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James Dobson
Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia, Qld 4072, Australia

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Journal article
Published: 06 August 2021 in Toxins
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Bites from helodermatid lizards can cause pain, paresthesia, paralysis, and tachycardia, as well as other symptoms consistent with neurotoxicity. Furthermore, in vitro studies have shown that Heloderma horridum venom inhibits ion flux and blocks the electrical stimulation of skeletal muscles. Helodermatids have long been considered the only venomous lizards, but a large body of robust evidence has demonstrated venom to be a basal trait of Anguimorpha. This clade includes varanid lizards, whose bites have been reported to cause anticoagulation, pain, and occasionally paralysis and tachycardia. Despite the evolutionary novelty of these lizard venoms, their neuromuscular targets have yet to be identified, even for the iconic helodermatid lizards. Therefore, to fill this knowledge gap, the venoms of three Heloderma species (H. exasperatum, H. horridum and H. suspectum) and two Varanus species (V. salvadorii and V. varius) were investigated using Gallus gallus chick biventer cervicis nerve–muscle preparations and biolayer interferometry assays for binding to mammalian ion channels. Incubation with Heloderma venoms caused the reduction in nerve-mediated muscle twitches post initial response of avian skeletal muscle tissue preparation assays suggesting voltage-gated sodium (NaV) channel binding. Congruent with the flaccid paralysis inducing blockage of electrical stimulation in the skeletal muscle preparations, the biolayer interferometry tests with Heloderma suspectum venom revealed binding to the S3–S4 loop within voltage-sensing domain IV of the skeletal muscle channel subtype, NaV1.4. Consistent with tachycardia reported in clinical cases, the venom also bound to voltage-sensing domain IV of the cardiac smooth muscle calcium channel, CaV1.2. While Varanus varius venom did not have discernable effects in the avian tissue preparation assay at the concentration tested, in the biointerferometry assay both V. varius and V. salvadorii bound to voltage-sensing domain IV of both NaV1.4 and CaV1.2, similar to H. suspectum venom. The ability of varanid venoms to bind to mammalian ion channels but not to the avian tissue preparation suggests prey-selective actions, as did the differential potency within the Heloderma venoms for avian versus mammalian pathophysiological targets. This study thus presents the detailed characterization of Heloderma venom ion channel neurotoxicity and offers the first evidence of varanid lizard venom neurotoxicity. In addition, the data not only provide information useful to understanding the clinical effects produced by envenomations, but also reveal their utility as physiological probes, and underscore the potential utility of neglected venomous lineages in the drug design and development pipeline.

ACS Style

James Dobson; Richard Harris; Christina Zdenek; Tam Huynh; Wayne Hodgson; Frank Bosmans; Rudy Fourmy; Aude Violette; Bryan Fry. The Dragon’s Paralysing Spell: Evidence of Sodium and Calcium Ion Channel Binding Neurotoxins in Helodermatid and Varanid Lizard Venoms. Toxins 2021, 13, 549 .

AMA Style

James Dobson, Richard Harris, Christina Zdenek, Tam Huynh, Wayne Hodgson, Frank Bosmans, Rudy Fourmy, Aude Violette, Bryan Fry. The Dragon’s Paralysing Spell: Evidence of Sodium and Calcium Ion Channel Binding Neurotoxins in Helodermatid and Varanid Lizard Venoms. Toxins. 2021; 13 (8):549.

Chicago/Turabian Style

James Dobson; Richard Harris; Christina Zdenek; Tam Huynh; Wayne Hodgson; Frank Bosmans; Rudy Fourmy; Aude Violette; Bryan Fry. 2021. "The Dragon’s Paralysing Spell: Evidence of Sodium and Calcium Ion Channel Binding Neurotoxins in Helodermatid and Varanid Lizard Venoms." Toxins 13, no. 8: 549.

Journal article
Published: 02 February 2021 in Toxins
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Snakes of the genera Pseudocerastes and Eristicophis (Viperidae: Viperinae) are known as the desert vipers due to their association with the arid environments of the Middle East. These species have received limited research attention and little is known about their venom or ecology. In this study, a comprehensive analysis of desert viper venoms was conducted by visualising the venom proteomes via gel electrophoresis and assessing the crude venoms for their cytotoxic, haemotoxic, and neurotoxic properties. Plasmas sourced from human, toad, and chicken were used as models to assess possible prey-linked venom activity. The venoms demonstrated substantial divergence in composition and bioactivity across all experiments. Pseudocerastes urarachnoides venom activated human coagulation factors X and prothrombin and demonstrated potent procoagulant activity in human, toad, and chicken plasmas, in stark contrast to the potent neurotoxic venom of P. fieldi. The venom of E. macmahonii also induced coagulation, though this did not appear to be via the activation of factor X or prothrombin. The coagulant properties of P. fieldi and P. persicus venoms varied among plasmas, demonstrating strong anticoagulant activity in the amphibian and human plasmas but no significant effect in that of bird. This is conjectured to reflect prey-specific toxin activity, though further ecological studies are required to confirm any dietary associations. This study reinforces the notion that phylogenetic relatedness of snakes cannot readily predict venom protein composition or function. The significant venom variation between these species raises serious concerns regarding antivenom paraspecificity. Future assessment of antivenom is crucial.

ACS Style

Bianca Op Den Brouw; Francisco Coimbra; Lachlan Bourke; Tam Huynh; Danielle Vlecken; Parviz Ghezellou; Jeroen Visser; James Dobson; Manuel Fernandez-Rojo; Maria Ikonomopoulou; Nicholas Casewell; Syed Ali; Behzad Fathinia; Wayne Hodgson; Bryan Fry. Extensive Variation in the Activities of Pseudocerastes and Eristicophis Viper Venoms Suggests Divergent Envenoming Strategies are Used for Prey Capture. Toxins 2021, 13, 112 .

AMA Style

Bianca Op Den Brouw, Francisco Coimbra, Lachlan Bourke, Tam Huynh, Danielle Vlecken, Parviz Ghezellou, Jeroen Visser, James Dobson, Manuel Fernandez-Rojo, Maria Ikonomopoulou, Nicholas Casewell, Syed Ali, Behzad Fathinia, Wayne Hodgson, Bryan Fry. Extensive Variation in the Activities of Pseudocerastes and Eristicophis Viper Venoms Suggests Divergent Envenoming Strategies are Used for Prey Capture. Toxins. 2021; 13 (2):112.

Chicago/Turabian Style

Bianca Op Den Brouw; Francisco Coimbra; Lachlan Bourke; Tam Huynh; Danielle Vlecken; Parviz Ghezellou; Jeroen Visser; James Dobson; Manuel Fernandez-Rojo; Maria Ikonomopoulou; Nicholas Casewell; Syed Ali; Behzad Fathinia; Wayne Hodgson; Bryan Fry. 2021. "Extensive Variation in the Activities of Pseudocerastes and Eristicophis Viper Venoms Suggests Divergent Envenoming Strategies are Used for Prey Capture." Toxins 13, no. 2: 112.

Journal article
Published: 30 January 2020 in Toxins
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Envenomations are complex medical emergencies that can have a range of symptoms and sequelae. The only specific, scientifically-validated treatment for envenomation is antivenom administration, which is designed to alleviate venom effects. A paucity of efficacy testing exists for numerous antivenoms worldwide, and understanding venom effects and venom potency can help identify antivenom improvement options. Some spider venoms can produce debilitating injuries or even death, yet have been largely neglected in venom and antivenom studies because of the low venom yields. Coagulation disturbances have been particularly under studied due to difficulties in working with blood and the coagulation cascade. These circumstances have resulted in suboptimal spider bite treatment for medically significant spider genera such as Loxosceles and Sicarius. This study identifies and quantifies the anticoagulant effects produced by venoms of three Loxoscles species (L. reclusa, L. boneti, and L. laeta) and that of Sicarius terrosus. We showed that the venoms of all studied species are able to cleave the fibrinogen Aα-chain with varying degrees of potency, with L. reclusa and S. terrosus venom cleaving the Aα-chain most rapidly. Thromboelastography analysis revealed that only L. reclusa venom is able to reduce clot strength, thereby presumably causing anticoagulant effects in the patient. Using the same thromboelastography assays, antivenom efficacy tests revealed that the commonly used Loxoscles-specific SMase D recombinant based antivenom failed to neutralize the anticoagulant effects produced by Loxosceles venom. This study demonstrates the fibrinogenolytic activity of Loxosceles and Sicarius venom and the neutralization failure of Loxosceles antivenom, thus providing impetus for antivenom improvement.

ACS Style

Dwin Grashof; Christina N. Zdenek; James S. Dobson; Nicholas J. Youngman; Francisco Coimbra; Melisa Benard-Valle; Alejandro Alagon; Bryan G. Fry. A Web of Coagulotoxicity: Failure of Antivenom to Neutralize the Destructive (Non-Clotting) Fibrinogenolytic Activity of Loxosceles and Sicarius Spider Venoms. Toxins 2020, 12, 91 .

AMA Style

Dwin Grashof, Christina N. Zdenek, James S. Dobson, Nicholas J. Youngman, Francisco Coimbra, Melisa Benard-Valle, Alejandro Alagon, Bryan G. Fry. A Web of Coagulotoxicity: Failure of Antivenom to Neutralize the Destructive (Non-Clotting) Fibrinogenolytic Activity of Loxosceles and Sicarius Spider Venoms. Toxins. 2020; 12 (2):91.

Chicago/Turabian Style

Dwin Grashof; Christina N. Zdenek; James S. Dobson; Nicholas J. Youngman; Francisco Coimbra; Melisa Benard-Valle; Alejandro Alagon; Bryan G. Fry. 2020. "A Web of Coagulotoxicity: Failure of Antivenom to Neutralize the Destructive (Non-Clotting) Fibrinogenolytic Activity of Loxosceles and Sicarius Spider Venoms." Toxins 12, no. 2: 91.

Journal article
Published: 16 October 2019 in Toxins
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The binding of compounds to nicotinic acetylcholine receptors is of great interest in biomedical research. However, progress in this area is hampered by the lack of a high-throughput, cost-effective, and taxonomically flexible platform. Current methods are low-throughput, consume large quantities of sample, or are taxonomically limited in which targets can be tested. We describe a novel assay which utilizes a label-free bio-layer interferometry technology, in combination with adapted mimotope peptides, in order to measure ligand binding to the orthosteric site of nicotinic acetylcholine receptor alpha-subunits of diverse organisms. We validated the method by testing the evolutionary patterns of a generalist feeding species (Acanthophis antarcticus), a fish specialist species (Aipysurus laevis), and a snake specialist species (Ophiophagus hannah) for comparative binding to the orthosteric site of fish, amphibian, lizard, snake, bird, marsupial, and rodent alpha-1 nicotinic acetylcholine receptors. Binding patterns corresponded with diet, with the Acanthophis antarcticus not showing bias towards any particular lineage, while Aipysurus laevis showed selectivity for fish, and Ophiophagus hannah a selectivity for snake. To validate the biodiscovery potential of this method, we screened Acanthophis antarcticus and Tropidolaemus wagleri venom for binding to human alpha-1, alpha-2, alpha-3, alpha-4, alpha-5, alpha-6, alpha-7, alpha-9, and alpha-10. While A. antarcticus was broadly potent, T. wagleri showed very strong but selective binding, specifically to the alpha-1 target which would be evolutionarily selected for, as well as the alpha-5 target which is of major interest for drug design and development. Thus, we have shown that our novel method is broadly applicable for studies including evolutionary patterns of venom diversification, predicting potential neurotoxic effects in human envenomed patients, and searches for novel ligands of interest for laboratory tools and in drug design and development.

ACS Style

Christina N. Zdenek; Richard J. Harris; Sanjaya Kuruppu; Nicholas Youngman; James S. Dobson; Jordan Debono; Muzaffar Khan; Ian Smith; Mike Yarski; David Harrich; Charlotte Sweeney; Nathan Dunstan; Luke Allen; Bryan G. Fry. A Taxon-Specific and High-Throughput Method for Measuring Ligand Binding to Nicotinic Acetylcholine Receptors. Toxins 2019, 11, 600 .

AMA Style

Christina N. Zdenek, Richard J. Harris, Sanjaya Kuruppu, Nicholas Youngman, James S. Dobson, Jordan Debono, Muzaffar Khan, Ian Smith, Mike Yarski, David Harrich, Charlotte Sweeney, Nathan Dunstan, Luke Allen, Bryan G. Fry. A Taxon-Specific and High-Throughput Method for Measuring Ligand Binding to Nicotinic Acetylcholine Receptors. Toxins. 2019; 11 (10):600.

Chicago/Turabian Style

Christina N. Zdenek; Richard J. Harris; Sanjaya Kuruppu; Nicholas Youngman; James S. Dobson; Jordan Debono; Muzaffar Khan; Ian Smith; Mike Yarski; David Harrich; Charlotte Sweeney; Nathan Dunstan; Luke Allen; Bryan G. Fry. 2019. "A Taxon-Specific and High-Throughput Method for Measuring Ligand Binding to Nicotinic Acetylcholine Receptors." Toxins 11, no. 10: 600.

Journal article
Published: 19 July 2019 in Toxins
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The genus Bitis comprises 17 snake species that inhabit Africa and the Arabian Peninsula. They are responsible for a significant proportion of snakebites in the region. The venoms of the two independent lineages of giant Bitis (B. arietans and again in the common ancestor of the clade consisting of B. gabonica, B. nasicornis, B. parviocula and B. rhinoceros) induce an array of debilitating effects including anticoagulation, hemorrhagic shock and cytotoxicity, whilst the dwarf species B. atropos is known to have strong neurotoxic effects. However, the venom effects of the other species within the genus have not been explored in detail. A series of coagulation assays were implemented to assess the coagulotoxic venom effects of fourteen species within the genus. This study identified procoagulant venom as the ancestral condition, retained only by the basal dwarf species B. worthingtoni, suggesting anticoagulant venom is a derived trait within the Bitis genus and has been secondarily amplified on at least four occasions. A wide range of anticoagulant mechanisms were identified, such as coagulant and destructive activities upon fibrinogen in both giant and dwarf Bitis and the action of inhibiting the prothrombinase complex, which is present in a clade of dwarf Bitis. Antivenom studies revealed that while the procoagulant effects of B. worthingtoni were poorly neutralized, and thus a cause for concern, the differential mechanisms of anticoagulation in other species were all well neutralized. Thus, this study concludes there is a wide range of coagulotoxic mechanisms which have evolved within the Bitis genus and that clinical management strategies are limited for the procoagulant effects of B. worthingtoni, but that anticoagulant effects of other species are readily treated by the South African polyvalent antivenom. These results therefore have direct, real-work implications for the treatment of envenomed patients.

ACS Style

Nicholas Youngman; Jordan Debono; James S. Dobson; Christina N. Zdenek; Richard J. Harris; Bianca Op Den Brouw; Francisco C. P. Coimbra; Arno Naude; Kristian Coster; Eric Sundman; Ralph Braun; Iwan Hendrikx; Bryan G. Fry. Venomous Landmines: Clinical Implications of Extreme Coagulotoxic Diversification and Differential Neutralization by Antivenom of Venoms within the Viperid Snake Genus Bitis. Toxins 2019, 11, 422 .

AMA Style

Nicholas Youngman, Jordan Debono, James S. Dobson, Christina N. Zdenek, Richard J. Harris, Bianca Op Den Brouw, Francisco C. P. Coimbra, Arno Naude, Kristian Coster, Eric Sundman, Ralph Braun, Iwan Hendrikx, Bryan G. Fry. Venomous Landmines: Clinical Implications of Extreme Coagulotoxic Diversification and Differential Neutralization by Antivenom of Venoms within the Viperid Snake Genus Bitis. Toxins. 2019; 11 (7):422.

Chicago/Turabian Style

Nicholas Youngman; Jordan Debono; James S. Dobson; Christina N. Zdenek; Richard J. Harris; Bianca Op Den Brouw; Francisco C. P. Coimbra; Arno Naude; Kristian Coster; Eric Sundman; Ralph Braun; Iwan Hendrikx; Bryan G. Fry. 2019. "Venomous Landmines: Clinical Implications of Extreme Coagulotoxic Diversification and Differential Neutralization by Antivenom of Venoms within the Viperid Snake Genus Bitis." Toxins 11, no. 7: 422.

Journal article
Published: 07 May 2019 in Toxins
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The functional activities of Anguimorpha lizard venoms have received less attention compared to serpent lineages. Bite victims of varanid lizards often report persistent bleeding exceeding that expected for the mechanical damage of the bite. Research to date has identified the blockage of platelet aggregation as one bleeding-inducing activity, and destructive cleavage of fibrinogen as another. However, the ability of the venoms to prevent clot formation has not been directly investigated. Using a thromboelastograph (TEG5000), clot strength was measured after incubating human fibrinogen with Heloderma and Varanus lizard venoms. Clot strengths were found to be highly variable, with the most potent effects produced by incubation with Varanus venoms from the Odatria and Euprepriosaurus clades. The most fibrinogenolytically active venoms belonged to arboreal species and therefore prey escape potential is likely a strong evolutionary selection pressure. The results are also consistent with reports of profusive bleeding from bites from other notably fibrinogenolytic species, such as V. giganteus. Our results provide evidence in favour of the predatory role of venom in varanid lizards, thus shedding light on the evolution of venom in reptiles and revealing potential new sources of bioactive molecules useful as lead compounds in drug design and development.

ACS Style

James S. Dobson; Christina N. Zdenek; Chris Hay; Aude Violette; Rudy Fourmy; Chip Cochran; Bryan G. Fry. Varanid Lizard Venoms Disrupt the Clotting Ability of Human Fibrinogen through Destructive Cleavage. Toxins 2019, 11, 255 .

AMA Style

James S. Dobson, Christina N. Zdenek, Chris Hay, Aude Violette, Rudy Fourmy, Chip Cochran, Bryan G. Fry. Varanid Lizard Venoms Disrupt the Clotting Ability of Human Fibrinogen through Destructive Cleavage. Toxins. 2019; 11 (5):255.

Chicago/Turabian Style

James S. Dobson; Christina N. Zdenek; Chris Hay; Aude Violette; Rudy Fourmy; Chip Cochran; Bryan G. Fry. 2019. "Varanid Lizard Venoms Disrupt the Clotting Ability of Human Fibrinogen through Destructive Cleavage." Toxins 11, no. 5: 255.

Journal article
Published: 04 December 2018 in Toxins
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Snakebite is a global tropical disease that has long had huge implications for human health and well-being. Despite its long-standing medical importance, it has been the most neglected of tropical diseases. Reflective of this is that many aspects of the pathology have been underinvestigated. Snakebite by species in the Elapidae family is typically characterised by neurotoxic effects that result in flaccid paralysis. Thus, while clinically significant disturbances to the coagulation cascade have been reported, the bulk of the research to date has focused upon neurotoxins. In order to fill the knowledge gap regarding the coagulotoxic effects of elapid snake venoms, we screened 30 African and Asian venoms across eight genera using in vitro anticoagulant assays to determine the relative inhibition of the coagulation function of thrombin and the inhibition of the formation of the prothrombinase complex through competitive binding to a nonenzymatic site on Factor Xa (FXa), thereby preventing FXa from binding to Factor Va (FVa). It was revealed that African spitting cobras were the only species that were potent inhibitors of either clotting factor, but with Factor Xa inhibited at 12 times the levels of thrombin inhibition. This is consistent with at least one death on record due to hemorrhage following African spitting cobra envenomation. To determine the efficacy of antivenom in neutralising the anticoagulant venom effects, for the African spitting cobras we repeated the same 8-point dilution series with the addition of antivenom and observed the shift in the area under the curve, which revealed that the antivenom performed extremely poorly against the coagulotoxic venom effects of all species. However, additional tests with the phospholipase A2 inhibitor LY315920 (trade name: varespladib) demonstrated a powerful neutralisation action against the coagulotoxic actions of the African spitting cobra venoms. Our research has important implications for the clinical treatment of cobra snakebites and also sheds light on the molecular mechanisms involved in coagulotoxicity within Naja. As the most coagulotoxic species are also those that produce characteristic extreme local tissue damage, future research should investigate potential synergistic actions between anticoagulant toxins and cytotoxins.

ACS Style

Mátyás A. Bittenbinder; Christina N. Zdenek; Bianca Op Den Brouw; Nicholas J. Youngman; James S. Dobson; Arno Naude; Freek J. Vonk; Bryan G. Fry. Coagulotoxic Cobras: Clinical Implications of Strong Anticoagulant Actions of African Spitting Naja Venoms That Are Not Neutralised by Antivenom but Are by LY315920 (Varespladib). Toxins 2018, 10, 516 .

AMA Style

Mátyás A. Bittenbinder, Christina N. Zdenek, Bianca Op Den Brouw, Nicholas J. Youngman, James S. Dobson, Arno Naude, Freek J. Vonk, Bryan G. Fry. Coagulotoxic Cobras: Clinical Implications of Strong Anticoagulant Actions of African Spitting Naja Venoms That Are Not Neutralised by Antivenom but Are by LY315920 (Varespladib). Toxins. 2018; 10 (12):516.

Chicago/Turabian Style

Mátyás A. Bittenbinder; Christina N. Zdenek; Bianca Op Den Brouw; Nicholas J. Youngman; James S. Dobson; Arno Naude; Freek J. Vonk; Bryan G. Fry. 2018. "Coagulotoxic Cobras: Clinical Implications of Strong Anticoagulant Actions of African Spitting Naja Venoms That Are Not Neutralised by Antivenom but Are by LY315920 (Varespladib)." Toxins 10, no. 12: 516.

Journal article
Published: 05 November 2018 in Toxins
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Assassin flies (Diptera: Asilidae) inject paralysing venom into insect prey during hunting, but their venoms are poorly characterised in comparison to those produced by spiders, scorpions, or hymenopteran insects. Here we investigated the composition of the venom of the giant Australian assassin fly Dolopus genitalis using a combination of insect microinjection assays, calcium imaging assays of mammalian sensory neurons, proteomics and transcriptomics. Injection of venom into blowflies (Lucilia cuprina) produced rapid contractile paralysis (PD50 at 1 min = 3.1 μg per fly) followed by death, and also caused immediate activation of mouse dorsal root ganglion neurons (at 50 ng/μL). These results are consistent with venom use for both prey capture and predator deterrence. Paragon searches of tandem mass spectra of venom against a translated thoracic gland RNA-Seq database identified 122 polypeptides present in the venom, including six linear and 21 disulfide-rich peptides. Some of these disulfide-rich peptides display sequence homology to peptide families independently recruited into other animal venoms, including inhibitor cystine knots, cystine-stabilised α/β defensins, Kazal peptides, and von Willebrand factors. Numerous enzymes are present in the venom, including 35 proteases of the S1 family, proteases of the S10, C1A, M12A, M14, and M17 families, and phosphatase, amylase, hydrolase, nuclease, and dehydrogenase-like proteins. These results highlight convergent molecular evolution between the assassin flies and other venomous animals, as well as the unique and rich molecular composition of assassin fly venom.

ACS Style

Andrew A. Walker; James Dobson; Jiayi Jin; Samuel D. Robinson; Volker Herzig; Irina Vetter; Glenn F. King; Bryan G. Fry. Buzz Kill: Function and Proteomic Composition of Venom from the Giant Assassin Fly Dolopus genitalis (Diptera: Asilidae). Toxins 2018, 10, 456 .

AMA Style

Andrew A. Walker, James Dobson, Jiayi Jin, Samuel D. Robinson, Volker Herzig, Irina Vetter, Glenn F. King, Bryan G. Fry. Buzz Kill: Function and Proteomic Composition of Venom from the Giant Assassin Fly Dolopus genitalis (Diptera: Asilidae). Toxins. 2018; 10 (11):456.

Chicago/Turabian Style

Andrew A. Walker; James Dobson; Jiayi Jin; Samuel D. Robinson; Volker Herzig; Irina Vetter; Glenn F. King; Bryan G. Fry. 2018. "Buzz Kill: Function and Proteomic Composition of Venom from the Giant Assassin Fly Dolopus genitalis (Diptera: Asilidae)." Toxins 10, no. 11: 456.

Journal article
Published: 11 October 2018 in Toxins
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Lancehead pit-vipers (Bothrops genus) are an extremely diverse and medically important group responsible for the greatest number of snakebite envenomations and deaths in South America. Bothrops atrox (common lancehead), responsible for majority of snakebites and related deaths within the Brazilian Amazon, is a highly adaptable and widely distributed species, whose venom variability has been related to several factors, including geographical distribution and habitat type. This study examined venoms from four B. atrox populations (Belterra and Santarém, PA; Pres. Figueiredo, AM and São Bento, MA), and two additional Bothrops species (B. jararaca and B. neuwiedi) from Southeastern region for their coagulotoxic effects upon different plasmas (human, amphibian, and avian). The results revealed inter– and intraspecific variations in coagulotoxicity, including distinct activities between the three plasmas, with variations in the latter two linked to ecological niche occupied by the snakes. Also examined were the correlated biochemical mechanisms of venom action. Significant variation in the relative reliance upon the cofactors calcium and phospholipid were revealed, and the relative dependency did not significantly correlate with potency. Relative levels of Factor X or prothrombin activating toxins correlated with prey type and prey escape potential. The antivenom was shown to perform better in neutralising prothrombin activation activity than neutralising Factor X activation activity. Thus, the data reveal new information regarding the evolutionary selection pressures shaping snake venom evolution, while also having significant implications for the treatment of the envenomed patient. These results are, therefore, an intersection between evolutionary biology and clinical medicine.

ACS Style

Leijiane F. Sousa; Christina N. Zdenek; James S. Dobson; Bianca Op Den Brouw; Francisco C. P. Coimbra; Amber Gillett; Tiago H. M. Del-Rei; Hipócrates De M. Chalkidis; Sávio Sant’Anna; Marisa M. Teixeira-Da-Rocha; Kathleen Grego; Silvia R. Travaglia Cardoso; Ana M. Moura Da Silva; Bryan G. Fry. Coagulotoxicity of Bothrops (Lancehead Pit-Vipers) Venoms from Brazil: Differential Biochemistry and Antivenom Efficacy Resulting from Prey-Driven Venom Variation. Toxins 2018, 10, 411 .

AMA Style

Leijiane F. Sousa, Christina N. Zdenek, James S. Dobson, Bianca Op Den Brouw, Francisco C. P. Coimbra, Amber Gillett, Tiago H. M. Del-Rei, Hipócrates De M. Chalkidis, Sávio Sant’Anna, Marisa M. Teixeira-Da-Rocha, Kathleen Grego, Silvia R. Travaglia Cardoso, Ana M. Moura Da Silva, Bryan G. Fry. Coagulotoxicity of Bothrops (Lancehead Pit-Vipers) Venoms from Brazil: Differential Biochemistry and Antivenom Efficacy Resulting from Prey-Driven Venom Variation. Toxins. 2018; 10 (10):411.

Chicago/Turabian Style

Leijiane F. Sousa; Christina N. Zdenek; James S. Dobson; Bianca Op Den Brouw; Francisco C. P. Coimbra; Amber Gillett; Tiago H. M. Del-Rei; Hipócrates De M. Chalkidis; Sávio Sant’Anna; Marisa M. Teixeira-Da-Rocha; Kathleen Grego; Silvia R. Travaglia Cardoso; Ana M. Moura Da Silva; Bryan G. Fry. 2018. "Coagulotoxicity of Bothrops (Lancehead Pit-Vipers) Venoms from Brazil: Differential Biochemistry and Antivenom Efficacy Resulting from Prey-Driven Venom Variation." Toxins 10, no. 10: 411.

Comparative study
Published: 19 May 2017 in Toxins
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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.

ACS Style

Jordan Debono; James Dobson; Nicholas R. Casewell; Anthony Romilio; Bin Li; Nyoman Kurniawan; Karine Mardon; Vera Weisbecker; Amanda Nouwens; Hang Fai Kwok; Bryan G. Fry. Coagulating Colubrids: Evolutionary, Pathophysiological and Biodiscovery Implications of Venom Variations between Boomslang (Dispholidus typus) and Twig Snake (Thelotornis mossambicanus). Toxins 2017, 9, 171 .

AMA Style

Jordan Debono, James Dobson, Nicholas R. Casewell, Anthony Romilio, Bin Li, Nyoman Kurniawan, Karine Mardon, Vera Weisbecker, Amanda Nouwens, Hang Fai Kwok, Bryan G. Fry. Coagulating Colubrids: Evolutionary, Pathophysiological and Biodiscovery Implications of Venom Variations between Boomslang (Dispholidus typus) and Twig Snake (Thelotornis mossambicanus). Toxins. 2017; 9 (5):171.

Chicago/Turabian Style

Jordan Debono; James Dobson; Nicholas R. Casewell; Anthony Romilio; Bin Li; Nyoman Kurniawan; Karine Mardon; Vera Weisbecker; Amanda Nouwens; Hang Fai Kwok; Bryan G. Fry. 2017. "Coagulating Colubrids: Evolutionary, Pathophysiological and Biodiscovery Implications of Venom Variations between Boomslang (Dispholidus typus) and Twig Snake (Thelotornis mossambicanus)." Toxins 9, no. 5: 171.