The Deadly Toxin Arsenal of the Tree-Dwelling Australian Funnel-Web Spiders
Australian funnel-web spiders are amongst the most dangerous venomous animals. Their venoms induce potentially deadly symptoms, including hyper- and hypotension, tachycardia, bradycardia and pulmonary oedema. Human envenomation is more frequent with the ground-dwelling species, including the infamou...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/21/13077 |
| Summary: | Australian funnel-web spiders are amongst the most dangerous venomous animals. Their venoms induce potentially deadly symptoms, including hyper- and hypotension, tachycardia, bradycardia and pulmonary oedema. Human envenomation is more frequent with the ground-dwelling species, including the infamous Sydney funnel-web spider (<i>Atrax robustus</i>); although, only two tree-dwelling species induce more severe envenomation. To unravel the mechanisms that lead to this stark difference in clinical outcomes, we investigated the venom transcriptome and proteome of arboreal <i>Hadronyche cerberea</i> and <i>H. formidabilis</i>. Overall, <i>Hadronyche</i> venoms comprised 44 toxin superfamilies, with 12 being exclusive to tree-dwellers. Surprisingly, the major venom components were neprilysins and uncharacterized peptides, in addition to the well-known ω- and δ-hexatoxins and double-knot peptides. The insecticidal effects of <i>Hadronyche</i> venom on sheep blowflies were more potent than <i>Atrax</i> venom, and the venom of both tree- and ground-dwelling species potently modulated human voltage-gated sodium channels, particularly Na<sub>V</sub>1.2. Only the venom of tree-dwellers exhibited potent modulation of voltage-gated calcium channels. <i>H. formidabilis</i> appeared to be under less diversifying selection pressure compared to the newly adapted tree-dweller, <i>H. cerberea</i>. Thus, this study contributes to unravelling the fascinating molecular and pharmacological basis for the severe envenomation caused by the Australian tree-dwelling funnel-web spiders. |
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| ISSN: | 1661-6596 1422-0067 |