Abstract
The use of venom in predation exerts a corresponding selection pressure for the evolution of venom resistance. One of the mechanisms related to venom resistance in animals (predators or prey of snakes) is the presence of molecules in the blood that can bind venom toxins, and inhibit their pharmacological effects. One such toxin type are venom phospholipase A2s (PLA2s), which have diverse effects including anticoagulant, myotoxic, and neurotoxic activities. BoaγPLI isolated from the blood of Boa constrictor has been previously shown to inhibit venom PLA2s that induced myotoxic and edematogenic activities. Recently, in addition to its previously described and very potent neurotoxic effect, the venoms of American coral snakes (Micrurus species) have been shown to have anticoagulant activity via PLA2 toxins. As coral snakes eat other snakes as a major part of their diet, neonate Boas could be susceptible to predation by this sympatric species. Thus, this work aimed to ascertain if BoaγPLI provided a protective effect against the anticoagulant toxicity of venom from the model species Micrurus laticollaris in addition to its ability shown previously against other toxin types. Using a STA R Max coagulation analyser robot to measure the effect upon clotting time, and TEG5000 thromboelastographers to measure the effect upon clot strength, we evaluated the ability of BoaγPLI to inhibit M. laticollaris venom. Our results indicate that BoaγPLI is efficient at inhibiting the M. laticollaris anticoagulant effect, reducing the time of coagulation (restoring them closer to non-venom control values) and increasing the clot strength (restoring them closer to non-venom control values). These findings demonstrate that endogenous PLA2 inhibitors in the blood of non-venomous snakes are multi-functional and provide broad resistance against a myriad of venom PLA2-driven toxic effects including coagulotoxicity, myotoxicity, and neurotoxicity. This novel form of resistance could be evidence of selective pressures caused by predation from venomous snakes and stresses the need for field-based research aimed to expand our understanding of the evolutionary dynamics of such chemical arms race.
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Funding
This research was funded by Australian Research Council Discovery Project DP190100304; Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP 2018/25786–0); and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001.
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Conceptualization, B.G.F. and A.M.T.A.; methodology, B.G.F., C.N.Z.; validation, C.F.B.R., C.N.Z.; formal analysis, C.F.B.R., C.N.Z; investigation, C.F.B.R., C.N.Z., C.S.S, K.M.Z., K.F.G., M.B.V., E.N., A.A., B.G.F., A.M.T.A.; resources, B.G.F., A.M.T.A., K.F.G.; data curation, C.F.B.R., C.Z.N.; writing—original draft preparation, C.F.B.R., A.M.T.A., B.F.G.; writing—review and editing, C.F.B.R. C.N.Z., C.S.S., K.M.Z., A.M.T.A., B.G.F.; supervision, C.N.Z., A.M.T.A, B.G.F.; project administration, A.M.T.A., B.G.F.; funding acquisition, C.F.B.R, A.M.T.A., B.G.F. All authors have read and agreed to the published version of the manuscript.
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Plasma work was done under the Australian Red Cross Research Agreement #18-03QLD-09; University of Queensland Human Ethics Committee Approval #2016000256. The BoaγPLI was purified under the Instituto Butantan Ethics Committee Approval # 6916110917.
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Rodrigues, C.F.B., Zdenek, C.N., Serino-Silva, C. et al. BoaγPLI from Boa constrictor Blood is a Broad-Spectrum Inhibitor of Venom PLA2 Pathophysiological Actions. J Chem Ecol 47, 907–914 (2021). https://doi.org/10.1007/s10886-021-01289-4
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DOI: https://doi.org/10.1007/s10886-021-01289-4