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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/21/13077 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Fernanda C. Cardoso |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T19:00:52Z |
| format | Article |
| id | doaj.art-abfd3208d54a4d95ab1ed26946d4da67 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:00:52Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-abfd3208d54a4d95ab1ed26946d4da672023-11-24T05:02:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211307710.3390/ijms232113077The Deadly Toxin Arsenal of the Tree-Dwelling Australian Funnel-Web SpidersFernanda C. Cardoso0Sandy S. Pineda1Volker Herzig2Kartik Sunagar3Naeem Yusuf Shaikh4Ai-Hua Jin5Glenn F. King6Paul F. Alewood7Richard J. Lewis8Sébastien Dutertre9Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, AustraliaEvolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, IndiaEvolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, IndiaInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, AustraliaIBMM, Université de Montpellier, CNRS, ENSCM, 34095 Montpellier, FranceAustralian 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.https://www.mdpi.com/1422-0067/23/21/13077venomneurotoxinsion channels<i>Hadronyche</i>deadliest spiderarboreal |
| spellingShingle | 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 The Deadly Toxin Arsenal of the Tree-Dwelling Australian Funnel-Web Spiders International Journal of Molecular Sciences venom neurotoxins ion channels <i>Hadronyche</i> deadliest spider arboreal |
| title | The Deadly Toxin Arsenal of the Tree-Dwelling Australian Funnel-Web Spiders |
| title_full | The Deadly Toxin Arsenal of the Tree-Dwelling Australian Funnel-Web Spiders |
| title_fullStr | The Deadly Toxin Arsenal of the Tree-Dwelling Australian Funnel-Web Spiders |
| title_full_unstemmed | The Deadly Toxin Arsenal of the Tree-Dwelling Australian Funnel-Web Spiders |
| title_short | The Deadly Toxin Arsenal of the Tree-Dwelling Australian Funnel-Web Spiders |
| title_sort | deadly toxin arsenal of the tree dwelling australian funnel web spiders |
| topic | venom neurotoxins ion channels <i>Hadronyche</i> deadliest spider arboreal |
| url | https://www.mdpi.com/1422-0067/23/21/13077 |
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