Bryan G Fry
My Adaptive Biotoxicology Lab specialises in reconstructing the evolutionary history of venomous animals, both of the toxins themselves as well as the glands. This not only sheds light on the evolutionary processes that shape venom evolution but also provides an integrated search strategy for biodiscovery.
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The snake genera Atropoides, Cerrophidion, and Metlapilcoaltus form a clade of Neotropical pit vipers distributed across Mexico and Central America. This study evaluated the myotoxic and neurotoxic effects of nine species of Atropoides, Cerrophidion and Metlapilcoatlus, and the neutralising efficacy of the ICP antivenom from Costa Rica against these effects, in the chick biventer cervicis nerve-muscle preparation. Given the prominence of PLA2s within the venom proteomes of these species, we also aimed to determine the neutralising potency of the PLA2 inhibitor, varespladib.
Results:
All venoms showed myotoxic, and potential neurotoxic effects, with differential intra-genera and inter-genera potency. This variation was also seen in the antivenoms ability to neutralise the muscle damaging pathophysiological effects observed. Variation was also seen in the relative response to the PLA2-inhibitor varespladib. While the myotoxic effects of M. mexicanus and M. nummifer venoms were effectively neutralised by varespladib, indicating myotoxicity is PLA2 mediated, those of C. godmani and M. olmec venoms were not, revealing that the myotoxicity is driven by non-PLA2 toxin types.
Conclusions:
This study characterises the myotoxic and neurotoxic venom activity, as well as neutralisation of venom effects from the Atropoides, Cerrophidion, and Metlapilcoatlus clade of American Crotalids. Our findings contribute significant clinical and evolutionary knowledge to a clade of poorly researched snakes. In addition, these results provide a platform for future research into the reciprocal interaction between ecological niche specialisation and venom evolution, as well as highlighting the need to test purified toxins to accurately evaluate the potential effects observed in these venoms.
V. a. meridionalis venoms produced procoagulant effects, the effects produced by neonate venom were more potent. Consistent with this, neonate venom was a stronger activator of blood-clotting zymogens, converting them into their active forms, with a rank order of Factor X >> Factor VII> Factor XII. Conversely, the less potent adult venom had a rank order of FXII marginally more activated than Factor VII, and both much more so than Factor X. This adds to the growing body of evidence that activation of factors besides FII (prothrombin) and FX are significant variables in reptile venom-induced coagulopathy. Although all three examined antivenoms displayed effective
neutralization of both neonate and adult V. a. meridionalis venoms, they generally showed higher efficacy on adult venom than on neonate venom. The ranking of antivenom efficacy against neonate venom, from the most effective to the least effective, were Viperfav, Inoserp Europe, ViperaTAb; for
adult venom, the ranking was Inoserp Europe, Viperfav, ViperaTAb. Our data reveal ontogenetic variation in V. a meridionalis, but this difference may not be of clinical concern as antivenom was effective at neutralizing both adult and neonate venom phenotypes. Regardless, our results highlight
a previously undocumented ontogenetic shift, likely driven by the documented difference in prey preference observed for this species across age classes.
America. Mitochondrial DNA analysis demonstrates a significant genetic divergence between the species,bwhich is supported by a notable difference in sexual size dimorphism (SSD) intensity between the two species, along with other morphological differences. This paper also rectifies earlier oversights in the description of the new species and clarifies taxonomic ambiguities in compliance with the International Code of Zoological Nomenclature (henceforth ICZN). In addition, we designate a neotype for E. murinus to stabilize the group. In an effort to honor Indigenous nations, E. akayima sp. nov. derives its name from the Carib language, advocating for the inclusion of traditional names in scientific discourse. Our paper not
only contributes to the taxonomic stability of anacondas but also advocates for the usage of Indigenous names in zoological nomenclature by adopting amore inclusive and flexible approach to the ICZN and eliminating unintended exclusionary practices that we have inherited in science as in other disciplines.
The snake genera Atropoides, Cerrophidion, and Metlapilcoaltus form a clade of Neotropical pit vipers distributed across Mexico and Central America. This study evaluated the myotoxic and neurotoxic effects of nine species of Atropoides, Cerrophidion and Metlapilcoatlus, and the neutralising efficacy of the ICP antivenom from Costa Rica against these effects, in the chick biventer cervicis nerve-muscle preparation. Given the prominence of PLA2s within the venom proteomes of these species, we also aimed to determine the neutralising potency of the PLA2 inhibitor, varespladib.
Results:
All venoms showed myotoxic, and potential neurotoxic effects, with differential intra-genera and inter-genera potency. This variation was also seen in the antivenoms ability to neutralise the muscle damaging pathophysiological effects observed. Variation was also seen in the relative response to the PLA2-inhibitor varespladib. While the myotoxic effects of M. mexicanus and M. nummifer venoms were effectively neutralised by varespladib, indicating myotoxicity is PLA2 mediated, those of C. godmani and M. olmec venoms were not, revealing that the myotoxicity is driven by non-PLA2 toxin types.
Conclusions:
This study characterises the myotoxic and neurotoxic venom activity, as well as neutralisation of venom effects from the Atropoides, Cerrophidion, and Metlapilcoatlus clade of American Crotalids. Our findings contribute significant clinical and evolutionary knowledge to a clade of poorly researched snakes. In addition, these results provide a platform for future research into the reciprocal interaction between ecological niche specialisation and venom evolution, as well as highlighting the need to test purified toxins to accurately evaluate the potential effects observed in these venoms.
V. a. meridionalis venoms produced procoagulant effects, the effects produced by neonate venom were more potent. Consistent with this, neonate venom was a stronger activator of blood-clotting zymogens, converting them into their active forms, with a rank order of Factor X >> Factor VII> Factor XII. Conversely, the less potent adult venom had a rank order of FXII marginally more activated than Factor VII, and both much more so than Factor X. This adds to the growing body of evidence that activation of factors besides FII (prothrombin) and FX are significant variables in reptile venom-induced coagulopathy. Although all three examined antivenoms displayed effective
neutralization of both neonate and adult V. a. meridionalis venoms, they generally showed higher efficacy on adult venom than on neonate venom. The ranking of antivenom efficacy against neonate venom, from the most effective to the least effective, were Viperfav, Inoserp Europe, ViperaTAb; for
adult venom, the ranking was Inoserp Europe, Viperfav, ViperaTAb. Our data reveal ontogenetic variation in V. a meridionalis, but this difference may not be of clinical concern as antivenom was effective at neutralizing both adult and neonate venom phenotypes. Regardless, our results highlight
a previously undocumented ontogenetic shift, likely driven by the documented difference in prey preference observed for this species across age classes.
America. Mitochondrial DNA analysis demonstrates a significant genetic divergence between the species,bwhich is supported by a notable difference in sexual size dimorphism (SSD) intensity between the two species, along with other morphological differences. This paper also rectifies earlier oversights in the description of the new species and clarifies taxonomic ambiguities in compliance with the International Code of Zoological Nomenclature (henceforth ICZN). In addition, we designate a neotype for E. murinus to stabilize the group. In an effort to honor Indigenous nations, E. akayima sp. nov. derives its name from the Carib language, advocating for the inclusion of traditional names in scientific discourse. Our paper not
only contributes to the taxonomic stability of anacondas but also advocates for the usage of Indigenous names in zoological nomenclature by adopting amore inclusive and flexible approach to the ICZN and eliminating unintended exclusionary practices that we have inherited in science as in other disciplines.
simple anatomy, they are capable of subduing or repelling prey and predator species that are
far more complex and recently evolved. Utilizing specialized penetrating nematocysts,
cnidarians inject the nematocyst content or “venom” that initiates toxic and immunological
reactions in the envenomated organism. These venoms contain enzymes, potent pore
forming toxins, and neurotoxins. Enzymes include lipolytic and proteolytic proteins that
catabolize prey tissues. Cnidarian pore forming toxins self-assemble to form robust
membrane pores that can cause cell death via osmotic lysis. Neurotoxins exhibit rapid ion
channel specific activities. In addition, certain cnidarian venoms contain or induce the
release of host vasodilatory biogenic amines such as serotonin, histamine, bunodosine and
caissarone accelerating the pathogenic effects of other venom enzymes and porins. The
cnidarian attacking/defending mechanism is fast and efficient, and massive envenomation
of humans may result in death, in some cases within a few minutes to an hour after sting.
The complexity of venom components represents a unique therapeutic challenge and probably
reflects the ancient evolutionary history of the cnidarian venom system. Thus, they are
invaluable as a therapeutic target for sting treatment or as lead compounds for drug design.
technical difficulties in recovery of the complex venom from the microscopic nematocysts.
Here we report a newly developed rapid, repeatable and cost effective technique of venom
preparation, using ethanol to induce nematocyst discharge and to recover venom contents
in one step. Our model species was the Australian box jellyfish (Chironex fleckeri), which
has a notable impact on public health. By utilizing scanning electron microscopy and
light microscopy, we examined nematocyst external morphology before and after ethanol
treatment and verified nematocyst discharge. Further, to investigate nematocyst content or
“venom” recovery, we utilized both top-down and bottom-up transcriptomics–proteomics
approaches and compared the proteome profile of this new ethanol recovery based method
to a previously reported high activity and recovery protocol, based upon density purified
intact cnidae and pressure induced disruption. In addition to recovering previously
characterized box jellyfish toxins, including CfTX-A/B and CfTX-1, we recovered putative
metalloproteases and novel expression of a small serine protease inhibitor. This study not
only reveals a much more complex toxin profile of Australian box jellyfish venom but also
suggests that ethanol extraction method could augment future cnidarian venom proteomics
research efforts.