Tick holocyclotoxins trigger host paralysis by presynaptic inhibition.

Kirat K Chand,Johannes Koehbach,Ala Lew-Tabor,Hina Ijaz,Nickolas A Lavidis,Kah Meng Lee,Peter G Noakes,Manuel Rodriguez-Valle,Richard J Clark

doi:10.1038/srep29446

Kirat K Chand, Johannes Koehbach + Show 7 more

Open Access

https://doi.org/10.1038/srep29446

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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.

Highlights

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 current study reports 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
Transmitter release from motor nerve terminals requires a number of prerequisites to be met: activation of P/Q-type voltage gated calcium channels (VGCCs), entry of calcium ions close to the active zone, the formation of calcium micro domains, localisation of vesicles close to the VGCCs and co-localisation of key vesicular proteins close to the vesicle and VGCCs12

Summary

Introduction

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. 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. Ticks (order Acarina) are arthropods members of the class Arachnida, which includes spiders (order Araneae) and scorpions (order Scorpionida) These ectoparasites need to feed on the host’s blood to complete their life cycle and secrete a complex mixture of proteins in the saliva to counter host defenses[1,2,3,4,5]. Previous study conducted by Cooper and co-worker indicated that I. holocyclus (Iho) toxins inhibit the release of acetylcholine from neuromuscular junction to cause paralysis[11]. The current study reports 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

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