title: Tick holocyclotoxins trigger host paralysis by presynaptic inhibition.
abstract: Ticks are important vectors of pathogens and secreted neurotoxins with approximately 69 out of 692 tick species having the ability to induce severe toxicoses in their hosts. The Australian paralysis tick (Ixodes holocyclus) is known to be one of the most virulent tick species producing a flaccid paralysis and fatalities caused by a family of neurotoxins known as holocyclotoxins (HTs). The paralysis mechanism of these toxins is temperature dependent and is thought to involve inhibition of acetylcholine levels at the neuromuscular junction. However, the target and mechanism of this inhibition remain uncharacterised. Here, we report that three members of the holocyclotoxin family; HT-1 (GenBank AY766147), HT-3 (GenBank KP096303) and HT-12 (GenBank KP963967) induce muscle paralysis by inhibiting the dependence of transmitter release on extracellular calcium. Previous study was conducted using extracts from tick salivary glands, while the present study is the first to use pure toxins from I. holocyclus. Our findings provide greater insight into the mechanisms by which these toxins act to induce paralysis.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, 4067, Australia.
authors.forename: Kirat K
authors.initials: KK
authors.lastname: Chand
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, 4067, Australia.
authors.forename: Kah Meng
authors.initials: KM
authors.lastname: Lee
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, 4067, Australia.
authors.forename: Nickolas A
authors.initials: NA
authors.lastname: Lavidis
authors.affiliation: Queensland Alliance for Agriculture &Food Innovation, The University of Queensland, QLD, Australia.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodriguez-Valle
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, 4067, Australia.
authors.forename: Hina
authors.initials: H
authors.lastname: Ijaz
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, 4067, Australia.
authors.forename: Johannes
authors.initials: J
authors.lastname: Koehbach
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, 4067, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Clark
authors.affiliation: Queensland Alliance for Agriculture &Food Innovation, The University of Queensland, QLD, Australia.|Centre for Comparative Genomics, Murdoch University, Perth, WA 6150, Australia.
authors.forename: Ala
authors.initials: A
authors.lastname: Lew-Tabor
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, 4067, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Noakes
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001180:Arthropod Venoms / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D005260:Female; D018884:Ixodes / Q000378:metabolism*; D051379:Mice; D009045:Motor Endplate / Q000187:drug effects* / Q000502:physiology; D005810:Multigene Family; D009435:Synaptic Transmission / Q000187:drug effects*; D013696:Temperature; D013985:Tick Paralysis / Q000139:chemically induced* / Q000378:metabolism
chemical_list: D001180:Arthropod Venoms; C038423:holocyclotoxin; D000109:Acetylcholine; D002118:Calcium