Tick Paralysis: Solving an Enigma

Abstract

In comparison to other arachnids, ticks are major vectors of disease, but less than 8% of the known species are capable of inducing paralysis, as compared to the ~99⁻100% arachnids that belong to venomous classes. When considering the potential monophyly of venomous Arachnida, this review reflects on the implications regarding the classification of ticks as venomous animals and the possible origin of toxins. The origin of tick toxins is compared with scorpion and spider toxins and venoms based on their significance, functionality, and structure in the search to find homologous venomous characters. Phenotypic evaluation of paralysis, as caused by different ticks, demonstrated the need for expansion on existing molecular data of pure isolated tick toxins because of differences and discrepancies in available data. The use of in-vivo, in-vitro, and in-silico assays for the purification and characterization of paralysis toxins were critically considered, in view of what may be considered to be a paralysis toxin. Purified toxins should exhibit physiologically relevant activity to distinguish them from other tick-derived proteins. A reductionist approach to identify defined tick proteins will remain as paramount in the search for defined anti-paralysis vaccines.

Keywords: blood-feeding; tick evolution; tick paralysis; tick toxicoses; toxin; venom.

Figure 1

Phylogenetic relationships of the 73 ixodid and argasid tick species that were implicated in paralysis adapted from [36]. Broken branch lines indicate genera that are implicated in paralysis. Numbers in brackets indicate the number of species implicated in paralysis or paresis as updated [10], followed by the total number of species [4].

Figure 2

Alignment of the Ixodes holocyclus holocyclotoxins (HT) with members of the Ixodes scapularis (Iscap) and Ixodes pacificus (Ipac) 5.3 kDa family as well as a member from Argas monolakensis (Amon) followed by their corresponding Genbank accession numbers. Conserved residues are shaded in black and disulphide bonds from holocyclotoxin are indicated. The cysteine patterns of the canonical inhibitory cysteine knot (ICK) motif and the cyclotide variant pattern and the 3/4 cysteine doublet are indicated (cysteine 5–6 in holocyclotoxin). The cysteine number for the canonical ICK motif is indicated below the disulphide bonds.

Figure 3

Structures of ion channel inhibitors from ticks. Indicated are holocyclotoxin from Ixodes holocyclus displaying the ICK motif, Ixodes scapularis neurotoxin I (ISTX-I) that does not possess a ICK motif and the activator of Ca²⁺ activated potassium (K⁺) channels that were identified in R. appendiculatus, R. appendiculatus (Ra-KLP) that belongs to the Kunitz-BPTI fold.