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Mud in the blood: Novel potent anticoagulant coagulotoxicity in the venoms of the Australian elapid snake genus Denisonia (mud adders) and relative antivenom efficacy.
Toxicol Lett 2019; 302:1-6TL

Abstract

Due to their potent coagulotoxicity, Australian elapid venoms are unique relative to non-Australian members of the Elapidae snake family. The majority of Australian elapids possess potent procoagulant venom, while only a few species have been identified as possessing anticoagulant venoms. The majority of research to-date has concentrated on large species with range distributions overlapping major city centres, such as brown snakes (Pseudonaja spp.) and taipans (Oxyuranus spp.). We investigated the venom from the poorly studied genus Denisonia and documented anticoagulant activities that were differentially potent on amphibian, avian, and human plasmas. Both species were potently anticoagulant upon amphibian plasma, consistent with these snakes preying upon frogs as their primary food source. While D. devisi was only relatively weakly active on avian and human plasma, D. maculata was potently anticoagulant to amphibian, avian, and human plasma. The mechanism of anticoagulant action was determined to be the inhibition of prothrombin activation by Factor Xa by blocking the formation of the prothrombinase complex. Fractionation of D. maculata venom followed by MS sequencing revealed that the toxins responsible were Group I phospholipase A2. As no antivenom is produced for this species or its near relatives, we examined the ability of Seqirus Australian snake polyvalent antivenom to neutralise the anticoagulant effects, with this antivenom shown to be effective. These results contribute to the body of knowledge regarding adaptive evolution of venom, revealing a unique taxon-specific anticoagulant effect for D. devisi venom. These results also reveal the potential effects and mechanisms behind envenomation by the potently acting D. maculata venom on human plasma, while the discovery of the efficacy of an available antivenom provides information crucial to the design of snakebite management strategies.

Authors+Show Affiliations

Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD, 4072, Australia.Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD, 4072, Australia.Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD, 4072, Australia.Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD, 4072, Australia.FaunaVet Wildlife Consultancy, Glass House Mountains, QLD, 4518, Australia.Centre of Advanced Imaging & Centre for Microscopy and Microanalysis, University of Queensland, St Lucia, QLD, 4072, Australia.Venom Supplies, Tanunda, South Australia, Australia.Venom Supplies, Tanunda, South Australia, Australia.Footprints Environmental Consultants Pty Ltd, P.O. Box 246, Bribie Island, QLD, 4507, Australia.Footprints Environmental Consultants Pty Ltd, P.O. Box 246, Bribie Island, QLD, 4507, Australia.FaunaVet Wildlife Consultancy, Glass House Mountains, QLD, 4518, Australia. Electronic address: bgfry@uq.edu.au.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30502385

Citation

Youngman, Nicholas J., et al. "Mud in the Blood: Novel Potent Anticoagulant Coagulotoxicity in the Venoms of the Australian Elapid Snake Genus Denisonia (mud Adders) and Relative Antivenom Efficacy." Toxicology Letters, vol. 302, 2019, pp. 1-6.
Youngman NJ, Zdenek CN, Dobson JS, et al. Mud in the blood: Novel potent anticoagulant coagulotoxicity in the venoms of the Australian elapid snake genus Denisonia (mud adders) and relative antivenom efficacy. Toxicol Lett. 2019;302:1-6.
Youngman, N. J., Zdenek, C. N., Dobson, J. S., Bittenbinder, M. A., Gillett, A., Hamilton, B., ... Fry, B. G. (2019). Mud in the blood: Novel potent anticoagulant coagulotoxicity in the venoms of the Australian elapid snake genus Denisonia (mud adders) and relative antivenom efficacy. Toxicology Letters, 302, pp. 1-6. doi:10.1016/j.toxlet.2018.11.015.
Youngman NJ, et al. Mud in the Blood: Novel Potent Anticoagulant Coagulotoxicity in the Venoms of the Australian Elapid Snake Genus Denisonia (mud Adders) and Relative Antivenom Efficacy. Toxicol Lett. 2019 Mar 1;302:1-6. PubMed PMID: 30502385.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mud in the blood: Novel potent anticoagulant coagulotoxicity in the venoms of the Australian elapid snake genus Denisonia (mud adders) and relative antivenom efficacy. AU - Youngman,Nicholas J, AU - Zdenek,Christina N, AU - Dobson,James S, AU - Bittenbinder,Matyas A, AU - Gillett,Amber, AU - Hamilton,Brett, AU - Dunstan,Nathan, AU - Allen,Luke, AU - Veary,Andrew, AU - Veary,Elle, AU - Fry,Bryan G, Y1 - 2018/11/28/ PY - 2018/08/29/received PY - 2018/11/23/revised PY - 2018/11/26/accepted PY - 2018/12/7/pubmed PY - 2019/2/27/medline PY - 2018/12/4/entrez KW - Anticoagulation KW - Antivenom KW - Coagulation KW - Denisonia KW - Prothrombinase KW - Venom SP - 1 EP - 6 JF - Toxicology letters JO - Toxicol. Lett. VL - 302 N2 - Due to their potent coagulotoxicity, Australian elapid venoms are unique relative to non-Australian members of the Elapidae snake family. The majority of Australian elapids possess potent procoagulant venom, while only a few species have been identified as possessing anticoagulant venoms. The majority of research to-date has concentrated on large species with range distributions overlapping major city centres, such as brown snakes (Pseudonaja spp.) and taipans (Oxyuranus spp.). We investigated the venom from the poorly studied genus Denisonia and documented anticoagulant activities that were differentially potent on amphibian, avian, and human plasmas. Both species were potently anticoagulant upon amphibian plasma, consistent with these snakes preying upon frogs as their primary food source. While D. devisi was only relatively weakly active on avian and human plasma, D. maculata was potently anticoagulant to amphibian, avian, and human plasma. The mechanism of anticoagulant action was determined to be the inhibition of prothrombin activation by Factor Xa by blocking the formation of the prothrombinase complex. Fractionation of D. maculata venom followed by MS sequencing revealed that the toxins responsible were Group I phospholipase A2. As no antivenom is produced for this species or its near relatives, we examined the ability of Seqirus Australian snake polyvalent antivenom to neutralise the anticoagulant effects, with this antivenom shown to be effective. These results contribute to the body of knowledge regarding adaptive evolution of venom, revealing a unique taxon-specific anticoagulant effect for D. devisi venom. These results also reveal the potential effects and mechanisms behind envenomation by the potently acting D. maculata venom on human plasma, while the discovery of the efficacy of an available antivenom provides information crucial to the design of snakebite management strategies. SN - 1879-3169 UR - https://www.unboundmedicine.com/medline/citation/30502385/Mud_in_the_blood:_Novel_potent_anticoagulant_coagulotoxicity_in_the_venoms_of_the_Australian_elapid_snake_genus_Denisonia_(mud_adders)_and_relative_antivenom_efficacy L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-4274(18)31829-0 DB - PRIME DP - Unbound Medicine ER -