Aedes aegypti mosquitoes are important vectors of arboviruses such as chikungunya, dengue, yellow fever and Zika viruses [1], accounting for over 29,000 annual deaths with up to one third of the worlds’ population at risk, particularly in Africa, the Americas, Asia and the Pacific [2]. Effective and rapid control of these diseases relies on vector control, which is mainly achieved using chemical insecticides [3]. However, A. aegypti have been reported to be resistant to many existing chemical insecticides [4]. Thus, our study aimed at isolating mosquitocidal toxins by screening venoms sourced from 41 spider and 9 scorpion species. These screens revealed potent mosquitocidal activity in the venom of the Cameroon baboon tarantula Hysterocrates gigas. Using a combination of reversed phase and hydrophilic interaction liquid chromatography, we isolated a 40-residue peptide with an oxidized monoisotopic mass of 4502.11 Da which was named U1-TRTX-Hg1a (Hg1a) [5]. When injected into A. aegypti mosquito, the isolated Hg1a showed a LD50 of 23.2 pmol/g. In silico modelling using SwissModel predicts that the 3-dimensional structure of Hg1a conforms to the disulfide directed β-hairpin (DDH) motif having three parallel β-strands, which are stabilized by three disulfide bonds. A BLAST search using NCBI and Arachnoserver [6,7] revealed 65-72.5% sequence similarities between Hg1a and several insecticidal toxins from other tarantula species, with ⍵-TRTX-Asp1a [8] exhibiting the highest similarity. Phylogenetic analysis of Hg1a with these similar toxins using MEGA X revealed that Hg1a is closely related to U1-TRTX-Hs1a, a toxin isolated from the Chinese tarantula Cyriopagopus schmidti [9] sharing 68.3% sequence similarity. Hg1a is the first insecticidal toxin isolated from H. gigas venom with the potential to be used as a lead for controlling A. aegypti mosquitoes.
Key words: Hysterocrates gigas tarantula, insecticidal toxin, Aedes aegypti mosquito, disulfide directed β-hairpin