Rattling the border wall: Pathophysiological implications of functional and proteomic venom variation between Mexican and US subspecies of the desert rattlesnake Crotalus scutulatus

Abstract

While some US populations of the Mohave rattlesnake (Crotalus scutulatus scutulatus) are infamous for being potently neurotoxic, the Mexican subspecies C. s. salvini (Huamantlan rattlesnake) has been largely unstudied beyond crude lethality testing upon mice. In this study we show that at least some populations of this snake are as potently neurotoxic as its northern cousin. Testing of the Mexican antivenom Antivipmyn showed a complete lack of neutralisation for the neurotoxic effects of C. s. salvini venom, while the neurotoxic effects of the US subspecies C. s. scutulatus were time-delayed but ultimately not eliminated. These results document unrecognised potent neurological effects of a Mexican snake and highlight the medical importance of this subspecies, a finding augmented by the ineffectiveness of the Antivipmyn antivenom. These results also influence our understanding of the venom evolution of Crotalus scutulatus, suggesting that neurotoxicity is the ancestral feature of this species, with the US populations which lack neurotoxicity being derived states.

Factor X activating Atractaspis snake venoms and the relative coagulotoxicity neutralising efficacy of African antivenoms

“…Fluorescent substrate cleavage studies were conducted as previously described by us (Cipriani et al, 2017;Debono et al, 2017;Dobson et al, 2017;Koludarov et al, 2017). A working stock solution of freeze-dried venom was reconstituted in a buffer containing 50% deionised H2O/50% glycerol (>99.9%, Sigma) at a 1:1 ratio to preserve enzymatic activity and reduce enzyme degradation with the final venom concentration of 0.1 mg/ml, and then stored at -20°C.…”

A blood bond: evolutionary, pathophysiological and biodiscovery implications of coagulotoxic snake venoms

“…Ecological niche partitioning and a shift in diet would contribute to venom evolution of the species across varying localities and habitats, with consequential impacts upon relative clinical effects Fry et al, 2008). Such wide variation depicted within a single genus has also been shown within many other groups of closely related snakes, each inhabiting slightly varied ecological niches (Debono et al, 2019a;Debono et al, 2019c;Debono et al, 2017a;Dobson et al, 2018;Rogalski et al, 2017) as well as variation between localities of the same species (Sousa et al, 2018). While some ontogenetic shift has been shown within one species of Gloydius (Gao et al, 2013), due to lack of sample availability the impact upon relative coagulotoxicity was not investigated in the present study and should be the subject of future work.…”

“…Venoms from Azemiops feae, Calloselasma rhodostoma, Deinagkistrodon acutus, Hypnale hypnale, Tropidolaemus subannulatus and Tropidolaemus wagleri were investigated for ability to cleave fibrinogen using protocols previously described by us (Debono et al, 2019c;Dobson et al, 2018).…”

“…Haemorrhagic effects are potentiated by fibrinogenolytic enzymes which may act upon fibrinogen to either directly produce anticoagulation, by destructively cleaving fibrinogen, or to indirectly produce anticoagulation by cleaving fibrinogen to form short-lived, weak clots in a pseudo-procoagulant manner Debono et al, 2019c;Dobson et al, 2018;Esnouf and Tunnah, 1967;Huang et al, 1992;Levy and Del Zoppo, 2006;Nielsen, 2016a;Premawardena et al, 1998;Trookman et al, 2009;Zulys et al, 1989).…”

“…It has been established in the literature that venom composition between closely related species, or within different populations of a single species, may vary considerably due to differential pressures regarding prey availability and prey escape potential. This variation has direct implications for the relative clinical usefulness of antivenoms against species not included in the immunising mixture, or varying populations of the species used (Debono et al, 2017a;Dobson et al, 2018;Fry et al, 2003a;Lister et al, 2017;Rogalski et al, 2017;Sousa et al, 2018;Sunagar et al, 2014;Tan et al, 2017a;Yang et al, 2016;Zdenek et al, 2019). Many current antivenomic strategies are mostly limited to the immunoreactivity of the antivenom towards the venom components, these do not ascertain whether the antivenom is effective in neutralising venom pathological functions (Jones et al, 2019;Williams et al, 2011;Xu et al, 2017).…”