New insights into the phylogeographic distribution of the 3FTx/PLA2 venom dichotomy across genus Micrurus in South America

Sanz, Libia; Quesada-Bernat, Sarai; Ramos, Tyelli dos Santos; Casais-e-Silva, Luciana Lyra; Corrêa-Netto, Carlos; Silva-Haad, Juan José; Sasa, Mahmood; Lomonte, Bruno; Calvete, Juan J.

doi:10.1016/j.jprot.2019.03.014

Cited by 39 publications

(42 citation statements)

References 75 publications

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“…In brief, the Sri Lankan N. naja, representing the southernmost dispersed population exhibited a venom phenotype characterized by a lower alpha-neurotoxin abundance in exchange for a relatively higher CTX abundance, as opposed to that observed in the northern lineages from Pakistan, Indian Punjab and West Bengal [6,8,44]. Similar patterns of toxin compositional dichotomy within closely related species have been found among evolutionarily distant snake lineages from Elapidae (kraits, sea snakes, coral snakes) [95][96][97][98][99][100], and Viperidae (rattlesnakes, Russell's vipers, etc.) [18,91,101,102], suggesting that intra-species venom phenotypic dichotomy might be more common than previously thought, and underscoring its impact on the effectiveness of antivenom treatment.…”

Section: Comparison Of Naja Naja Venomics and Implication On Antivenom Treatment For Cobra Bite Envenomationmentioning

confidence: 67%

Elucidating the Venom Diversity in Sri Lankan Spectacled Cobra (Naja naja) through De Novo Venom Gland Transcriptomics, Venom Proteomics and Toxicity Neutralization

Wong

Tan

et al. 2021

Toxins

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Inadequate effectiveness of Indian antivenoms in treating envenomation caused by the Spectacled Cobra/Indian Cobra (Naja naja) in Sri Lanka has been attributed to geographical variations in the venom composition. This study investigated the de novo venom-gland transcriptomics and venom proteomics of the Sri Lankan N. naja (NN-SL) to elucidate its toxin gene diversity and venom variability. The neutralization efficacy of a commonly used Indian antivenom product in Sri Lanka was examined against the lethality induced by NN-SL venom in mice. The transcriptomic study revealed high expression of 22 toxin genes families in NN-SL, constituting 46.55% of total transcript abundance. Three-finger toxins (3FTX) were the most diversely and abundantly expressed (87.54% of toxin gene expression), consistent with the dominance of 3FTX in the venom proteome (72.19% of total venom proteins). The 3FTX were predominantly S-type cytotoxins/cardiotoxins (CTX) and α-neurotoxins of long-chain or short-chain subtypes (α-NTX). CTX and α-NTX are implicated in local tissue necrosis and fatal neuromuscular paralysis, respectively, in envenomation caused by NN-SL. Intra-species variations in the toxin gene sequences and expression levels were apparent between NN-SL and other geographical specimens of N. naja, suggesting potential antigenic diversity that impacts antivenom effectiveness. This was demonstrated by limited potency (0.74 mg venom/ml antivenom) of the Indian polyvalent antivenom (VPAV) in neutralizing the NN-SL venom. A pan-regional antivenom with improved efficacy to treat N. naja envenomation is needed.

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Section: Comparison Of Naja Naja Venomics and Implication On Antivenom Treatment For Cobra Bite Envenomationmentioning

confidence: 67%

Elucidating the Venom Diversity in Sri Lankan Spectacled Cobra (Naja naja) through De Novo Venom Gland Transcriptomics, Venom Proteomics and Toxicity Neutralization

Wong

Tan

et al. 2021

Toxins

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“…Contrasting our lack of knowledge on the mechanisms that underlie the population and developmental variational properties and dynamics of snake venoms, we have a much better knowledge about the processes that shape snake venoms on macroevolutionary scales (between species). For example, we can infer nodes where particularly influential shifts were made in genotype-phenotype space by mapping the venom phenotype profiles of a species clade across its phylogeny ( Pla et al, 2013 , 2017a ; Gibbs et al, 2013 ; Lomonte et al, 2014 ; Calvete et al, 2017 ; Ainsworth et al, 2018 ; Calvete, 2019 ; Sanz et al, 2019a ; Zaher et al, 2019 ; Kazandjian et al, 2021 ). Further, ancestral structure inference may allow the reconstruction of the evolutionary origin of key mutations across the history of individual toxins ( Whittington et al, 2018 ) and functional snake venom clades ( Blanchet et al, 2017 ; Ainsworth et al, 2018 ; Jackson and Koludarov, 2020 ; Holding et al, 2021 ).…”

Section: Snakebite and The “Ecological Stance”mentioning

confidence: 99%

“…Identifying the specific pressures that tailored the composition of extant medically relevant venoms, e.g. by inferring influential nodes across phylogeny ( Calvete, 2013 , 2019 ; Pla et al, 2013 , 2017a ; Gibbs et al, 2013 ; Lomonte et al, 2014 ; Blanchet et al, 2017 ; Calvete et al, 2017 ; Ainsworth et al, 2018 ; Sanz et al, 2019a ; Zaher et al, 2019 ; Jackson and Koludarov, 2020 ; Kazandjian et al, 2021 ; Holding et al, 2021 ), may have implications for the clinical treatment of human envenomings. The thesis advocated in this essay is that integration and contextualisation of complementary evolutionary, ecological, and clinical toxinological information represents a powerful holistic approach to tackle the global challenge of snake envenoming.…”

Section: Evolutionary Ecology and Clinical Impact Of Snake Venoms—a Brief Introductionmentioning

confidence: 99%

Mutual enlightenment: A toolbox of concepts and methods for integrating evolutionary and clinical toxinology via snake venomics and the contextual stance

et al. 2021

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Snakebite envenoming is a neglected tropical disease that may claim over 100,000 human lives annually worldwide. Snakebite occurs as the result of an interaction between a human and a snake that elicits either a defensive response from the snake or, more rarely, a feeding response as the result of mistaken identity. Snakebite envenoming is therefore a biological and, more specifically, an ecological problem. Snake venom itself is often described as a “cocktail”, as it is a heterogenous mixture of molecules including the toxins (which are typically proteinaceous) responsible for the pathophysiological consequences of envenoming. The primary function of venom in snake ecology is pre-subjugation, with defensive deployment of the secretion typically considered a secondary function. The particular composition of any given venom cocktail is shaped by evolutionary forces that include phylogenetic constraints associated with the snake's lineage and adaptive responses to the snake's ecological context, including the taxa it preys upon and by which it is predated upon. In the present article, we describe how conceptual frameworks from ecology and evolutionary biology can enter into a mutually enlightening relationship with clinical toxinology by enabling the consideration of snakebite envenoming from an “ecological stance”. We detail the insights that may emerge from such a perspective and highlight the ways in which the high-fidelity descriptive knowledge emerging from applications of -omics era technologies – “venomics” and “antivenomics” – can combine with evolutionary explanations to deliver a detailed understanding of this multifactorial health crisis.

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“…In Brazil, the Micrurus genera of coral snakes represents almost the totality of elapids, counting about 34 species [ 1 ] widespread throughout the country. Just as other coral snakes, the venoms of Brazilian Micrurus are predominant in three-finger toxins (3FTxs) and phospholipase A 2 (PLA 2 ), along with other less abundant proteins [ 2 , 3 , 4 ]. They may cause several injuries on envenomed animals such as myotoxicity, edema, nephrotoxicity, hemorrhages, and neurotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Three-Finger Toxins from Brazilian Coral Snakes: From Molecular Framework to Insights in Biological Function

Kleiz-Ferreira

Cirauqui

Trajano

et al. 2021

Toxins

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Studies on 3FTxs around the world are showing the amazing diversity in these proteins both in structure and function. In Brazil, we have not realized the broad variety of their amino acid sequences and probable diversified structures and targets. In this context, this work aims to conduct an in silico systematic study on available 3FTxs found in Micrurus species from Brazil. We elaborated a specific guideline for this toxin family. First, we grouped them according to their structural homologue predicted by HHPred server and further curated manually. For each group, we selected one sequence and constructed a representative structural model. By looking at conserved features and comparing with the information available in the literature for this toxin family, we managed to point to potential biological functions. In parallel, the phylogenetic relationship was estimated for our database by maximum likelihood analyses and a phylogenetic tree was constructed including the homologous 3FTx previously characterized. Our results highlighted an astonishing diversity inside this family of toxins, showing some groups with expected functional similarities to known 3FTxs, and pointing out others with potential novel roles and perhaps structures. Moreover, this classification guideline may be useful to aid future studies on these abundant toxins.

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New insights into the phylogeographic distribution of the 3FTx/PLA2 venom dichotomy across genus Micrurus in South America

Cited by 39 publications

References 75 publications

Elucidating the Venom Diversity in Sri Lankan Spectacled Cobra (Naja naja) through De Novo Venom Gland Transcriptomics, Venom Proteomics and Toxicity Neutralization

Elucidating the Venom Diversity in Sri Lankan Spectacled Cobra (Naja naja) through De Novo Venom Gland Transcriptomics, Venom Proteomics and Toxicity Neutralization

Mutual enlightenment: A toolbox of concepts and methods for integrating evolutionary and clinical toxinology via snake venomics and the contextual stance

Three-Finger Toxins from Brazilian Coral Snakes: From Molecular Framework to Insights in Biological Function

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