Australian funnel-web spiders evolved human-lethal δ-hexatoxins for defense against vertebrate predators

Volker Herzig; Kartik Sunagar; David Wilson; Sandy S Pineda; Mathilde R Israel; Sebastien Dutertre; Brianna Sollod McFarland; Eivind A B Undheim; Wayne C Hodgson; Paul F Alewood; Richard J Lewis; Frank Bosmans; Irina Vetter; Glenn F King; Bryan G Fry

doi:10.1073/pnas.2004516117

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Australian funnel-web spiders evolved human-lethal δ-hexatoxins for defense against vertebrate predators

Journal article

Peer reviewed

Australian funnel-web spiders evolved human-lethal δ-hexatoxins for defense against vertebrate predators

Volker Herzig, Kartik Sunagar, David Wilson, Sandy S Pineda, Mathilde R Israel, Sebastien Dutertre, Brianna Sollod McFarland, Eivind A B Undheim, Wayne C Hodgson, Paul F Alewood, …

Proceedings of the National Academy of Sciences, Vol.117(40), pp.24920-24928

2020

DOI: https://doi.org/10.1073/pnas.2004516117

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Abstract

venom

evolution

spider

Australian funnel-web spiders are infamous for causing human fatalities, which are induced by venom peptides known as δ-hexatoxins (δ-HXTXs). Humans and other primates did not feature in the prey or predator spectrum during evolution of these spiders, and consequently the primate lethality of δ-HXTXs remains enigmatic. Funnel-web envenomations are mostly inflicted by male spiders that wander from their burrow in search of females during the mating season, which suggests a role for δ-HXTXs in self-defense since male spiders rarely feed during this period. Although 35 species of Australian funnel-web spiders have been described, only nine δ-HXTXs from four species have been characterized, resulting in a lack of understanding of the ecological roles and molecular evolution of δ-HXTXs. Here, by profiling venom-gland transcriptomes of 10 funnel-web species, we report 22 δ-HXTXs. Phylogenetic and evolutionary assessments reveal a remarkable sequence conservation of δ-HXTXs despite their deep evolutionary origin within funnel-web spiders, consistent with a defensive role. We demonstrate that δ-HXTX-Ar1a, the lethal toxin from the Sydney funnel-web spider Atrax robustus, induces pain in mice by inhibiting inactivation of voltage-gated sodium (NaV) channels involved in nociceptive signaling. δ-HXTX-Ar1a also inhibited inactivation of cockroach NaV channels and was insecticidal to sheep blowflies. Considering their algogenic effects in mice, potent insecticidal effects, and high levels of sequence conservation, we propose that the δ-HXTXs were repurposed from an initial insecticidal predatory function to a role in defending against nonhuman vertebrate predators by male spiders, with their lethal effects on humans being an unfortunate evolutionary coincidence.

Details

Title: Australian funnel-web spiders evolved human-lethal δ-hexatoxins for defense against vertebrate predators
Authors: Volker Herzig (Author) - University of the Sunshine Coast, Queensland, School of Science and Engineering - Legacy
Kartik Sunagar (Author) - Indian Institute of Science Bangalore
David Wilson (Author) - James Cook University
Sandy S Pineda (Author) - The University of Queensland
Mathilde R Israel (Author) - The University of Queensland
Sebastien Dutertre (Author) - Université de Montpellier
Brianna Sollod McFarland (Author) - Sollod Scientific Analysis
Eivind A B Undheim (Author) - The University of Queensland
Wayne C Hodgson (Author) - Monash University
Paul F Alewood (Author) - The University of Queensland
Richard J Lewis (Author) - The University of Queensland
Frank Bosmans (Author) - Ghent University
Irina Vetter (Author) - The University of Queensland
Glenn F King (Author) - The University of Queensland
Bryan G Fry (Author) - The University of Queensland
Publication details: Proceedings of the National Academy of Sciences, Vol.117(40), pp.24920-24928
Publisher: National Academy of Sciences
Date published: 2020
DOI: 10.1073/pnas.2004516117
ISSN: 1091-6490
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
The role of ion channels in pain pathways, 1162503, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Venoms to drugs: translating venom peptides into human therapeutics, 1136889, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Functional evolution and therapeutic potential of snake venom coagulotoxins, DP190100304, Australian Research Council (Australia, Canberra) - ARC
Grant note: K.S. was supported by the Department of Science and Technology (DST) INSPIRE Faculty Award (DST/INSPIRE/04/2017/000071), DST - Fund for Improvement of S&T Infrastructure in Higher Educational Institutions (DST-FIST) (SR/FST/LS-II/2018/233), and the Department of Biotechnology-Indian Institute of Science (DBT-IISc) Partnership Program. I.V. was supported by an Early Career Researcher (ECR) grant from The Clive & Vera Ramaciotti Foundation.
Organisation Unit: School of Science and Engineering - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99480008702621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Biochemistry & Molecular Biology

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