RESUMO
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.
Assuntos
Venenos de Artrópodes/toxicidade , Ixodes/metabolismo , Placa Motora/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Paralisia por Carrapato/induzido quimicamente , Acetilcolina/metabolismo , Animais , Cálcio/metabolismo , Feminino , Camundongos , Placa Motora/fisiologia , Família Multigênica , Temperatura , Paralisia por Carrapato/metabolismoRESUMO
Tick paralysis is a preventable cause of morbidity and death that, when diagnosed promptly, requires a simple low-cost intervention. The key to success is to consider tick paralysis in the differential diagnosis of ascending weakness, particularly in children, in geographic areas where this disease predominates.