Proteomic and toxicological profiling of the venom of Bothrocophias campbelli, a pitviper species from Ecuador and Colombia

Salazar-Valenzuela, David; Mora-Obando, Diana; Fernández, María Laura; Loaiza-Lange, Amaru; Gibbs, H. Lisle; Lomonte, Bruno

doi:10.1016/j.toxicon.2014.07.012

Cited by 24 publications

(19 citation statements)

References 28 publications

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“…Many studies have indeed clearly documented that both cofactors significantly affect relative coagulotoxicity (50-53, 56-59, 66-76). However, despite this critical importance having been known for decades, assay designs in many snake venom coagulotoxicity studies have included Ca 2+ but not phospholipids (77-93) or neither of the clotting cofactors (32, [94][95][96][97][98][99][100][101][102][103][104]. This may dramatically skew the results, to the point that procoagulant activity might be missed entirely for venoms that are inactive in the absence of clotting cofactors or generate enzymes such as FXa which are themselves obligately dependent upon Ca 2+ for activity.…”

Section: Introductionmentioning

confidence: 99%

A Clot Twist: Extreme Variation in Coagulotoxicity Mechanisms in Mexican Neotropical Rattlesnake Venoms

et al. 2021

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Rattlesnakes are a diverse clade of pit vipers (snake family Viperidae, subfamily Crotalinae) that consists of numerous medically significant species. We used validated in vitro assays measuring venom-induced clotting time and strength of any clots formed in human plasma and fibrinogen to assess the coagulotoxic activity of the four medically relevant Mexican rattlesnake species Crotalus culminatus, C. mictlantecuhtli, C. molossus, and C. tzabcan. We report the first evidence of true procoagulant activity by Neotropical rattlesnake venom in Crotalus culminatus. This species presented a strong ontogenetic coagulotoxicity dichotomy: neonates were strongly procoagulant via Factor X activation, whereas adults were pseudo-procoagulant in that they converted fibrinogen into weak, unstable fibrin clots that rapidly broke down, thereby likely contributing to net anticoagulation through fibrinogen depletion. The other species did not activate clotting factors or display an ontogenetic dichotomy, but depleted fibrinogen levels by cleaving fibrinogen either in a destructive (non-clotting) manner or via a pseudo-procoagulant mechanism. We also assessed the neutralization of these venoms by available antivenom and enzyme-inhibitors to provide knowledge for the design of evidence-based treatment strategies for envenomated patients. One of the most frequently used Mexican antivenoms (Bioclon Antivipmyn®) failed to neutralize the potent procoagulant toxic action of neonate C. culminatus venom, highlighting limitations in snakebite treatment for this species. However, the metalloprotease inhibitor Prinomastat substantially thwarted the procoagulant venom activity, while 2,3-dimercapto-1-propanesulfonic acid (DMPS) was much less effective. These results confirm that venom-induced Factor X activation (a procoagulant action) is driven by metalloproteases, while also suggesting Prinomastat as a more promising potential adjunct treatment than DMPS for this species (with the caveat that in vivo studies are necessary to confirm this potential clinical use). Conversely, the serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) inhibited the direct fibrinogen cleaving actions of C. mictlantecuhtli venom, thereby revealing that the pseudo-procoagulant action is driven by kallikrein-type serine proteases. Thus, this differential ontogenetic variation in coagulotoxicity patterns poses intriguing questions. Our results underscore the need for further research into Mexican rattlesnake venom activity, and also highlights potential limitations of current antivenom treatments.

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Section: Introductionmentioning

confidence: 99%

A Clot Twist: Extreme Variation in Coagulotoxicity Mechanisms in Mexican Neotropical Rattlesnake Venoms

et al. 2021

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“…Emergency lateral and medial fasciotomies were performed to decompress the three compartments in the extremity. A patient with severe poisoning should ideally receive 12 vials of antiophidic serum dissolved in 250 ml of saline [2][3][4][5][6]. However, our patient received only eight vials at the first point of care, which presumably failed to sufficiently neutralize the venom, leading to further tissue destruction and the development of compartment syndrome.…”

Section: Discussionmentioning

confidence: 99%

A Rare and Urgent Consequence After a Snake Bite

Lizarzaburu-Ortiz¹,

Yumi²,

Carvajal³

et al. 2022

Cureus

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Snake bites (ophidism) constitute a public health problem in tropical and subtropical countries, due to their lethality, and the lack of access to prompt treatment in these regions. Catastrophic consequences follow the injection of the venom due to its proteolytic, procoagulant, hemorrhagic, nephrotoxic, vasculotoxic, and myonecrotizing properties, which can lead to severe complications if not managed promptly and adequately. In this report, we present the case of a 26-year-old male patient who suffered a snake bite (Bothrops asper) on the back of his right foot. Initially, he received eight vials of antivenom and was transferred to a specialized center. However, a few hours after his arrival, a necrotic wound developed on the back of the foot along with compartment syndrome, and hence emergency fasciotomies had to be performed and the patient was admitted to the ICU for multidisciplinary management and continuous monitoring. After 14 days, fasciotomy closure and eschar incision on the dorsum of the foot were performed along with an aesthetic reconstruction with an advancement flap and full-thickness graft. The patient had a satisfactory outcome thanks to the prompt evaluation and access to a unit with experience in managing highly complex cases. Our case highlights the importance of prompt and meticulous assessment after a snake bite due to its potential for causing highly complex clinical scenarios, and early diagnosis, proper management, and continuous multidisciplinary monitoring are key for a favorable prognosis. In many cases, these bites can lead to significant tissue loss and may necessitate the amputation of the affected limb. In severe cases, compartment syndrome frequently ensues and further complicates the management and increases morbidity if not recognized and managed promptly.

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“…Snake toxin genes are coded by gene families and produce gene isoforms through the process of duplications ( Casewell et al, 2013 ; Fry, 2005 ). Several studies on the venom-associated proteins from New World vipers have classified the venoms into four groups (type I–IV), based on the relative abundance of toxin families ( Calvete, 2013 ; Gibbs et al, 2013 ; Goncalves-Machado et al, 2016 ; Jimenez-Charris et al, 2015 ; Lomonte et al, 2014 ; Mora-Obando et al, 2014 ; Pla et al, 2017 ; Salazar-Valenzuela et al, 2014 ). The different groups are: snake venom metalloproteinase-predominant (type I), heterodimeric β -neurotoxic PLA2 –rich (type II), serine proteinases and PLA2 (type III) and type IV, which is similar to type III but with significant higher concentration of snake venom metalloproteinases ( Calvete, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Comparative analyses of putative toxin gene homologs from an Old World viper,Daboia russelii

Krishnan

Panda

2017

PeerJ

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Availability of snake genome sequences has opened up exciting areas of research on comparative genomics and gene diversity. One of the challenges in studying snake genomes is the acquisition of biological material from live animals, especially from the venomous ones, making the process cumbersome and time-consuming. Here, we report comparative sequence analyses of putative toxin gene homologs from Russell’s viper (Daboia russelii) using whole-genome sequencing data obtained from shed skin. When compared with the major venom proteins in Russell’s viper studied previously, we found 45–100% sequence similarity between the venom proteins and their putative homologs in the skin. Additionally, comparative analyses of 20 putative toxin gene family homologs provided evidence of unique sequence motifs in nerve growth factor (NGF), platelet derived growth factor (PDGF), Kunitz/Bovine pancreatic trypsin inhibitor (Kunitz BPTI), cysteine-rich secretory proteins, antigen 5, andpathogenesis-related1 proteins (CAP) and cysteine-rich secretory protein (CRISP). In those derived proteins, we identified V11 and T35 in the NGF domain; F23 and A29 in the PDGF domain; N69, K2 and A5 in the CAP domain; and Q17 in the CRISP domain to be responsible for differences in the largest pockets across the protein domain structures in crotalines, viperines and elapids from the in silico structure-based analysis. Similarly, residues F10, Y11 and E20 appear to play an important role in the protein structures across the kunitz protein domain of viperids and elapids. Our study highlights the usefulness of shed skin in obtaining good quality high-molecular weight DNA for comparative genomic studies, and provides evidence towards the unique features and evolution of putative venom gene homologs in vipers.

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Proteomic and toxicological profiling of the venom of Bothrocophias campbelli, a pitviper species from Ecuador and Colombia

Cited by 24 publications

References 28 publications

A Clot Twist: Extreme Variation in Coagulotoxicity Mechanisms in Mexican Neotropical Rattlesnake Venoms

A Clot Twist: Extreme Variation in Coagulotoxicity Mechanisms in Mexican Neotropical Rattlesnake Venoms

A Rare and Urgent Consequence After a Snake Bite

Comparative analyses of putative toxin gene homologs from an Old World viper,Daboia russelii

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