA, CullyDF, SchaefferJM, LiuKK, ArenaJP (1996) An amino acid substitution in the pore region of a glutamate-gated chloride channel enables the coupling of ligand binding to channel gating. J Biol Chem 271 : 16035–16039.

44. LynaghT, LynchJW (2012) Ivermectin binding sites in human and invertebrate Cys-loop receptors. Trends Pharmacol Sci 33 : 432–441 S0165-6147(12)00074-0 [pii];10.1016/j.tips.2012.05.002 [doi]

45. ForresterSG, HamdanFF, PrichardRK, BeechRN (1999) Cloning, sequencing, and developmental expression levels of a novel glutamate-gated chloride channel homologue in the parasitic nematode Haemonchus contortus. Biochem Biophys Res Commun 254 : 529–534 S0006-291X(98)90106-1 [pii];10.1006/bbrc.1998.0106 [doi]

46. ForresterSG, PrichardRK, DentJA, BeechRN (2003) Haemonchus contortus: HcGluCla expressed in Xenopus oocytes forms a glutamate-gated ion channel that is activated by ibotenate and the antiparasitic drug ivermectin. Mol Biochem Parasitol 129 : 115–121 S0166685103001026 [pii]

47. BodeA, LynchJW (2013) Analysis of hyperekplexia mutations identifies transmembrane domain rearrangements that mediate glycine receptor activation. J Biol Chem 288 : 33760–33771 M113.513804 [pii];10.1074/jbc.M113.513804 [doi]

48. KwonDH, YoonKS, ClarkJM, LeeSH (2010) A point mutation in a glutamate-gated chloride channel confers abamectin resistance in the two-spotted spider mite, Tetranychus urticae Koch. Insect Mol Biol 19 : 583–591 IMB1017 [pii];10.1111/j.1365-2583.2010.01017.x [doi]

49. CorringerPJ, PoitevinF, PrevostMS, SauguetL, DelarueM, et al. (2012) Structure and pharmacology of pentameric receptor channels: from bacteria to brain. Structure 20 : 941–956 S0969-2126(12)00184-0 [pii];10.1016/j.str.2012.05.003 [doi]