The Deadly Toxin Arsenal of the Tree-Dwelling Australian Funnel-Web Spiders

Fernanda C. Cardoso; Sandy S. Pineda; Volker Herzig; Kartik Sunagar; Naeem Yusuf Shaikh; Ai-Hua Jin; Glenn F. King; Paul F. Alewood; Richard J. Lewis; Sébastien Dutertre

doi:10.3390/ijms232113077

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The Deadly Toxin Arsenal of the Tree-Dwelling Australian Funnel-Web Spiders

Journal article

Open access

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The Deadly Toxin Arsenal of the Tree-Dwelling Australian Funnel-Web Spiders

Fernanda C. Cardoso, Sandy S. Pineda, Volker Herzig, Kartik Sunagar, Naeem Yusuf Shaikh, Ai-Hua Jin, Glenn F. King, Paul F. Alewood, Richard J. Lewis and Sébastien Dutertre

International Journal of Molecular Sciences, Vol.23(21), pp.1-17

2022

DOI: https://doi.org/10.3390/ijms232113077

PMCID: PMC9658043

PMID: 36361863

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Abstract

arboreal

deadliest spider

Hadronyche

ion channels

neurotoxins

venom

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 (Atrax robustus); 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 Hadronyche cerberea and H. formidabilis. Overall, Hadronyche 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 Hadronyche venom on sheep blowflies were more potent than Atrax venom, and the venom of both tree- and ground-dwelling species potently modulated human voltage-gated sodium channels, particularly NaV1.2. Only the venom of tree-dwellers exhibited potent modulation of voltage-gated calcium channels. H. formidabilis appeared to be under less diversifying selection pressure compared to the newly adapted tree-dweller, H. cerberea. 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.

Details

Title: The Deadly Toxin Arsenal of the Tree-Dwelling Australian Funnel-Web Spiders
Authors: Fernanda C. Cardoso (Author) - The University of Queensland
Sandy S. Pineda (Author) - The University of Queensland
Volker Herzig (Author) - University of the Sunshine Coast, Queensland, Centre for Bioinnovation
Kartik Sunagar (Author) - Indian Institute of Science Bangalore
Naeem Yusuf Shaikh (Author) - Indian Institute of Science Bangalore
Ai-Hua Jin (Author) - The University of Queensland
Glenn F. King (Author) - The University of Queensland
Paul F. Alewood (Author) - The University of Queensland
Richard J. Lewis (Author) - The University of Queensland
Sébastien Dutertre (Corresponding Author) - Université de Montpellier
Publication details: International Journal of Molecular Sciences, Vol.23(21), pp.1-17
Publisher: MDPI AG
Date published: 2022
DOI: 10.3390/ijms232113077
ISSN: 1422-0067
PMID: 36361863; PMC9658043
Copyright note: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Grants: Be(e) friendly venomous spiders! Novel biopesticides from arachnid venoms, FT190100482, Australian Research Council (Australia, Canberra) - ARC
Discovery and development of better pain treatments, 1072113, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Novel multifunctional analgesic sodium channel inhibitors, 1188959, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Discovery and development of novel venom peptide analgesics, 1119056, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Grant note: IA/I/19/2/504647 / DBT/Welcome Trust India Alliance Fellowship; ANR-16-CE34-0002 / French National Research Agency
Organisation Unit: School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99690998802621
Output Type: Journal article

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