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Juan J. Calvete - One of the best experts on this subject based on the ideXlab platform.
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venomics of the duvernoy s gland secretion of the false coral snake rhinobothryum bovallii andersson 1916 and assessment of venom lethality towards synapsid and diapsid animal models
Journal of Proteomics, 2020Co-Authors: Juan J. Calvete, Bruno Lomonte, Libia Sanz, Fabian Bonilla, Sofia Granadosmartinez, Mahmood SasaAbstract:Abstract The Duvernoy's gland Secretory proteome of the false coral snake Rhinobothryum bovallii (Costa Rica), unveiled applying bottom-up venomics, comprises a handful of toxins belonging to only three Protein families, three-finger toxin (3FTx), Cysteine-Rich Secretory Protein (CRISP), and snake venom metalloprotease (PIII-SVMP). Except for small differences in the relative abundance of the PIII-SVMPs, which may be due to individual variability, no evidence of geographic variability or ontogenetic changes was found among the venom proteomes of the juvenile and adult R. bovallii snakes sampled. Major monomeric (86.5%mol) and minor dimeric (2.8%mol) 3FTxs dominate the toxin arsenal of the Costa Rican false coral snake. The remaining 10.7% of the venom proteome comprises CRISP (8.2%) and PIII-SVMP (2.4%) molecules. In vivo lethality assays showed that R. bovallii produces venom that is non-toxic towards mammalian prey, and which exerts a different toxic effect on domestic chicken chicks and baby green iguana. Toxicovenomic analysis of R. bovallii venom in the iguana model identified two 3FTx RP-HPLC fractions that faithfully mimicked the irreversible immobilizing effect of the whole venom. Biological significance With more than 2200 species in family Colubridae (sensu lato), rear-fanged snakes comprise approximately two-thirds of the extant species of advanced snakes. Snakebites from venomous snakes that are of medical concern are predominantly from front-fanged snakes of families Viperidae and Elapidae. On the other hand, rear-fanged snakes have been conventionally considered non-venomous, and thus their venoms have remained a largely untapped area of venomics. However, increasing documentation of life-threadening, even fatal, envenomings from rear-fanged snakes has sparked interest in their venoms. Appying bottom-up venomics we have revealed that the Duvernoy's gland Secretory proteome of R. bovallii comprises a handful of toxins belonging to only three Protein families, with slow-acting three-finger toxins (3FTx) that are non-toxic towards mammalian prey and show preference towards diapsid taxa representing the dominant structural and functional Proteins. Our work documents for the first time 3FTxs exerting different effect in an avian model than in a reptile model. Besides, the 3FTx fractions that faithfully mimicked the irreversible iguana-immobilizing effect of the whole venom were identified through toxicovenomic analysis of R. bovallii venom on Iguana iguana. Our work underscores the importance of using biologically-relevant animal toxicity models for investigating the biological roles of venoms in an evolutionary-ecological context.
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Vipera berus berus Venom from Russia: Venomics, Bioactivities and Preclinical Assessment of Microgen Antivenom
MDPI AG, 2019Co-Authors: Ruslan I. Al-shekhadat, Alvaro Segura, Juan J. Calvete, Ksenia S. Lopushanskaya, José María Gutiérrez, Davinia PlaAbstract:The common European adder, Vipera berus berus, is a medically relevant species, which is widely distributed in Russia and thus, is responsible for most snakebite accidents in Russia. We have investigated the toxic and enzymatic activities and have determined the proteomic composition of its venom. Phospholipases A2 (PLA2, 25.3% of the venom proteome), serine Proteinases (SVSP, 16.2%), metalloProteinases (SVMP, 17.2%), vasoactive peptides (bradykinin-potentiating peptides (BPPs), 9.5% and C-type natriuretic peptides (C-NAP, 7.8%), Cysteine-Rich Secretory Protein (CRISP, 8%) and L-amino acid oxidase (LAO, 7.3%) represent the major toxin classes found in V. b. berus (Russia) venom. This study was also designed to assess the in vivo and in vitro preclinical efficacy of the Russian Microgen antivenom in neutralizing the main effects of V. b. berus venom. The results show that this antivenom is capable of neutralizing the lethal, hemorrhagic and PLA2 activities. Third-generation antivenomics was applied to quantify the toxin-recognition landscape and the maximal binding capacity of the antivenom for each component of the venom. The antivenomics analysis revealed that 6.24% of the anti-V. b. berus F(ab’)2 molecules fraction are toxin-binding antibodies, 60% of which represent clinically relevant antivenom molecules
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Immunoaffinity chromatography-based antivenomic analysis of the immunoreactivity of polyspecific and monospecific antivenoms towards the venom of L. muta muta from Colombia.
2017Co-Authors: Marvin Madrigal, Libia Sanz, José María Gutiérrez, Davinia Pla, Elexandra Barboza, Cynthia Arroyo-portilla, Carlos Corrêa-netto, Alberto Alape-girón, Marietta Flores-díaz, Juan J. CalveteAbstract:Panels display reverse-phase separations of whole venom components, and non-retained (A, C, E, G, and I) and the retained (B, D, F, H, and J) fractions recovered, respectively, from the affinity columns of immobilized BCL, BL, AL, AB, and AC antivenoms. Panels K and L, non-retained and retained venom fractions by immobilized equine control immunoglobulins. CRISP, Cysteine-Rich Secretory Protein. Other Protein acronyms as in the legend of Fig 2.
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Immunoaffinity chromatography-based antivenomic analysis of the immunoreactivity of polyspecific and monospecific antivenoms towards the venom of L. muta muta from Cascalheira (Brazil).
2017Co-Authors: Marvin Madrigal, Libia Sanz, José María Gutiérrez, Davinia Pla, Elexandra Barboza, Cynthia Arroyo-portilla, Carlos Corrêa-netto, Alberto Alape-girón, Marietta Flores-díaz, Juan J. CalveteAbstract:Panels display reverse-phase separations of whole venom components, and non-retained (A, C, E, G, and I) and the retained (B, D, F, H, and J) fractions recovered, respectively, from the affinity columns of immobilized BCL, BL, L, B, and C antivenoms. Panels K and L, non-retained and retained venom fractions by immobilized equine control immunoglobulins. CRISP, Cysteine-Rich Secretory Protein; other acronyms as in the legend of Fig 2.
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comparative venomics of the prairie rattlesnake crotalus viridis viridis from colorado identification of a novel pattern of ontogenetic changes in venom composition and assessment of the immunoreactivity of the commercial antivenom crofab
Journal of Proteomics, 2015Co-Authors: Juan J. Calvete, Libia Sanz, Anthony J Saviola, Todd A Castoe, Stephen P MackessyAbstract:Abstract Here we describe and compare the venomic and antivenomic characteristics of both neonate and adult Prairie Rattlesnake (Crotalus viridis viridis) venoms. Although both neonate and adult venoms contain unique components, similarities among Protein family content were seen. Both neonate and adult venoms consisted of myotoxin, bradykinin-potentiating peptide (BPP), phospholipase A2 (PLA2), Zn2 +-dependent metalloProteinase (SVMP), serine Proteinase, L-amino acid oxidase (LAAO), Cysteine-Rich Secretory Protein (CRISP) and disintegrin families. Quantitative differences, however, were observed, with venoms of adults containing significantly higher concentrations of the non-enzymatic toxic compounds and venoms of neonates containing higher concentrations of pre-digestive enzymatic Proteins such as SVMPs. To assess the relevance of this venom variation in the context of snakebite and snakebite treatment, we tested the efficacy of the common antivenom CroFab® for recognition of both adult and neonate venoms in vitro. This comparison revealed that many of the major Protein families (SVMPs, CRISP, PLA2, serine proteases, and LAAO) in both neonate and adult venoms were immunodepleted by the antivenom, whereas myotoxins, one of the major toxic components of C. v. viridis venom, in addition to many of the small peptides, were not efficiently depleted by CroFab®. These results therefore provide a comprehensive catalog of the venom compounds present in C. v. viridis venom and new molecular insight into the potential efficacy of CroFab® against human envenomations by one of the most widely distributed rattlesnake species in North America. Biological significance Comparative proteomic analysis of venoms of neonate and adult Prairie Rattlesnake (Crotalus viridis viridis) from a discrete population in Colorado revealed a novel pattern of ontogenetic shifts in toxin composition for viperid snakes. The observed stage-dependent decrease of the relative content of disintegrins, catalytically active D49-PLA2s, L-amino acid oxidase, and SVMPs, and the concomitant increase of the relative abundance of paralytic small basic myotoxins and ohanin-like toxin, and hemostasis-disrupting serine Proteinases, may represent an age-dependent strategy for securing prey and avoiding injury as the snake switches from small ectothermic prey and newborn rodents to larger endothermic prey. Such age-dependent shifts in venom composition may be relevant for antivenom efficacy and treatment of snakebite. However, applying a second-generation antivenomics approach, we show that CroFab®, developed against venom of three Crotalus and one Agkistrodon species, efficiently immunodepleted many, but not all, of the major compounds present in neonate and adult C. v. viridis venoms.
Libia Sanz - One of the best experts on this subject based on the ideXlab platform.
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venomics of the duvernoy s gland secretion of the false coral snake rhinobothryum bovallii andersson 1916 and assessment of venom lethality towards synapsid and diapsid animal models
Journal of Proteomics, 2020Co-Authors: Juan J. Calvete, Bruno Lomonte, Libia Sanz, Fabian Bonilla, Sofia Granadosmartinez, Mahmood SasaAbstract:Abstract The Duvernoy's gland Secretory proteome of the false coral snake Rhinobothryum bovallii (Costa Rica), unveiled applying bottom-up venomics, comprises a handful of toxins belonging to only three Protein families, three-finger toxin (3FTx), Cysteine-Rich Secretory Protein (CRISP), and snake venom metalloprotease (PIII-SVMP). Except for small differences in the relative abundance of the PIII-SVMPs, which may be due to individual variability, no evidence of geographic variability or ontogenetic changes was found among the venom proteomes of the juvenile and adult R. bovallii snakes sampled. Major monomeric (86.5%mol) and minor dimeric (2.8%mol) 3FTxs dominate the toxin arsenal of the Costa Rican false coral snake. The remaining 10.7% of the venom proteome comprises CRISP (8.2%) and PIII-SVMP (2.4%) molecules. In vivo lethality assays showed that R. bovallii produces venom that is non-toxic towards mammalian prey, and which exerts a different toxic effect on domestic chicken chicks and baby green iguana. Toxicovenomic analysis of R. bovallii venom in the iguana model identified two 3FTx RP-HPLC fractions that faithfully mimicked the irreversible immobilizing effect of the whole venom. Biological significance With more than 2200 species in family Colubridae (sensu lato), rear-fanged snakes comprise approximately two-thirds of the extant species of advanced snakes. Snakebites from venomous snakes that are of medical concern are predominantly from front-fanged snakes of families Viperidae and Elapidae. On the other hand, rear-fanged snakes have been conventionally considered non-venomous, and thus their venoms have remained a largely untapped area of venomics. However, increasing documentation of life-threadening, even fatal, envenomings from rear-fanged snakes has sparked interest in their venoms. Appying bottom-up venomics we have revealed that the Duvernoy's gland Secretory proteome of R. bovallii comprises a handful of toxins belonging to only three Protein families, with slow-acting three-finger toxins (3FTx) that are non-toxic towards mammalian prey and show preference towards diapsid taxa representing the dominant structural and functional Proteins. Our work documents for the first time 3FTxs exerting different effect in an avian model than in a reptile model. Besides, the 3FTx fractions that faithfully mimicked the irreversible iguana-immobilizing effect of the whole venom were identified through toxicovenomic analysis of R. bovallii venom on Iguana iguana. Our work underscores the importance of using biologically-relevant animal toxicity models for investigating the biological roles of venoms in an evolutionary-ecological context.
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Immunoaffinity chromatography-based antivenomic analysis of the immunoreactivity of polyspecific and monospecific antivenoms towards the venom of L. muta muta from Colombia.
2017Co-Authors: Marvin Madrigal, Libia Sanz, José María Gutiérrez, Davinia Pla, Elexandra Barboza, Cynthia Arroyo-portilla, Carlos Corrêa-netto, Alberto Alape-girón, Marietta Flores-díaz, Juan J. CalveteAbstract:Panels display reverse-phase separations of whole venom components, and non-retained (A, C, E, G, and I) and the retained (B, D, F, H, and J) fractions recovered, respectively, from the affinity columns of immobilized BCL, BL, AL, AB, and AC antivenoms. Panels K and L, non-retained and retained venom fractions by immobilized equine control immunoglobulins. CRISP, Cysteine-Rich Secretory Protein. Other Protein acronyms as in the legend of Fig 2.
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Immunoaffinity chromatography-based antivenomic analysis of the immunoreactivity of polyspecific and monospecific antivenoms towards the venom of L. muta muta from Cascalheira (Brazil).
2017Co-Authors: Marvin Madrigal, Libia Sanz, José María Gutiérrez, Davinia Pla, Elexandra Barboza, Cynthia Arroyo-portilla, Carlos Corrêa-netto, Alberto Alape-girón, Marietta Flores-díaz, Juan J. CalveteAbstract:Panels display reverse-phase separations of whole venom components, and non-retained (A, C, E, G, and I) and the retained (B, D, F, H, and J) fractions recovered, respectively, from the affinity columns of immobilized BCL, BL, L, B, and C antivenoms. Panels K and L, non-retained and retained venom fractions by immobilized equine control immunoglobulins. CRISP, Cysteine-Rich Secretory Protein; other acronyms as in the legend of Fig 2.
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comparative venomics of the prairie rattlesnake crotalus viridis viridis from colorado identification of a novel pattern of ontogenetic changes in venom composition and assessment of the immunoreactivity of the commercial antivenom crofab
Journal of Proteomics, 2015Co-Authors: Juan J. Calvete, Libia Sanz, Anthony J Saviola, Todd A Castoe, Stephen P MackessyAbstract:Abstract Here we describe and compare the venomic and antivenomic characteristics of both neonate and adult Prairie Rattlesnake (Crotalus viridis viridis) venoms. Although both neonate and adult venoms contain unique components, similarities among Protein family content were seen. Both neonate and adult venoms consisted of myotoxin, bradykinin-potentiating peptide (BPP), phospholipase A2 (PLA2), Zn2 +-dependent metalloProteinase (SVMP), serine Proteinase, L-amino acid oxidase (LAAO), Cysteine-Rich Secretory Protein (CRISP) and disintegrin families. Quantitative differences, however, were observed, with venoms of adults containing significantly higher concentrations of the non-enzymatic toxic compounds and venoms of neonates containing higher concentrations of pre-digestive enzymatic Proteins such as SVMPs. To assess the relevance of this venom variation in the context of snakebite and snakebite treatment, we tested the efficacy of the common antivenom CroFab® for recognition of both adult and neonate venoms in vitro. This comparison revealed that many of the major Protein families (SVMPs, CRISP, PLA2, serine proteases, and LAAO) in both neonate and adult venoms were immunodepleted by the antivenom, whereas myotoxins, one of the major toxic components of C. v. viridis venom, in addition to many of the small peptides, were not efficiently depleted by CroFab®. These results therefore provide a comprehensive catalog of the venom compounds present in C. v. viridis venom and new molecular insight into the potential efficacy of CroFab® against human envenomations by one of the most widely distributed rattlesnake species in North America. Biological significance Comparative proteomic analysis of venoms of neonate and adult Prairie Rattlesnake (Crotalus viridis viridis) from a discrete population in Colorado revealed a novel pattern of ontogenetic shifts in toxin composition for viperid snakes. The observed stage-dependent decrease of the relative content of disintegrins, catalytically active D49-PLA2s, L-amino acid oxidase, and SVMPs, and the concomitant increase of the relative abundance of paralytic small basic myotoxins and ohanin-like toxin, and hemostasis-disrupting serine Proteinases, may represent an age-dependent strategy for securing prey and avoiding injury as the snake switches from small ectothermic prey and newborn rodents to larger endothermic prey. Such age-dependent shifts in venom composition may be relevant for antivenom efficacy and treatment of snakebite. However, applying a second-generation antivenomics approach, we show that CroFab®, developed against venom of three Crotalus and one Agkistrodon species, efficiently immunodepleted many, but not all, of the major compounds present in neonate and adult C. v. viridis venoms.
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two color morphs of the pelagic yellow bellied sea snake pelamis platura from different locations of costa rica snake venomics toxicity and neutralization by antivenom
Journal of Proteomics, 2014Co-Authors: Bruno Lomonte, Libia Sanz, Davinia Pla, Mahmood Sasa, Wanchih Tsai, Alejandro Solorzano, Juan Manuel Urenadiaz, Maria Laura Fernandezmontes, Diana Moraobando, José María GutiérrezAbstract:Abstract The yellow-bellied sea snake, Pelamis platura , is the most broadly distributed snake species. Despite being endowed with a highly lethal venom, a proteomic analysis of its toxin composition was unavailable. The venoms of specimens collected in Golfo de Papagayo and Golfo Dulce (Costa Rica), where two distinctive color morphs occur, were chromatographically compared. The latter inhabits a fjord-like gulf where the transit of oceanic sea snakes into and from the basin is restricted, thus possibly affecting gene flow. RP-HPLC evidenced a conserved venom Protein profile in both populations, despite their divergent color phenotypes. Following a trend observed in other sea snakes, P. platura venom is relatively simple, being composed of Proteins of the three-finger toxin (3FTx), phospholipase A 2 (PLA 2 ), Cysteine-Rich Secretory Protein (CRISP), 5′-nucleotidase, and metalloProteinase families. The first three groups represent 49.9%, 32.9%, and 9.1% of total venom Protein, respectively. The most abundant component (~ 26%) is pelamitoxin ( P62388 ), a short-chain 3FTx, followed by a major basic PLA 2 (~ 20%) and a group of three isoforms of CRISPs (~ 9%). Whereas isolated pelamitoxin was highly lethal to mice, neither the PLA 2 nor the CRISP fraction caused death. However, the PLA 2 rapidly increased plasma creatine kinase activity after intramuscular injection, indicating its myotoxic action. Differing from myotoxic PLA 2 s of viperids, this PLA 2 was not cytolytic to murine myogenic cells in vitro , suggesting possible differences in its mechanism of action. The median lethal dose (LD 50 ) estimates for P. platura crude venom in mice and in three species of fishes did not differ significantly. The sea snake antivenom manufactured by CSL Ltd. (Australia), which uses Enhydrina schistosa as immunogen, cross-recognized the three major components of P. platura venom and, accordingly, neutralized the lethal activity of crude venom and pelamitoxin, therefore being of potential usefulness in the treatment of envenomations by this species. Biological significance Integrative analyses of animal venoms that combine the power of proteomics (venomics) with the characterization of their functional and immunological properties are significantly expanding knowledge on these remarkable bioweapons, both from a basic and a medical perspective. Costa Rica harbors a unique population of the yellow-bellied sea snake, Pelamis platura , that is restricted to a fjord-like gulf (Golfo Dulce). This population differs markedly from oceanic populations found elsewhere along the Pacific coast of this country, by presenting a patternless bright yellow coloration, instead of the typical bicolored or tricolored pattern of this species. It has been suggested that the dominance of this yellow-morph in Golfo Dulce might reflect gene flow restrictions, caused by the oceanographic conditions at this location. The present study demonstrates that the remarkable phenotypic variation between the two color morphs inhabiting Golfo Dulce and Golfo de Papagayo, respectively, is not associated with differences in the expression of venom components, as shown by their conserved RP-HPLC profiles. Proteomic analysis revealed the relatively simple toxin composition of P. platura venom, which contains three predominant types of Proteins: three-finger toxins (Protein abundance: 49.9%), phospholipases A 2 (32.9%), and Cysteine-Rich Secretory Proteins (9.1%), together with few minor components. Further, the involvement of these most abundant Proteins in the toxic effects of the venom, and their cross-recognition and neutralization by a sea snake antivenom produced against the venom of Enhydrina schistosa , were analyzed.
Pier Giorgio Righetti - One of the best experts on this subject based on the ideXlab platform.
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exploring the venom proteome of the western diamondback rattlesnake crotalus atrox via snake venomics and combinatorial peptide ligand library approaches
Journal of Proteome Research, 2009Co-Authors: Juan J. Calvete, Elisa Fasoli, Egisto Boschetti, Libia Sanz, Pier Giorgio RighettiAbstract:We report the proteomic characterization of the venom of the medically important North American western diamondback rattlesnake, Crotalus atrox, using two complementary approaches: snake venomics (to gain an insight of the overall venom proteome), and two solid-phase combinatorial peptide ligand libraries (CPLL), followed by 2D electrophoresis and mass spectrometric characterization of in-gel digested Protein bands (to capture and “amplify“ low-abundance Proteins). The venomics approach revealed ∼24 distinct Proteins belonging to 2 major Protein families (snake venom metalloProteinases, SVMP, and serine Proteinases), which represent 69.5% of the total venom Proteins, 4 medium abundance families (medium-size disintegrin, PLA2, Cysteine-Rich Secretory Protein, and l-amino acid oxidase) amounting to 25.8% of the venom Proteins, and 3 minor Protein families (vasoactive peptides, endogenous inhibitor of SVMP, and C-type lectin-like). This toxin profile potentially explains the cytotoxic, myotoxic, hemotoxic, a...
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exploring the venom proteome of the western diamondback rattlesnake crotalus atrox via snake venomics and combinatorial peptide ligand library approaches
Journal of Proteome Research, 2009Co-Authors: Juan J. Calvete, Elisa Fasoli, Egisto Boschetti, Libia Sanz, Pier Giorgio RighettiAbstract:We report the proteomic characterization of the venom of the medically important North American western diamondback rattlesnake, Crotalus atrox, using two complementary approaches: snake venomics (to gain an insight of the overall venom proteome), and two solid-phase combinatorial peptide ligand libraries (CPLL), followed by 2D electrophoresis and mass spectrometric characterization of in-gel digested Protein bands (to capture and "amplify" low-abundance Proteins). The venomics approach revealed approximately 24 distinct Proteins belonging to 2 major Protein families (snake venom metalloProteinases, SVMP, and serine Proteinases), which represent 69.5% of the total venom Proteins, 4 medium abundance families (medium-size disintegrin, PLA(2), Cysteine-Rich Secretory Protein, and l-amino acid oxidase) amounting to 25.8% of the venom Proteins, and 3 minor Protein families (vasoactive peptides, endogenous inhibitor of SVMP, and C-type lectin-like). This toxin profile potentially explains the cytotoxic, myotoxic, hemotoxic, and hemorrhagic effects evoked by C. atrox envenomation. Further, our results showing that C. atrox exhibits a similar level of venom variation as Sistrurus miliarius points to a "diversity gain" scenario in the lineage leading to the Sistrurus catenatus taxa. On the other hand, the two combinatorial hexapeptide libraries captured distinct sets of Proteins. Although the CPLL-treated samples did not retain a representative venom proteome, Protein spots barely, or not at all, detectable in the whole venom were enriched in the two CPLL-treated samples. The amplified low copy number C. atrox venom Proteins comprised a C-type lectin-like Protein, several PLA(2) molecules, PIII-SVMP isoforms, glutaminyl cyclase isoforms, and a 2-cys peroxiredoxin highly conserved across the animal kingdom. Peroxiredoxin and glutaminyl cyclase may participate, respectively, in redox processes leading to the structural/functional diversification of toxins, and in the N-terminal pyrrolidone carboxylic acid formation required in the maturation of bioactive peptides such as bradykinin-potentiating peptides and endogenous inhibitors of metalloproteases. Our findings underscore the usefulness of combinatorial peptide libraries as powerful tools for mining below the tip of the iceberg, complementing thereby the data gained using the snake venomics protocol toward a complete visualization of the venom proteome.
Bruno Lomonte - One of the best experts on this subject based on the ideXlab platform.
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venomics of the duvernoy s gland secretion of the false coral snake rhinobothryum bovallii andersson 1916 and assessment of venom lethality towards synapsid and diapsid animal models
Journal of Proteomics, 2020Co-Authors: Juan J. Calvete, Bruno Lomonte, Libia Sanz, Fabian Bonilla, Sofia Granadosmartinez, Mahmood SasaAbstract:Abstract The Duvernoy's gland Secretory proteome of the false coral snake Rhinobothryum bovallii (Costa Rica), unveiled applying bottom-up venomics, comprises a handful of toxins belonging to only three Protein families, three-finger toxin (3FTx), Cysteine-Rich Secretory Protein (CRISP), and snake venom metalloprotease (PIII-SVMP). Except for small differences in the relative abundance of the PIII-SVMPs, which may be due to individual variability, no evidence of geographic variability or ontogenetic changes was found among the venom proteomes of the juvenile and adult R. bovallii snakes sampled. Major monomeric (86.5%mol) and minor dimeric (2.8%mol) 3FTxs dominate the toxin arsenal of the Costa Rican false coral snake. The remaining 10.7% of the venom proteome comprises CRISP (8.2%) and PIII-SVMP (2.4%) molecules. In vivo lethality assays showed that R. bovallii produces venom that is non-toxic towards mammalian prey, and which exerts a different toxic effect on domestic chicken chicks and baby green iguana. Toxicovenomic analysis of R. bovallii venom in the iguana model identified two 3FTx RP-HPLC fractions that faithfully mimicked the irreversible immobilizing effect of the whole venom. Biological significance With more than 2200 species in family Colubridae (sensu lato), rear-fanged snakes comprise approximately two-thirds of the extant species of advanced snakes. Snakebites from venomous snakes that are of medical concern are predominantly from front-fanged snakes of families Viperidae and Elapidae. On the other hand, rear-fanged snakes have been conventionally considered non-venomous, and thus their venoms have remained a largely untapped area of venomics. However, increasing documentation of life-threadening, even fatal, envenomings from rear-fanged snakes has sparked interest in their venoms. Appying bottom-up venomics we have revealed that the Duvernoy's gland Secretory proteome of R. bovallii comprises a handful of toxins belonging to only three Protein families, with slow-acting three-finger toxins (3FTx) that are non-toxic towards mammalian prey and show preference towards diapsid taxa representing the dominant structural and functional Proteins. Our work documents for the first time 3FTxs exerting different effect in an avian model than in a reptile model. Besides, the 3FTx fractions that faithfully mimicked the irreversible iguana-immobilizing effect of the whole venom were identified through toxicovenomic analysis of R. bovallii venom on Iguana iguana. Our work underscores the importance of using biologically-relevant animal toxicity models for investigating the biological roles of venoms in an evolutionary-ecological context.
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Snake venomics of monocled cobra (Naja kaouthia) and investigation of human IgG response against venom toxins
Toxicon, 2015Co-Authors: Andreas Hougaard Laustsen, Arne R. Rasmussen, Christina Milbo, Brian Lohse, Julian Fernandez, Bruno LomonteAbstract:The venom proteome of the monocled cobra, Naja kaouthia, from Thailand, was characterized by RP-HPLC, SDS-PAGE, and MALDI-TOF-TOF analyses, yielding 38 different Proteins that were either identified or assigned to families. Estimation of relative Protein abundances revealed that venom is dominated by three-finger toxins (77.5%; including 24.3% cytotoxins and 53.2% neurotoxins) and phospholipases A2 (13.5%). It also contains lower proportions of components belonging to nerve growth factor, ohanin/vespryn, Cysteine-Rich Secretory Protein, C-type lectin/lectin-like, nucleotidase, phosphodiesterase, metalloProteinase, l-amino acid oxidase, cobra venom factor, and cytidyltransferase Protein families. Small amounts of three nucleosides were also evidenced: adenosine, guanosine, and inosine. The most relevant lethal components, categorized by means of a 'toxicity score', were α-neurotoxins, followed by cytotoxins/cardiotoxins. IgGs isolated from a person who had repeatedly self-immunized with a variety of snake venoms were immunoprofiled by ELISA against all venom fractions. Stronger responses against larger toxins, but lower against the most critical α-neurotoxins were obtained. As expected, no neutralization potential against N. kaouthia venom was therefore detected. Combined, our results display a high level of venom complexity, unveil the most relevant toxins to be neutralized, and provide prospects of discovering human IgGs with toxin neutralizing abilities through use of phage display screening.
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two color morphs of the pelagic yellow bellied sea snake pelamis platura from different locations of costa rica snake venomics toxicity and neutralization by antivenom
Journal of Proteomics, 2014Co-Authors: Bruno Lomonte, Libia Sanz, Davinia Pla, Mahmood Sasa, Wanchih Tsai, Alejandro Solorzano, Juan Manuel Urenadiaz, Maria Laura Fernandezmontes, Diana Moraobando, José María GutiérrezAbstract:Abstract The yellow-bellied sea snake, Pelamis platura , is the most broadly distributed snake species. Despite being endowed with a highly lethal venom, a proteomic analysis of its toxin composition was unavailable. The venoms of specimens collected in Golfo de Papagayo and Golfo Dulce (Costa Rica), where two distinctive color morphs occur, were chromatographically compared. The latter inhabits a fjord-like gulf where the transit of oceanic sea snakes into and from the basin is restricted, thus possibly affecting gene flow. RP-HPLC evidenced a conserved venom Protein profile in both populations, despite their divergent color phenotypes. Following a trend observed in other sea snakes, P. platura venom is relatively simple, being composed of Proteins of the three-finger toxin (3FTx), phospholipase A 2 (PLA 2 ), Cysteine-Rich Secretory Protein (CRISP), 5′-nucleotidase, and metalloProteinase families. The first three groups represent 49.9%, 32.9%, and 9.1% of total venom Protein, respectively. The most abundant component (~ 26%) is pelamitoxin ( P62388 ), a short-chain 3FTx, followed by a major basic PLA 2 (~ 20%) and a group of three isoforms of CRISPs (~ 9%). Whereas isolated pelamitoxin was highly lethal to mice, neither the PLA 2 nor the CRISP fraction caused death. However, the PLA 2 rapidly increased plasma creatine kinase activity after intramuscular injection, indicating its myotoxic action. Differing from myotoxic PLA 2 s of viperids, this PLA 2 was not cytolytic to murine myogenic cells in vitro , suggesting possible differences in its mechanism of action. The median lethal dose (LD 50 ) estimates for P. platura crude venom in mice and in three species of fishes did not differ significantly. The sea snake antivenom manufactured by CSL Ltd. (Australia), which uses Enhydrina schistosa as immunogen, cross-recognized the three major components of P. platura venom and, accordingly, neutralized the lethal activity of crude venom and pelamitoxin, therefore being of potential usefulness in the treatment of envenomations by this species. Biological significance Integrative analyses of animal venoms that combine the power of proteomics (venomics) with the characterization of their functional and immunological properties are significantly expanding knowledge on these remarkable bioweapons, both from a basic and a medical perspective. Costa Rica harbors a unique population of the yellow-bellied sea snake, Pelamis platura , that is restricted to a fjord-like gulf (Golfo Dulce). This population differs markedly from oceanic populations found elsewhere along the Pacific coast of this country, by presenting a patternless bright yellow coloration, instead of the typical bicolored or tricolored pattern of this species. It has been suggested that the dominance of this yellow-morph in Golfo Dulce might reflect gene flow restrictions, caused by the oceanographic conditions at this location. The present study demonstrates that the remarkable phenotypic variation between the two color morphs inhabiting Golfo Dulce and Golfo de Papagayo, respectively, is not associated with differences in the expression of venom components, as shown by their conserved RP-HPLC profiles. Proteomic analysis revealed the relatively simple toxin composition of P. platura venom, which contains three predominant types of Proteins: three-finger toxins (Protein abundance: 49.9%), phospholipases A 2 (32.9%), and Cysteine-Rich Secretory Proteins (9.1%), together with few minor components. Further, the involvement of these most abundant Proteins in the toxic effects of the venom, and their cross-recognition and neutralization by a sea snake antivenom produced against the venom of Enhydrina schistosa , were analyzed.
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venomics of the duvernoy s gland secretion of the false coral snake rhinobothryum bovallii andersson 1916 and assessment of venom lethality towards synapsid and diapsid animal models
Journal of Proteomics, 2020Co-Authors: Juan J. Calvete, Bruno Lomonte, Libia Sanz, Fabian Bonilla, Sofia Granadosmartinez, Mahmood SasaAbstract:Abstract The Duvernoy's gland Secretory proteome of the false coral snake Rhinobothryum bovallii (Costa Rica), unveiled applying bottom-up venomics, comprises a handful of toxins belonging to only three Protein families, three-finger toxin (3FTx), Cysteine-Rich Secretory Protein (CRISP), and snake venom metalloprotease (PIII-SVMP). Except for small differences in the relative abundance of the PIII-SVMPs, which may be due to individual variability, no evidence of geographic variability or ontogenetic changes was found among the venom proteomes of the juvenile and adult R. bovallii snakes sampled. Major monomeric (86.5%mol) and minor dimeric (2.8%mol) 3FTxs dominate the toxin arsenal of the Costa Rican false coral snake. The remaining 10.7% of the venom proteome comprises CRISP (8.2%) and PIII-SVMP (2.4%) molecules. In vivo lethality assays showed that R. bovallii produces venom that is non-toxic towards mammalian prey, and which exerts a different toxic effect on domestic chicken chicks and baby green iguana. Toxicovenomic analysis of R. bovallii venom in the iguana model identified two 3FTx RP-HPLC fractions that faithfully mimicked the irreversible immobilizing effect of the whole venom. Biological significance With more than 2200 species in family Colubridae (sensu lato), rear-fanged snakes comprise approximately two-thirds of the extant species of advanced snakes. Snakebites from venomous snakes that are of medical concern are predominantly from front-fanged snakes of families Viperidae and Elapidae. On the other hand, rear-fanged snakes have been conventionally considered non-venomous, and thus their venoms have remained a largely untapped area of venomics. However, increasing documentation of life-threadening, even fatal, envenomings from rear-fanged snakes has sparked interest in their venoms. Appying bottom-up venomics we have revealed that the Duvernoy's gland Secretory proteome of R. bovallii comprises a handful of toxins belonging to only three Protein families, with slow-acting three-finger toxins (3FTx) that are non-toxic towards mammalian prey and show preference towards diapsid taxa representing the dominant structural and functional Proteins. Our work documents for the first time 3FTxs exerting different effect in an avian model than in a reptile model. Besides, the 3FTx fractions that faithfully mimicked the irreversible iguana-immobilizing effect of the whole venom were identified through toxicovenomic analysis of R. bovallii venom on Iguana iguana. Our work underscores the importance of using biologically-relevant animal toxicity models for investigating the biological roles of venoms in an evolutionary-ecological context.
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two color morphs of the pelagic yellow bellied sea snake pelamis platura from different locations of costa rica snake venomics toxicity and neutralization by antivenom
Journal of Proteomics, 2014Co-Authors: Bruno Lomonte, Libia Sanz, Davinia Pla, Mahmood Sasa, Wanchih Tsai, Alejandro Solorzano, Juan Manuel Urenadiaz, Maria Laura Fernandezmontes, Diana Moraobando, José María GutiérrezAbstract:Abstract The yellow-bellied sea snake, Pelamis platura , is the most broadly distributed snake species. Despite being endowed with a highly lethal venom, a proteomic analysis of its toxin composition was unavailable. The venoms of specimens collected in Golfo de Papagayo and Golfo Dulce (Costa Rica), where two distinctive color morphs occur, were chromatographically compared. The latter inhabits a fjord-like gulf where the transit of oceanic sea snakes into and from the basin is restricted, thus possibly affecting gene flow. RP-HPLC evidenced a conserved venom Protein profile in both populations, despite their divergent color phenotypes. Following a trend observed in other sea snakes, P. platura venom is relatively simple, being composed of Proteins of the three-finger toxin (3FTx), phospholipase A 2 (PLA 2 ), Cysteine-Rich Secretory Protein (CRISP), 5′-nucleotidase, and metalloProteinase families. The first three groups represent 49.9%, 32.9%, and 9.1% of total venom Protein, respectively. The most abundant component (~ 26%) is pelamitoxin ( P62388 ), a short-chain 3FTx, followed by a major basic PLA 2 (~ 20%) and a group of three isoforms of CRISPs (~ 9%). Whereas isolated pelamitoxin was highly lethal to mice, neither the PLA 2 nor the CRISP fraction caused death. However, the PLA 2 rapidly increased plasma creatine kinase activity after intramuscular injection, indicating its myotoxic action. Differing from myotoxic PLA 2 s of viperids, this PLA 2 was not cytolytic to murine myogenic cells in vitro , suggesting possible differences in its mechanism of action. The median lethal dose (LD 50 ) estimates for P. platura crude venom in mice and in three species of fishes did not differ significantly. The sea snake antivenom manufactured by CSL Ltd. (Australia), which uses Enhydrina schistosa as immunogen, cross-recognized the three major components of P. platura venom and, accordingly, neutralized the lethal activity of crude venom and pelamitoxin, therefore being of potential usefulness in the treatment of envenomations by this species. Biological significance Integrative analyses of animal venoms that combine the power of proteomics (venomics) with the characterization of their functional and immunological properties are significantly expanding knowledge on these remarkable bioweapons, both from a basic and a medical perspective. Costa Rica harbors a unique population of the yellow-bellied sea snake, Pelamis platura , that is restricted to a fjord-like gulf (Golfo Dulce). This population differs markedly from oceanic populations found elsewhere along the Pacific coast of this country, by presenting a patternless bright yellow coloration, instead of the typical bicolored or tricolored pattern of this species. It has been suggested that the dominance of this yellow-morph in Golfo Dulce might reflect gene flow restrictions, caused by the oceanographic conditions at this location. The present study demonstrates that the remarkable phenotypic variation between the two color morphs inhabiting Golfo Dulce and Golfo de Papagayo, respectively, is not associated with differences in the expression of venom components, as shown by their conserved RP-HPLC profiles. Proteomic analysis revealed the relatively simple toxin composition of P. platura venom, which contains three predominant types of Proteins: three-finger toxins (Protein abundance: 49.9%), phospholipases A 2 (32.9%), and Cysteine-Rich Secretory Proteins (9.1%), together with few minor components. Further, the involvement of these most abundant Proteins in the toxic effects of the venom, and their cross-recognition and neutralization by a sea snake antivenom produced against the venom of Enhydrina schistosa , were analyzed.
