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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.
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 StyleJames 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 StyleJames 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.
The reef stonefish (Synanceia verrucosa) is a venomous fish which causes excruciatingly painful envenomations. While some research on the pathophysiology and functions of the venom have been conducted, there are still some gaps in the understanding of the venom effects due to the extreme lability of fish venom toxins and the lack of available testing platforms. Here we set out to assess new functions of the venom whilst also attempting to address some unclear pathophysiological effects from previous literature. Utilising a biolayer interferometry assay, our results highlight that the venom binds to the orthosteric site of the α-1 nicotinic acetylcholine receptor as well as the domain IV of voltage-gated Ca2+ (CaV1.2) channel mimotopes. Both these results add some clarity to the previously ambiguous literature. We further assessed the coagulotoxic effects of the venom using thromboelastography and Stago STA-R Max coagulation analyser assays. We reveal that the venom produced anticoagulant activity and significantly delayed time until clot formation of recalcified human plasma which is likely through the degradation of phospholipids. There was a difference between fresh and lyophilised venom activity toward the nicotinic acetylcholine receptor mimotopes and coagulation assays, whilst no difference was observed in the activity toward the domain IV of CaV1.2 mimotopes. This research adds further insights into the neglected area of fish venom whilst also highlighting the extreme labile nature of fish venom toxins.
Richard J. Harris; Nicholas J. Youngman; Weili Chan; Frank Bosmans; Karen L. Cheney; Bryan G. Fry. Getting stoned: Characterisation of the coagulotoxic and neurotoxic effects of reef stonefish (Synanceia verrucosa) venom. Toxicology Letters 2021, 346, 16 -22.
AMA StyleRichard J. Harris, Nicholas J. Youngman, Weili Chan, Frank Bosmans, Karen L. Cheney, Bryan G. Fry. Getting stoned: Characterisation of the coagulotoxic and neurotoxic effects of reef stonefish (Synanceia verrucosa) venom. Toxicology Letters. 2021; 346 ():16-22.
Chicago/Turabian StyleRichard J. Harris; Nicholas J. Youngman; Weili Chan; Frank Bosmans; Karen L. Cheney; Bryan G. Fry. 2021. "Getting stoned: Characterisation of the coagulotoxic and neurotoxic effects of reef stonefish (Synanceia verrucosa) venom." Toxicology Letters 346, no. : 16-22.
The evolution of venom resistance through coevolutionary chemical arms races has arisen multiple times throughout animalia. Prior documentation of resistance to snake venom α-neurotoxins consists of the N-glycosylation motif or the hypothesized introduction of arginine at positions 187 at the α-1 nicotinic acetylcholine receptor orthosteric site. However, no further studies have investigated the possibility of other potential forms of resistance. Using a biolayer interferometry assay, we first confirm that the previously hypothesized resistance conferred by arginine at position 187 in the honey badger does reduce binding to α-neurotoxins, which has never been functionally tested. We further discovered a novel form of α-neurotoxin resistance conferred by charge reversal mutations, whereby a negatively charged amino acid is replaced by the positively charged amino acid lysine. As venom α-neurotoxins have evolved strong positive charges on their surface to facilitate binding to the negatively charged α-1 orthosteric site, these mutations result in a positive charge/positive charge interaction electrostatically repelling the α-neurotoxins. Such a novel mechanism for resistance has gone completely undiscovered, yet this form of resistance has convergently evolved at least 10 times within snakes. These coevolutionary innovations seem to have arisen through convergent phenotypes to ultimately evolve a similar biophysical mechanism of resistance across snakes.
Richard J. Harris; Bryan G. Fry. Electrostatic resistance to alpha-neurotoxins conferred by charge reversal mutations in nicotinic acetylcholine receptors. Proceedings of the Royal Society of London. Series B: Biological Sciences 2021, 288, 20202703 .
AMA StyleRichard J. Harris, Bryan G. Fry. Electrostatic resistance to alpha-neurotoxins conferred by charge reversal mutations in nicotinic acetylcholine receptors. Proceedings of the Royal Society of London. Series B: Biological Sciences. 2021; 288 (1942):20202703.
Chicago/Turabian StyleRichard J. Harris; Bryan G. Fry. 2021. "Electrostatic resistance to alpha-neurotoxins conferred by charge reversal mutations in nicotinic acetylcholine receptors." Proceedings of the Royal Society of London. Series B: Biological Sciences 288, no. 1942: 20202703.
The evolution of an aquatic lifestyle from land dwelling venomous elapids is a radical ecological modification, bringing about many evolutionary changes from morphology to diet. Diet is an important ecological facet which can play a key role in regulating functional traits such as venom composition and prey-specific targeting of venom. In addition to predating upon novel prey (e.g., fish, fish eggs and invertebrates), the venoms of aquatic elapids also face the challenge of increased prey-escape potential in the aquatic environment. Thus, despite the independent radiation into an aquatic niche on four separate occasions, the venoms of aquatic elapids are evolving under convergent selection pressures. Utilising a biolayer interferometry binding assay, this study set out to elucidate whether crude venoms from representative aquatic elapids were target-specific to the orthosteric site of postsynaptic nicotinic acetylcholine receptor mimotopes of fish compared to other terrestrial prey types. Representatives of the four aquatic lineages were: aquatic coral snakes representative was Micrurus surinamensis;, sea kraits representative was Laticauda colubrina; sea snakes representatives were two Aipysurus spp. and eight Hydrophis spp; and water cobras representative was Naja annulata. No prey-specific differences in crude venom binding were observed from any species tested, except for Aipysurus laevis, which showed slight evidence of prey-potency differences. For Hydrophis caerulescens, H. peronii, H. schistosus and M. surinamensis, there was a lack of binding to the orthosteric site of any target lineage. Subsequent testing on the in vitro chick-biventer cervicis muscle preparation suggested that, while the venoms of these species bound postsynaptically, they bound to allosteric sites rather than orthosteric. Allosteric binding is potentially a weaker but faster-acting form of neurotoxicity and we hypothesise that the switch to allosteric binding is likely due to selection pressures related to prey-escape potential. This research has potentially opened up the possibility of a new functional class of toxins which have never been assessed previously while shedding light on the selection pressures shaping venom evolution.
Richard J. Harris; Nicholas J. Youngman; Christina N. Zdenek; Tam M. Huynh; Amanda Nouwens; Wayne C. Hodgson; David Harrich; Nathan Dunstan; José A. Portes-Junior; Bryan G. Fry. Assessing the Binding of Venoms from Aquatic Elapids to the Nicotinic Acetylcholine Receptor Orthosteric Site of Different Prey Models. International Journal of Molecular Sciences 2020, 21, 7377 .
AMA StyleRichard J. Harris, Nicholas J. Youngman, Christina N. Zdenek, Tam M. Huynh, Amanda Nouwens, Wayne C. Hodgson, David Harrich, Nathan Dunstan, José A. Portes-Junior, Bryan G. Fry. Assessing the Binding of Venoms from Aquatic Elapids to the Nicotinic Acetylcholine Receptor Orthosteric Site of Different Prey Models. International Journal of Molecular Sciences. 2020; 21 (19):7377.
Chicago/Turabian StyleRichard J. Harris; Nicholas J. Youngman; Christina N. Zdenek; Tam M. Huynh; Amanda Nouwens; Wayne C. Hodgson; David Harrich; Nathan Dunstan; José A. Portes-Junior; Bryan G. Fry. 2020. "Assessing the Binding of Venoms from Aquatic Elapids to the Nicotinic Acetylcholine Receptor Orthosteric Site of Different Prey Models." International Journal of Molecular Sciences 21, no. 19: 7377.
Contralaterally positioned maxillary (upper jaw) venom glands in snakes are mechanically independent, being able to discharge venom from either gland separately. This has led some studies to test venom function and composition of each contralaterally positioned venom gland to investigate any differences. However, the data on the subject to-date derives from limited sample sizes, appearing somewhat contradictory, and thus still remains inconclusive. Here, we tested samples obtained from the left and right venom glands of four N. siamensis specimens for their relative binding to the orthosteric site of amphibian, lizard, snake, bird, and rodent alpha-1 nicotinic acetylcholine receptors. We also show the relative proteomic patterns displayed by reversed phase liquid chromatography – mass spectrometry. Our results indicate that three of the venom gland sets showed no difference in both functional binding and composition, whilst one venom gland set showed a slight difference in functional binding (but not in specificity patterns between prey types) or venom composition. We hypothesise that these differences in functional binding may be due to one gland having previously ejected venom at some time prior to venom extraction, whilst its contralateral counterpart did not. This might cause the differential rate of toxin replenishment to be unequal between glands, thus instigating the difference in potency, likely due to uneven toxin proportions between glands at the time of venom extraction. These results demonstrate that the separate venom producing glands in snakes remain under the same genetic control elements and produce identical venom components.
Richard J. Harris; Christina N. Zdenek; Amanda Nouwens; Charlotte Sweeney; Nathan Dunstan; Bryan G. Fry. A symmetry or asymmetry: Functional and compositional comparison of venom from the left and right glands of the Indochinese spitting cobra (Naja siamensis). Toxicon: X 2020, 7, 100050 .
AMA StyleRichard J. Harris, Christina N. Zdenek, Amanda Nouwens, Charlotte Sweeney, Nathan Dunstan, Bryan G. Fry. A symmetry or asymmetry: Functional and compositional comparison of venom from the left and right glands of the Indochinese spitting cobra (Naja siamensis). Toxicon: X. 2020; 7 ():100050.
Chicago/Turabian StyleRichard J. Harris; Christina N. Zdenek; Amanda Nouwens; Charlotte Sweeney; Nathan Dunstan; Bryan G. Fry. 2020. "A symmetry or asymmetry: Functional and compositional comparison of venom from the left and right glands of the Indochinese spitting cobra (Naja siamensis)." Toxicon: X 7, no. : 100050.
Ecological variability among closely related species provides an opportunity for evolutionary comparative studies. Therefore, to investigate the origin and evolution of neurotoxicity in Asian viperid snakes, we tested the venoms of Azemiops feae, Calloselasma rhodostoma, Deinagkistrodon acutus, Tropidolaeums subannulatus, and T. wagleri for their relative specificity and potency upon the amphibian, lizard, bird, rodent, and human α-1 (neuromuscular) nicotinic acetylcholine receptors. We utilised a biolayer interferometry assay to test the binding affinity of these pit viper venoms to orthosteric mimotopes of nicotinic acetylcholine receptors binding region from a diversity of potential prey types. The Tropidolaemus venoms were much more potent than the other species tested, which is consistent with the greater prey escape potential in arboreal niches. Intriguingly, the venom of C. rhodostoma showed neurotoxic binding to the α-1 mimotopes, a feature not known previously for this species. The lack of prior knowledge of neurotoxicity in this species is consistent with our results due to the bias in rodent studies and human bite reports, whilst this venom had a greater binding affinity toward amphibian and diapsid α-1 targets. The other large terrestrial species, D. acutus, did not display any meaningful levels of neurotoxicity. These results demonstrate that whilst small peptide neurotoxins are a basal trait of these snakes, it has been independently amplified on two separate occasions, once in Azemiops and again in Tropidolaemus, and with Calloselasma representing a third possible amplification of this trait. These results also point to broader sources of novel neuroactive peptides with the potential for use as lead compounds in drug design and discovery.
Richard J. Harris; Christina N. Zdenek; Jordan Debono; David Harrich; Bryan G. Fry. Evolutionary Interpretations of Nicotinic Acetylcholine Receptor Targeting Venom Effects by a Clade of Asian Viperidae Snakes. Neurotoxicity Research 2020, 38, 312 -318.
AMA StyleRichard J. Harris, Christina N. Zdenek, Jordan Debono, David Harrich, Bryan G. Fry. Evolutionary Interpretations of Nicotinic Acetylcholine Receptor Targeting Venom Effects by a Clade of Asian Viperidae Snakes. Neurotoxicity Research. 2020; 38 (2):312-318.
Chicago/Turabian StyleRichard J. Harris; Christina N. Zdenek; Jordan Debono; David Harrich; Bryan G. Fry. 2020. "Evolutionary Interpretations of Nicotinic Acetylcholine Receptor Targeting Venom Effects by a Clade of Asian Viperidae Snakes." Neurotoxicity Research 38, no. 2: 312-318.
Prey-selective venoms and toxins have been documented across only a few species of snakes. The lack of research in this area has been due to the absence of suitably flexible testing platforms. In order to test more species for prey specificity of their venom, we used an innovative taxonomically flexible, high-throughput biolayer interferometry approach to ascertain the relative binding of 29 α-neurotoxic venoms from African and Asian elapid representatives (26 Naja spp., Aspidelaps scutatus, Elapsoidea boulengeri, and four locales of Ophiophagus hannah) to the alpha-1 nicotinic acetylcholine receptor orthosteric (active) site for amphibian, lizard, snake, bird, and rodent targets. Our results detected prey-selective, intraspecific, and geographical differences of α-neurotoxic binding. The results also suggest that crude venom that shows prey selectivity is likely driven by the proportions of prey-specific α-neurotoxins with differential selectivity within the crude venom. Our results also suggest that since the α-neurotoxic prey targeting does not always account for the full dietary breadth of a species, other toxin classes with a different pathophysiological function likely play an equally important role in prey immobilisation of the crude venom depending on the prey type envenomated. The use of this innovative and taxonomically flexible diverse assay in functional venom testing can be key in attempting to understanding the evolution and ecology of α-neurotoxic snake venoms, as well as opening up biochemical and pharmacological avenues to explore other venom effects.
Richard J. Harris; Christina N. Zdenek; David Harrich; Nathaniel Frank; Bryan G. Fry. An Appetite for Destruction: Detecting Prey-Selective Binding of α-Neurotoxins in the Venom of Afro-Asian Elapids. Toxins 2020, 12, 205 .
AMA StyleRichard J. Harris, Christina N. Zdenek, David Harrich, Nathaniel Frank, Bryan G. Fry. An Appetite for Destruction: Detecting Prey-Selective Binding of α-Neurotoxins in the Venom of Afro-Asian Elapids. Toxins. 2020; 12 (3):205.
Chicago/Turabian StyleRichard J. Harris; Christina N. Zdenek; David Harrich; Nathaniel Frank; Bryan G. Fry. 2020. "An Appetite for Destruction: Detecting Prey-Selective Binding of α-Neurotoxins in the Venom of Afro-Asian Elapids." Toxins 12, no. 3: 205.
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.
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 StyleChristina 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 StyleChristina 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.
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.
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 StyleNicholas 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 StyleNicholas 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.
Research on venomous animals has mainly focused on the molecular, biochemical, and pharmacological aspects of venom toxins. However, it is the relatively neglected broader study of evolutionary ecology that is crucial for understanding the biological relevance of venom systems. As fish have convergently evolved venom systems multiple times, it makes them ideal organisms to investigate the evolutionary ecology of venom on a broader scale. This review outlines what is known about how fish venom systems evolved as a result of natural enemy interactions and about the ecological consequences of evolving a venom system. This review will show how research on the evolutionary ecology of venom in fish can aid in understanding the evolutionary ecology of animal venoms more generally. Further, understanding these broad ecological questions can shed more light on the other areas of toxinology, with applications across multiple disciplinary fields.
Richard J. Harris; Ronald A. Jenner. Evolutionary Ecology of Fish Venom: Adaptations and Consequences of Evolving a Venom System. Toxins 2019, 11, 60 .
AMA StyleRichard J. Harris, Ronald A. Jenner. Evolutionary Ecology of Fish Venom: Adaptations and Consequences of Evolving a Venom System. Toxins. 2019; 11 (2):60.
Chicago/Turabian StyleRichard J. Harris; Ronald A. Jenner. 2019. "Evolutionary Ecology of Fish Venom: Adaptations and Consequences of Evolving a Venom System." Toxins 11, no. 2: 60.
Animals that specialise in blood feeding have particular challenges in obtaining their meal, whereby they impair blood hemostasis by promoting anticoagulation and vasodilation in order to facilitate feeding. These convergent selection pressures have been studied in a number of lineages, ranging from fleas to leeches. However, the vampire bat (Desmondus rotundus) is unstudied in regards to potential vasodilatory mechanisms of their feeding secretions (which are a type of venom). This is despite the intense investigations of their anticoagulant properties which have demonstrated that D. rotundus venom contains strong anticoagulant and proteolytic activities which delay the formation of blood clots and interfere with the blood coagulation cascade. In this study, we identified and tested a compound from D. rotundus venom that is similar in size and amino acid sequence to human calcitonin gene-related peptide (CGRP) which has potent vasodilatory properties. We found that the vampire bat-derived form of CGRP (i.e., vCGRP) selectively caused endothelium-independent relaxation of pre-contracted rat small mesenteric arteries. The vasorelaxant efficacy and potency of vCGRP were similar to that of CGRP, in activating CGRP receptors and Kv channels to relax arteriole smooth muscle, which would facilitate blood meal feeding by promoting continual blood flow. Our results provide, for the first time, a detailed investigation into the identification and function of a vasodilatory peptide found in D. rotundus venom, which provides a basis in understanding the convergent pathways and selectivity of hematophagous venoms. These unique peptides also show excellent drug design and development potential, thus highlighting the social and economic value of venomous animals.
Rahini Kakumanu; Wayne C. Hodgson; Ravina Ravi; Alejandro Alagon; Richard J. Harris; Andreas Brust; Paul F. Alewood; Barbara K. Kemp-Harper; Bryan G. Fry. Vampire Venom: Vasodilatory Mechanisms of Vampire Bat (Desmodus rotundus) Blood Feeding. Toxins 2019, 11, 26 .
AMA StyleRahini Kakumanu, Wayne C. Hodgson, Ravina Ravi, Alejandro Alagon, Richard J. Harris, Andreas Brust, Paul F. Alewood, Barbara K. Kemp-Harper, Bryan G. Fry. Vampire Venom: Vasodilatory Mechanisms of Vampire Bat (Desmodus rotundus) Blood Feeding. Toxins. 2019; 11 (1):26.
Chicago/Turabian StyleRahini Kakumanu; Wayne C. Hodgson; Ravina Ravi; Alejandro Alagon; Richard J. Harris; Andreas Brust; Paul F. Alewood; Barbara K. Kemp-Harper; Bryan G. Fry. 2019. "Vampire Venom: Vasodilatory Mechanisms of Vampire Bat (Desmodus rotundus) Blood Feeding." Toxins 11, no. 1: 26.
Toxic weaponry in the form of venom and poison has evolved in most groups of animals, including all four major lineages of tetrapods. Moreover, the evolution of such traits has been linked to several key aspects of the biology of toxic animals including life-history and diversification. Despite this, attempts to investigate the macroevolutionary patterns underlying such weaponry are lacking. In this study we analyse patterns of venom and poison evolution across reptiles, amphibians, mammals, and birds using a suite of phylogenetic comparative methods. We find that each major lineage has a characteristic pattern of trait evolution, but mammals and reptiles evolve under a surprisingly similar regime, whilst that of amphibians appears to be particularly distinct and highly contrasting compared to other groups. Our results also suggest that the mechanism of toxin acquisition may be an important distinction in such evolutionary patterns; the evolution of biosynthesis is far less dynamic than that of sequestration of toxins from the diet. Finally, contrary to the situation in amphibians, other tetrapod groups show an association between the evolution of toxic weaponry and higher diversification rates. Taken together, our study provides the first broad-scale analysis of macroevolutionary patterns of venom and poison throughout tetrapods.
Richard J. Harris; Kevin Arbuckle. Tempo and Mode of the Evolution of Venom and Poison in Tetrapods. Toxins 2016, 8, 193 .
AMA StyleRichard J. Harris, Kevin Arbuckle. Tempo and Mode of the Evolution of Venom and Poison in Tetrapods. Toxins. 2016; 8 (7):193.
Chicago/Turabian StyleRichard J. Harris; Kevin Arbuckle. 2016. "Tempo and Mode of the Evolution of Venom and Poison in Tetrapods." Toxins 8, no. 7: 193.