Coagulating colubrids: evolutionary, pathophysiological and biodiscovery implications of venom variations between boomslang (Dispholidus typus) and twig snake (Thelotornis mossambicanus)

Debono, Jordan, Dobson, James, Casewell, Nicholas R., Romilio, Anthony, Li, Bin, Kurniawan, Nyoman, Mardon, Karine, Weisbecker, Vera, Nouwens, Amanda, Kwok, Hang Fai and Fry, Bryan G. (2017) Coagulating colubrids: evolutionary, pathophysiological and biodiscovery implications of venom variations between boomslang (Dispholidus typus) and twig snake (Thelotornis mossambicanus). Toxins, 9 5: . doi:10.3390/toxins9050171


Author Debono, Jordan
Dobson, James
Casewell, Nicholas R.
Romilio, Anthony
Li, Bin
Kurniawan, Nyoman
Mardon, Karine
Weisbecker, Vera
Nouwens, Amanda
Kwok, Hang Fai
Fry, Bryan G.
Title Coagulating colubrids: evolutionary, pathophysiological and biodiscovery implications of venom variations between boomslang (Dispholidus typus) and twig snake (Thelotornis mossambicanus)
Formatted title
Coagulating colubrids: evolutionary, pathophysiological and biodiscovery implications of venom variations between boomslang (Dispholidus typus) and twig snake (Thelotornis mossambicanus)
Journal name Toxins   Check publisher's open access policy
ISSN 2072-6651
Publication date 2017-05-19
Sub-type Article (original research)
DOI 10.3390/toxins9050171
Open Access Status DOI
Volume 9
Issue 5
Total pages 20
Place of publication Basel, Switzerland
Publisher M D P I AG
Language eng
Abstract 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.
Formatted abstract
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.
Keyword Dispholidus typus
Thelotornis mossambicanus
Biodiscovery
Boomslang
Colubridae
Enzyme activity
Evolution
Procoagulant
Q-Index Code C1

 
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Created: Fri, 26 May 2017, 09:24:31 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences