Coagulating Colubrids: Evolutionary, Pathophysiological and Biodiscovery Implications of Venom Variations between Boomslang (Dispholidus typus) and Twig Snake (Thelotornis mossambicanus)
| Autor: | Nyoman D. Kurniawan, Amanda Nouwens, Vera Weisbecker, James Dobson, Karine Mardon, Hang Fai Kwok, Bryan G. Fry, Jordan Debono, Anthony Romilio, Nicholas R. Casewell, Bin Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteomics Dispholidus typus Health Toxicology and Mutagenesis Antivenom Zoology lcsh:Medicine Venom Reptilian Proteins Biology Phospholipase procoagulant boomslang Thelotornis mossambicanus colubridae enzyme activity biodiscovery evolution Toxicology complex mixtures Article 03 medical and health sciences Exocrine Glands Colubridae Animals Humans Blood Coagulation wh_310 Boomslang Antivenins lcsh:R Skull Anatomy Kallikrein biology.organism_classification Biological Evolution Twig snake Phospholipases A2 030104 developmental biology Coagulation Metalloproteases Kallikreins qy_410 wd_410 Snake Venoms |
| Zdroj: | Toxins Toxins; Volume 9; Issue 5; Pages: 171 Toxins, Vol 9, Iss 5, p 171 (2017) |
| ISSN: | 2072-6651 |
| Popis: | Venoms can deleteriously affect any physiological system reachable by the bloodstream, including directly interfering with the coagulation cascade. Such coagulopathic toxins may be anticoagulants or procoagulants. Snake venoms are unique in their use of procoagulant toxins for predatory purposes. The boomslang (Dispholidus typus) and the twig snakes (Thelotornis species) are iconic African snakes belonging to the family Colubridae. Both species produce strikingly similar lethal procoagulant pathologies. Despite these similarities, antivenom is only produced for treating bites by D. typus, and the mechanisms of action of both venoms have been understudied. In this study, we investigated the venom of D. typus and T. mossambicanus utilising a range of proteomic and bioactivity approaches, including determining the procoagulant properties of both venoms in relation to the human coagulation pathways. In doing so, we developed a novel procoagulant assay, utilising a Stago STA-R Max analyser, to accurately detect real time clotting in plasma at varying concentrations of venom. This approach was used to assess the clotting capabilities of the two venoms both with and without calcium and phospholipid co-factors. We found that T. mossambicanus produced a significantly stronger coagulation response compared to D. typus. Functional enzyme assays showed that T. mossambicanus also exhibited a higher metalloprotease and phospholipase activity but had a much lower serine protease activity relative to D. typus venom. The neutralising capability of the available boomslang antivenom was also investigated on both species, with it being 11.3 times more effective upon D. typus venom than T. mossambicanus. In addition to being a faster clotting venom, T. mossambicanus was revealed to be a much more complex venom composition than D. typus. This is consistent with patterns seen for other snakes with venom complexity linked to dietary complexity. Consistent with the external morphological differences in head shape between the two species, CT and MRI analyses revealed significant internal structural differences in skull architecture and venom gland anatomy. This study increases our understanding of not only the biodiscovery potential of these medically important species but also increases our knowledge of the pathological relationship between venom and the human coagulation cascade. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|