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Sample records for fish venoms

  1. Bioactive Components in Fish Venoms

    PubMed Central

    Ziegman, Rebekah; Alewood, Paul

    2015-01-01

    Animal venoms are widely recognized excellent resources for the discovery of novel drug leads and physiological tools. Most are comprised of a large number of components, of which the enzymes, small peptides, and proteins are studied for their important bioactivities. However, in spite of there being over 2000 venomous fish species, piscine venoms have been relatively underrepresented in the literature thus far. Most studies have explored whole or partially fractioned venom, revealing broad pharmacology, which includes cardiovascular, neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been isolated from scorpaenoid fish. These form pores in cell membranes, resulting in cell death and creating a cascade of reactions that result in many, but not all, of the physiological symptoms observed from envenomation. Additionally, Natterins, a novel family of toxins possessing kininogenase activity have been found in toadfish venom. A variety of smaller protein toxins, as well as a small number of peptides, enzymes, and non-proteinaceous molecules have also been isolated from a range of fish venoms, but most remain poorly characterized. Many other bioactive fish venom components remain to be discovered and investigated. These represent an untapped treasure of potentially useful molecules. PMID:25941767

  2. The pharmacological activity of fish venoms.

    PubMed

    Church, Jarrod E; Hodgson, Wayne C

    2002-08-01

    Venomous creatures have been the source of much recent research in the effort to find novel physiological tools and pharmaceuticals. However, due to the technical difficulties with obtaining and storing venom extracts, the venoms of marine animals, particularly fish, remain a largely untapped source of novel compounds. The most potent effects of piscine venoms are on the cardiovascular system. All piscine venoms produce profound cardiovascular changes, both in vitro and in vivo, including the release of nitric oxide from endothelial cells, smooth muscle contraction, and differing effects on atria. Although there is a complex balance between different components of the venom response, similarities exist between the responses to the venoms of all species of fish. In addition to their cardiovascular effects, piscine venoms possess neuromuscular activity. Once again, the activities of most piscine venoms are very similar, usually consisting of a depolarising action on both nerve and muscle cells. Most piscine venoms have potent cytolytic activity, and it seems likely that this activity is the mechanism behind many of their cardiovascular and neuromuscular effects. Piscine venoms all seem to share similar activity, probably as a result of evolving for a common purpose, and cross-reactivity with stonefish antivenom, both functionally in experimental models and in Western immunoblotting analysis, suggesting that piscine venoms may also possess structural similarities in addition to their functional similarities.

  3. Angiotensin converting enzymes in fish venom.

    PubMed

    Dos Santos, Dávida Maria Ribeiro Cardoso; de Souza, Cledson Barros; Pereira, Hugo Juarez Vieira

    2017-06-01

    Animal venoms are multifaceted mixtures, including proteins, peptides and enzymes produced by animals in defense, predation and digestion. These molecules have been investigated concerning their molecular mechanisms associated and possible pharmacological applications. Thalassophryne nattereri is a small venomous fish inhabiting the northern and northeastern coast of Brazil, and represents a relatively frequent cause of injuries. Its venom causes severe inflammatory response followed frequently by the necrosis of the affected area. Scorpaena plumieri is the most venomous fish in the Brazilian fauna and is responsible for relatively frequent accidents involving anglers and bathers. In humans, its venom causes edema, erythema, ecchymoses, nausea, vomiting, and syncope. Recently, the presence of a type of angiotensin converting enzyme (ACE) activity in the venom of Thalassophryne nattereri and Scorpaena plumieri, endemic fishes in northeastern coast of Brazil, has been described. The ACE converts angiotensin I (Ang I) into angiotensin II (Ang II) and inactivates bradykinin, there by regulating blood pressure and electrolyte homeostasis, however, their function in these venoms remains an unknown. This article provides an overview of the current knowledge on ACE in the venoms of Thalassophryne nattereri and Scorpaena plumier.

  4. Evolution of Venomous Cartilaginous and Ray-Finned Fishes.

    PubMed

    Smith, W Leo; Stern, Jennifer H; Girard, Matthew G; Davis, Matthew P

    2016-11-01

    Venom and its associated delivery systems have evolved in numerous animal groups ranging from jellyfishes to spiders, lizards, shrews, and the male platypus. Building off new data and previously published anatomical and molecular studies, we explore the evolution of and variation within venomous fishes. We show the results of the first multi-locus, ordinal-level phylogenetic analysis of cartilaginous (Chondrichthyes) and ray-finned (Actinopterygii) fishes that hypothesizes 18 independent evolutions of this specialization. Ancestral-states reconstruction indicates that among the 2386-2962 extant venomous fishes, envenomed structures have evolved four times in cartilaginous fishes, once in eels (Anguilliformes), once in catfishes (Siluriformes), and 12 times in spiny-rayed fishes (Acanthomorpha). From our anatomical studies and phylogenetic reconstruction, we show that dorsal spines are the most common envenomed structures (∼95% of venomous fish species and 15 independent evolutions). In addition to envenomed spines, fishes have also evolved venomous fangs (2% of venomous fish species, two independent evolutions), cleithral spines (2% of venomous fish species, one independent evolution), and opercular or subopercular spines (1% of venomous fish species, three independent evolutions).

  5. Behavior, Ecology and Toxicity of Venomous Marine Fishes.

    DTIC Science & Technology

    1977-12-31

    u ltrastructure of the venom apparatus of the stingrays and scorpion fishes ’~~nd~ .. I# )”the chemistry and pharmacolo~~~~~~M~~ ~~~~~~ o of stingray

  6. Biological properties of a crude venom extract from the greater weever fish Trachinus draco.

    PubMed

    Chhatwal, I; Dreyer, F

    1992-01-01

    Crude venom of the greater weever fish, Trachinus draco was analyzed to assess its toxicity, stability and biological properties. The best yield of venom was obtained by extraction in physiological saline of the whole venom apparatus of the fish which were shock-frozen and stored at -70 degrees C. This extract had a mouse i.v. minimum lethal dose of 1.8 micrograms protein per gram mouse and a total of 61,000 minimum lethal doses were obtained from venom apparatus of one fish. The lethal activity was unstable at room temperature especially at lower protein concentrations. Stability was achieved either by storing the extract at -70 degrees C or by precipitation with ammonium sulfate at 50% saturation. Toxicity of the crude venom was abolished by trypsin treatment. The crude venom did not possess any proteolytic or histamine-releasing activities. The venom caused an outflow of tetraphenylphosphonium from preloaded rat brain particles in a concentration-dependent manner. Like toxicity, this effect was also abolished by trypsin treatment or by keeping the venom at higher temperatures. The crude venom also possessed hemolytic activity with an EC50 for rabbit erythrocytes of 75 ng/ml venom protein. The hemolytic activity was also sensitive to heat and proteolytic treatment. Rabbit erythrocytes were most sensitive to venom followed by rat erythrocytes. Mouse and cattle erythrocytes were only slightly sensitive, whereas human, chicken and guinea pig erythrocytes were totally resistant.

  7. A ray of venom: Combined proteomic and transcriptomic investigation of fish venom composition using barb tissue from the blue-spotted stingray (Neotrygon kuhlii).

    PubMed

    Baumann, Kate; Casewell, Nicholas R; Ali, Syed A; Jackson, Timothy N W; Vetter, Irina; Dobson, James S; Cutmore, Scott C; Nouwens, Amanda; Lavergne, Vincent; Fry, Bryan G

    2014-09-23

    Fish venoms remain almost completely unstudied despite the large number of species. In part this is due to the inherent nature of fish venoms, in that they are highly sensitive to heat, pH, lyophilisation, storage and repeated freeze-thawing. They are also heavily contaminated with mucus, which makes proteomic study difficult. Here we describe a novel protein-handling protocol to remove mucus contamination, utilising ammonium sulphate and acetone precipitation. We validated this approach using barb venom gland tissue protein extract from the blue-spotted stingray Neotrygon kuhlii. We analysed the protein extract using 1D and 2D gels with LC-MS/MS sequencing. Protein annotation was underpinned by a venom gland transcriptome. The composition of our N. kuhlii venom sample revealed a variety of protein types that are completely novel to animal venom systems. Notably, none of the detected proteins exhibited similarity to the few toxin components previously characterised from fish venoms, including those found in other stingrays. Putative venom toxins identified here included cystatin, peroxiredoxin and galectin. Our study represents the first combined survey of gene and protein composition from the venom apparatus of any fish and our novel protein handling method will aid the future characterisation of toxins from other unstudied venomous fish lineages. These results show an efficient manner for removing mucus from fish venoms. These results are the first insights into the evolution of proteins present on stingrayvenom barbs. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. [Poisoning with weever fish venom: a case report].

    PubMed

    Łopaciński, Bogdan; Bak, Marek; Fiszer, Marta; Czerniak, Paweł; Krakowiak, Anna

    2009-01-01

    Poland's access to the EU causes that there is the risk of poisoning from sources outside Poland. This is confirmed by the case reported below. The Weeverfish Trachinus draco lives in the coastal waters of West Africa and Europe (including those of the Mediterranean Sea) and belongs to the most poisonous fish species. The venom of Trachinus draco contains proteins that cause cellular membrane depolarisation, and haemolysis. A 35-yr. man was admitted to the Toxicological Department of the Nofer Institute of Occupational Medicine for symptoms, such as: a strong pain, swelling and reddening of the left leg, that had appeared after contact with an unidentified fish when he had been enjoying a bath in the Mediterranean Sea. In the additional examinations, slight abnormalities were detected only in the results of blood agglutination test. The patient was discharged from the hospital 7 days later in good condition.

  9. The Cardiovascular and Neurotoxic Effects of the Venoms of Six Bony and Cartilaginous Fish Species

    PubMed Central

    Han, Han; Baumann, Kate; Casewell, Nicholas R.; Ali, Syed A.; Dobson, James; Koludarov, Ivan; Debono, Jordan; Cutmore, Scott C.; Rajapakse, Niwanthi W.; Jackson, Timothy N. W.; Jones, Rob; Hodgson, Wayne C.; Fry, Bryan G.; Kuruppu, Sanjaya

    2017-01-01

    Fish venoms are often poorly studied, in part due to the difficulty in obtaining, extracting, and storing them. In this study, we characterize the cardiovascular and neurotoxic effects of the venoms from the following six species of fish: the cartilaginous stingrays Neotrygon kuhlii and Himantura toshi, and the bony fish Platycephalus fucus, Girella tricuspidata, Mugil cephalus, and Dentex tumifrons. All venoms (10–100 µg/kg, i.v.), except G. tricuspidata and P. fuscus, induced a biphasic response on mean arterial pressure (MAP) in the anesthetised rat. P. fucus venom exhibited a hypotensive response, while venom from G. tricuspidata displayed a single depressor response. All venoms induced cardiovascular collapse at 200 µg/kg, i.v. The in vitro neurotoxic effects of venom were examined using the chick biventer cervicis nerve-muscle (CBCNM) preparation. N. kuhlii, H. toshi, and P. fucus venoms caused concentration-dependent inhibition of indirect twitches in the CBCNM preparation. These three venoms also inhibited responses to exogenous acetylcholine (ACh) and carbachol (CCh), but not potassium chloride (KCl), indicating a post-synaptic mode of action. Venom from G. tricuspidata, M. cephalus, and D. tumifrons had no significant effect on indirect twitches or agonist responses in the CBCNM. Our results demonstrate that envenoming by these species of fish may result in moderate cardiovascular and/or neurotoxic effects. Future studies aimed at identifying the molecules responsible for these effects could uncover potentially novel lead compounds for future pharmaceuticals, in addition to generating new knowledge about the evolutionary relationships between venomous animals. PMID:28212333

  10. Intraspecific variation of venom injected by fish-hunting Conus snails.

    PubMed

    Jakubowski, Jennifer A; Kelley, Wayne P; Sweedler, Jonathan V; Gilly, William F; Schulz, Joseph R

    2005-08-01

    Venom peptides from two species of fish-hunting cone snails (Conus striatus and Conus catus) were characterized using microbore liquid chromatography coupled with matrix-assisted laser desorption/ionization-time of flight-mass spectrometry and electrospray ionization-ion trap-mass spectrometry. Both crude venom isolated from the venom duct and injected venom obtained by milking were studied. Based on analysis of injected venom samples from individual snails, significant intraspecific variation (i.e. between individuals) in the peptide complement is observed. The mixture of peptides in injected venom is simpler than that in the crude duct venom from the same snail, and the composition of crude venom is more consistent from snail to snail. While there is animal-to-animal variation in the peptides present in the injected venom, the composition of any individual's injected venom remains relatively constant over time in captivity. Most of the Conus striatus individuals tested injected predominantly a combination of two neuroexcitatory peptides (s4a and s4b), while a few individuals had unique injected-venom profiles consisting of a combination of peptides, including several previously characterized from the venom duct of this species. Seven novel peptides were also putatively identified based on matches of their empirically derived masses to those predicted by published cDNA sequences. Profiling injected venom of Conus catus individuals using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry demonstrates that intraspecific variation in the mixture of peptides extends to other species of piscivorous cone snails. The results of this study imply that novel regulatory mechanisms exist to select specific venom peptides for injection into prey.

  11. Behavior, Ecology and Toxicity of Venomous Marine Fishes.

    DTIC Science & Technology

    1976-09-30

    man, and more definitive investigations on the usual ultracellular structure of their venom glands. The present report treats of our most recent study on the venom gland of the stingray Dasytis sabina. (Author)

  12. Purified Lesser weever fish venom (Trachinus vipera) induces eryptosis, apoptosis and cell cycle arrest

    PubMed Central

    Fezai, Myriam; Slaymi, Chaker; Ben-Attia, Mossadok; Lang, Florian; Jemaà, Mohamed

    2016-01-01

    Accidents caused by the sting of Trachinus vipera (known as Lesser weever fish) are relatively common in shallow waters of the Mediterranean. Symptoms after the sting vary from severe pain to edema or even tissue necrosis in some cases. Here we show that purified Lesser weever fish venom induces eryptosis, the suicidal erythrocyte death, and apoptosis of human colon carcinoma cells. The venom leads to erythrocyte shrinkage, phosphatidylserine translocation and increased intracellular Ca2+, events typical for eryptosis. According to mitochondrial staining cancer cells dyed after the activation of the intrinsic apoptotic pathway. Trachinus vipera venom further causes cell cycle arrest. PMID:27995979

  13. Analysis of the intersexual variation in Thalassophryne maculosa fish venoms.

    PubMed

    Lopes-Ferreira, Mônica; Sosa-Rosales, Ines; Bruni, Fernanda M; Ramos, Anderson D; Vieira Portaro, Fernanda Calheta; Conceição, Katia; Lima, Carla

    2016-06-01

    Gender related variation in the molecular composition of venoms and secretions have been described for some animal species, and there are some evidences that the difference in the toxin (s) profile among males and females may be related to different physiopathological effects caused by the envenomation by either gender. In order to investigate whether this same phenomenon occurs to the toadfish Thalassophryne maculosa, we have compared some biological and biochemical properties of female and male venoms. Twenty females and males were collected in deep waters of the La Restinga lagoon (Venezuela) and, after protein concentration assessed, the induction of toxic activities in mice and the biochemical properties were analyzed. Protein content is higher in males than in females, which may be associated to a higher size and weight of the male body. In vivo studies showed that mice injected with male venoms presented higher nociception when compared to those injected with female venoms, and both venoms induced migration of macrophages into the paw of mice. On the other hand, mice injected with female venoms had more paw edema and extravasation of Evans blue in peritoneal cavity than mice injected with male venoms. We observed that the female venoms had more capacity for necrosis induction when compared with male venoms. The female samples present a higher proteolytic activity then the male venom when gelatin, casein and FRETs were used as substrates. Evaluation of the venoms of females and males by SDS-PAGE and chromatographic profile showed that, at least three components (present in two peaks) are only present in males. Although the severity of the lesion, characterized by necrosis development, is related with the poisoning by female specimens, the presence of exclusive toxins in the male venoms could be associated with the largest capacity of nociception induction by this sample. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. The Evolution of Fangs, Venom, and Mimicry Systems in Blenny Fishes.

    PubMed

    Casewell, Nicholas R; Visser, Jeroen C; Baumann, Kate; Dobson, James; Han, Han; Kuruppu, Sanjaya; Morgan, Michael; Romilio, Anthony; Weisbecker, Vera; Ali, Syed A; Debono, Jordan; Koludarov, Ivan; Que, Ivo; Bird, Gregory C; Cooke, Gavan M; Nouwens, Amanda; Hodgson, Wayne C; Wagstaff, Simon C; Cheney, Karen L; Vetter, Irina; van der Weerd, Louise; Richardson, Michael K; Fry, Bryan G

    2017-04-24

    Venom systems have evolved on multiple occasions across the animal kingdom, and they can act as key adaptations to protect animals from predators [1]. Consequently, venomous animals serve as models for a rich source of mimicry types, as non-venomous species benefit from reductions in predation risk by mimicking the coloration, body shape, and/or movement of toxic counterparts [2-5]. The frequent evolution of such deceitful imitations provides notable examples of phenotypic convergence and are often invoked as classic exemplars of evolution by natural selection. Here, we investigate the evolution of fangs, venom, and mimetic relationships in reef fishes from the tribe Nemophini (fangblennies). Comparative morphological analyses reveal that enlarged canine teeth (fangs) originated at the base of the Nemophini radiation and have enabled a micropredatory feeding strategy in non-venomous Plagiotremus spp. Subsequently, the evolution of deep anterior grooves and their coupling to venom secretory tissue provide Meiacanthus spp. with toxic venom that they effectively employ for defense. We find that fangblenny venom contains a number of toxic components that have been independently recruited into other animal venoms, some of which cause toxicity via interactions with opioid receptors, and result in a multifunctional biochemical phenotype that exerts potent hypotensive effects. The evolution of fangblenny venom has seemingly led to phenotypic convergence via the formation of a diverse array of mimetic relationships that provide protective (Batesian mimicry) and predatory (aggressive mimicry) benefits to other fishes [2, 6]. Our results further our understanding of how novel morphological and biochemical adaptations stimulate ecological interactions in the natural world. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. The first report on coagulation and phospholipase A2 activities of Persian Gulf lionfish, Pterois russelli, an Iranian venomous fish.

    PubMed

    Memar, Bahareh; Jamili, Shahla; Shahbazzadeh, Delavar; Bagheri, Kamran Pooshang

    2016-04-01

    Pterois russelli is a venomous fish belonging to scorpionidae family. Regarding to high significance value for tracing potential therapeutic molecules and special agents from venomous marine creatures, the present study was aimed to characterization of the Persian Gulf lionfish venom. Proteolytic, phospholipase, hemolytic, coagulation, edematogenic and dermonecrotic activities were determined for extracted venom. The LD50 of P. russelli venom was determined by intravenous injection in white Balb/c mice. Phospholipase A2 activity was recorded at 20 μg of total venom. Coagulation activity on human plasma was shown by Prothrombin Time (PT) and activated Partial Thromboplastin Time (APTT) assays and coagulation visualized after 7 and 14 s respectively for 60 μg of crude venom. LD50 was calculated as 10.5 mg/kg. SDS-PAGE revealed the presence of major and minor protein bands between 6 and 205 kDa. Different amounts of crude venom ranged from 1.87 to 30 μg showed proteolytic activity on casein. The highest edematic activity was detected at 20 μg. Our findings showed that the edematic activity was dose dependent and persisted for 48 h after injection. The crude venom did not induce dermonecrotic activity on rabbit skin and showed no hemolytic activity on human, mouse and rabbit erythrocytes. This is the first report for phospholipase A2 and coagulation activity in venomous fish and venomous marine animals respectively. Proteolytic activity of P. russelli venom is in accordance with the other genara of scorpionidae family. According to venom activity on intrinsic and extrinsic coagulation pathways, lionfish venom would be contained an interesting pharmaceutical agent. This study is pending to further characterization of phospholipase A2, coagulation, and protease activities and also in vivo activity on animal model of surface and internal bleeding. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Isolation and characterization of dracotoxin from the venom of the greater weever fish Trachinus draco.

    PubMed

    Chhatwal, I; Dreyer, F

    1992-01-01

    Dracotoxin, a protein possessing toxic, membrane depolarizing and hemolytic activities, was isolated from the crude venom of the greater weever fish Trachinus draco. The purification involved ammonium sulfate precipitation of crude venom followed by gel filtration on a high performance liquid chromatograph column. About 300 micrograms of dracotoxin was obtained from 18 mg of crude venom proteins extracted from one average size fish. Dracotoxin consists of a single polypeptide of about 105,000 mol. wt. It hemolyzed rabbit erythrocytes with an EC50 of 3 ng/ml. Rabbit erythrocytes possessed binding sites for dracotoxin on their surface. Preincubation of dracotoxin with rabbit ghosts increased its EC50 value for rabbit erthrocytes from 3 to 25 ng/ml. Incubation of dracotoxin with enriched glycophorin fraction from rabbit erythrocytes also led to an increase in the EC50 to 70 ng/ml. The high specificity of dracotoxin for rabbit erythrocytes resembles that of staphylococcal alpha-toxin. Dracotoxin, however, caused hemolysis even at 4 degrees C and did not interact with cholesterol indicating substantial differences between the two hemolysins. Dracotoxin represents a major toxic component of T. draco venom.

  17. Maintaining Coral Snakes (Micrurus nigrocinctus, Serpentes: Elapidae) for venom production on an alternative fish-based diet.

    PubMed

    Chacón, Danilo; Rodríguez, Santos; Arias, Jazmín; Solano, Gabriela; Bonilla, Fabián; Gómez, Aarón

    2012-09-01

    American Elapid snakes (Coral Snakes) comprise the genera Leptomicrurus, Micruroides and Micrurus, which form a vast taxonomic assembly of 330 species distributed from the South of United States to the southern region of South America. In order to obtain venom for animal immunizations aimed at antivenom production, Coral Snakes must be kept in captivity and submitted periodically to venom extraction procedures. Thus, to maintain a snake colony in good health for this purpose, a complete alternative diet utilizing an easily obtained prey animal is desirable. The development of a diet based on fish is compared to the wild diet based on colubrid snakes, and assessed in terms of gain in body weight rate (g/week), longevity (weeks), venom yield (mg/individual), venom median lethal dose (LD₅₀) and venom chromatographic profiles. The animals fed with the fish-based diet gained more weight, lived longer, and produced similar amount of venom whose biological and biochemical characteristics were similar to those of venom collected from specimens fed with the wild diet. This fish-based diet appears to be suitable (and preferable to the wild diet) to supply the nutritional requirements of a Micrurus nigrocinctus snake collection for the production of antivenom. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Insights into the origins of fish hunting in venomous cone snails from studies of Conus tessulatus

    PubMed Central

    Aman, Joseph W.; Imperial, Julita S.; Ueberheide, Beatrix; Zhang, Min-Min; Aguilar, Manuel; Taylor, Dylan; Watkins, Maren; Yoshikami, Doju; Showers-Corneli, Patrice; Safavi-Hemami, Helena; Biggs, Jason; Teichert, Russell W.; Olivera, Baldomero M.

    2015-01-01

    Prey shifts in carnivorous predators are events that can initiate the accelerated generation of new biodiversity. However, it is seldom possible to reconstruct how the change in prey preference occurred. Here we describe an evolutionary “smoking gun” that illuminates the transition from worm hunting to fish hunting among marine cone snails, resulting in the adaptive radiation of fish-hunting lineages comprising ∼100 piscivorous Conus species. This smoking gun is δ-conotoxin TsVIA, a peptide from the venom of Conus tessulatus that delays inactivation of vertebrate voltage-gated sodium channels. C. tessulatus is a species in a worm-hunting clade, which is phylogenetically closely related to the fish-hunting cone snail specialists. The discovery of a δ-conotoxin that potently acts on vertebrate sodium channels in the venom of a worm-hunting cone snail suggests that a closely related ancestral toxin enabled the transition from worm hunting to fish hunting, as δ-conotoxins are highly conserved among fish hunters and critical to their mechanism of prey capture; this peptide, δ-conotoxin TsVIA, has striking sequence similarity to these δ-conotoxins from piscivorous cone snail venoms. Calcium-imaging studies on dissociated dorsal root ganglion (DRG) neurons revealed the peptide’s putative molecular target (voltage-gated sodium channels) and mechanism of action (inhibition of channel inactivation). The results were confirmed by electrophysiology. This work demonstrates how elucidating the specific interactions between toxins and receptors from phylogenetically well-defined lineages can uncover molecular mechanisms that underlie significant evolutionary transitions. PMID:25848010

  19. Insights into the origins of fish hunting in venomous cone snails from studies of Conus tessulatus.

    PubMed

    Aman, Joseph W; Imperial, Julita S; Ueberheide, Beatrix; Zhang, Min-Min; Aguilar, Manuel; Taylor, Dylan; Watkins, Maren; Yoshikami, Doju; Showers-Corneli, Patrice; Safavi-Hemami, Helena; Biggs, Jason; Teichert, Russell W; Olivera, Baldomero M

    2015-04-21

    Prey shifts in carnivorous predators are events that can initiate the accelerated generation of new biodiversity. However, it is seldom possible to reconstruct how the change in prey preference occurred. Here we describe an evolutionary "smoking gun" that illuminates the transition from worm hunting to fish hunting among marine cone snails, resulting in the adaptive radiation of fish-hunting lineages comprising ∼100 piscivorous Conus species. This smoking gun is δ-conotoxin TsVIA, a peptide from the venom of Conus tessulatus that delays inactivation of vertebrate voltage-gated sodium channels. C. tessulatus is a species in a worm-hunting clade, which is phylogenetically closely related to the fish-hunting cone snail specialists. The discovery of a δ-conotoxin that potently acts on vertebrate sodium channels in the venom of a worm-hunting cone snail suggests that a closely related ancestral toxin enabled the transition from worm hunting to fish hunting, as δ-conotoxins are highly conserved among fish hunters and critical to their mechanism of prey capture; this peptide, δ-conotoxin TsVIA, has striking sequence similarity to these δ-conotoxins from piscivorous cone snail venoms. Calcium-imaging studies on dissociated dorsal root ganglion (DRG) neurons revealed the peptide's putative molecular target (voltage-gated sodium channels) and mechanism of action (inhibition of channel inactivation). The results were confirmed by electrophysiology. This work demonstrates how elucidating the specific interactions between toxins and receptors from phylogenetically well-defined lineages can uncover molecular mechanisms that underlie significant evolutionary transitions.

  20. A comparative study of the molecular composition and electrophysiological activity of the venoms from two fishing spiders Dolomedes mizhoanus and Dolomedes sulfurous.

    PubMed

    Li, Jiayan; Li, Dan; Zhang, Fan; Wang, Hengyun; Yu, Hai; Liu, Zhonghua; Liang, Songping

    2014-06-01

    Dolomedes mizhoanus and Dolomedes sulfurous are two venomous spiders found in the same area in southern China and are characterized by living in water plants and feeding on fish. In this study, the chemical compositions and activities of these venoms were compared. Both venoms contain hundreds of peptides as shown by off-line RP-HPLC/MALDI-TOF-MS analysis, but have a different peptide distribution, with D. mizhoanus venom containing fewer high molecular mass (7000-9000 Da) peptides (3%) than D. sulfurous venom (25.6%). Patch-clamp analyses showed that both venoms inhibited voltage-activated Na(+), K(+) and Ca(2+) channels in rat DRG neurons, however, differences in their inhibitory effects were observed. In general, D. mizhoanus venom had lower inhibitory activity than D. sulfurous venom and both venoms had a different inhibitory spectrum against these ion channels, showing that both venoms are useful for identifying antagonists to them. In addition, intrathoracic injection of both venoms caused severe neurotoxic effects in zebrafish and death at higher concentrations, respectively. Considering that both spiders belong to the same genus, live in the same area and have similar habits, elucidation of the differences between the peptide toxins from both venoms would provide new molecular insights into the evolution of spider peptides.

  1. A Comparative Analysis of the Venom Gland Transcriptomes of the Fishing Spiders Dolomedes mizhoanus and Dolomedes sulfurous

    PubMed Central

    Xu, Xunxun; Wang, Hengyun; Zhang, Fang; Hu, Zhaotun; Liang, Songping; Liu, Zhonghua

    2015-01-01

    Dolomedes sulfurous and Dolomedes mizhoanus are predaceous arthropods catching and feeding on small fish. They live in the same area and have similar habits. Their venoms exhibit some similarities and differences in biochemical and electrophysiological properties. In the present work, we first performed a transcriptomic analysis by constructing the venom gland cDNA library of D. sulfurous and 127 novel putative toxin sequences were consequently identified, which were classified into eight families. This venom gland transcriptome was then compared with that of D. mizhoanus, which revealed that the putative toxins from both spider venoms might have originated from the same gene ancestors although novel toxins were evolved independently in the two spiders. The putative toxins from both spiders contain 6–12 cysteine residues forming seven cysteine patterns. As revealed by blast search, the two venoms are rich in neurotoxins targeting ion channels with pharmacological and therapeutic significance. This study provides insight into the venoms of two closely related species of spider, which will be of use for future investigations into the structure and function of their toxins. PMID:26445494

  2. A Comparative Analysis of the Venom Gland Transcriptomes of the Fishing Spiders Dolomedes mizhoanus and Dolomedes sulfurous.

    PubMed

    Xu, Xunxun; Wang, Hengyun; Zhang, Fang; Hu, Zhaotun; Liang, Songping; Liu, Zhonghua

    2015-01-01

    Dolomedes sulfurous and Dolomedes mizhoanus are predaceous arthropods catching and feeding on small fish. They live in the same area and have similar habits. Their venoms exhibit some similarities and differences in biochemical and electrophysiological properties. In the present work, we first performed a transcriptomic analysis by constructing the venom gland cDNA library of D. sulfurous and 127 novel putative toxin sequences were consequently identified, which were classified into eight families. This venom gland transcriptome was then compared with that of D. mizhoanus, which revealed that the putative toxins from both spider venoms might have originated from the same gene ancestors although novel toxins were evolved independently in the two spiders. The putative toxins from both spiders contain 6-12 cysteine residues forming seven cysteine patterns. As revealed by blast search, the two venoms are rich in neurotoxins targeting ion channels with pharmacological and therapeutic significance. This study provides insight into the venoms of two closely related species of spider, which will be of use for future investigations into the structure and function of their toxins.

  3. Large-scale discovery of conopeptides and conoproteins in the injectable venom of a fish-hunting cone snail using a combined proteomic and transcriptomic approach.

    PubMed

    Violette, Aude; Biass, Daniel; Dutertre, Sébastien; Koua, Dominique; Piquemal, David; Pierrat, Fabien; Stöcklin, Reto; Favreau, Philippe

    2012-09-18

    Predatory marine snails of the genus Conus use venom containing a complex mixture of bioactive peptides to subdue their prey. Here we report on a comprehensive analysis of the protein content of injectable venom from Conus consors, an indo-pacific fish-hunting cone snail. By matching MS/MS data against an extensive set of venom gland transcriptomic mRNA sequences, we identified 105 components out of ~400 molecular masses detected in the venom. Among them, we described new conotoxins belonging to the A, M- and O1-superfamilies as well as a novel superfamily of disulphide free conopeptides. A high proportion of the deduced sequences (36%) corresponded to propeptide regions of the A- and M-superfamilies, raising the question of their putative role in injectable venom. Enzymatic digestion of higher molecular mass components allowed the identification of new conkunitzins (~7 kDa) and two proteins in the 25 and 50 kDa molecular mass ranges respectively characterised as actinoporin-like and hyaluronidase-like protein. These results provide the most exhaustive and accurate proteomic overview of an injectable cone snail venom to date, and delineate the major protein families present in the delivered venom. This study demonstrates the feasibility of this analytical approach and paves the way for transcriptomics-assisted strategies in drug discovery.

  4. Proteomic analysis of the venom from the fish eating coral snake Micrurus surinamensis: novel toxins, their function and phylogeny.

    PubMed

    Olamendi-Portugal, Timoteo; Batista, Cesar V F; Restano-Cassulini, Rita; Pando, Victoria; Villa-Hernandez, Oscar; Zavaleta-Martínez-Vargas, Alfonso; Salas-Arruz, Maria C; Rodríguez de la Vega, Ricardo C; Becerril, Baltazar; Possani, Lourival D

    2008-05-01

    The protein composition of the soluble venom from the South American fish-eating coral snake Micrurus surinamensis surinamensis, here abbreviated M. surinamensis, was separated by RP-HPLC and 2-DE, and their components were analyzed by automatic Edman degradation, MALDI-TOF and ESI-MS/MS. Approximately 100 different molecules were identified. Sixty-two components possess molecular masses between 6 and 8 kDa, are basically charged molecules, among which are cytotoxins and neurotoxins lethal to fish (Brachidanios rerio). Six new toxins (abbreviated Ms1-Ms5 and Ms11) were fully sequenced. Amino acid sequences similar to the enzymes phospholipase A2 and amino acid oxidase were identified. Over 20 additional peptides were identified by sequencing minor components of the HPLC separation and from 2-DE gels. A functional assessment of the physiological activity of the six toxins was also performed by patch clamp using muscular nicotinic acetylcholine receptor assays. Variable degrees of blockade were observed, most of them reversible. The structural and functional data obtained were used for phylogenetic analysis, providing information on some evolutionary aspects of the venom components of this snake. This contribution increases by a factor of two the total number of alpha-neurotoxins sequenced from the Micrurus genus in currently available literature.

  5. The Cardiovascular and Neurotoxic Effects of the  Venoms of Six Bony and Cartilaginous Fish Species.

    PubMed

    Han, Han; Baumann, Kate; Casewell, Nicholas R; Ali, Syed A; Dobson, James; Koludarov, Ivan; Debono, Jordan; Cutmore, Scott C; Rajapakse, Niwanthi W; Jackson, Timothy N W; Jones, Rob; Hodgson, Wayne C; Fry, Bryan G; Kuruppu, Sanjaya

    2017-02-16

    Fish venoms are often poorly studied, in part due to the difficulty in obtaining, extracting, and storing them. In this study, we characterize the cardiovascular and neurotoxic effects of the venoms from the following six species of fish: the cartilaginous stingrays Neotrygon kuhlii and Himantura toshi, and the bony fish Platycephalus fucus, Girella tricuspidata, Mugil cephalus, and Dentex tumifrons. All venoms (10-100 μg/kg, i.v.), except G. tricuspidata and P. fuscus, induced a biphasic response on mean arterial pressure (MAP) in the anesthetised rat. P. fucus venom exhibited a hypotensive response, while venom from G. tricuspidata displayed a single depressor response. All venoms induced cardiovascular collapse at 200 μg/kg, i.v. The in vitro neurotoxic effects of venom were examined using the chick biventer cervicis nerve-muscle (CBCNM) preparation. N. kuhlii, H. toshi, and P. fucus venoms caused concentration-dependent inhibition of indirect twitches in the CBCNM preparation. These three venoms also inhibited responses to exogenous acetylcholine (ACh) and carbachol (CCh), but not potassium chloride (KCl), indicating a post-synaptic mode of action. Venom from G. tricuspidata, M. cephalus, and D. tumifrons had no significant effect on indirect twitches or agonist responses in the CBCNM. Our results demonstrate that envenoming by these species of fish may result in moderate cardiovascular and/or neurotoxic effects. Future studies aimed at identifying the molecules responsible for these effects could uncover potentially novel lead compounds for future pharmaceuticals, in addition to generating new knowledge about the evolutionary relationships between venomous animals.

  6. Evolution: Fangtastic Venoms Underpin Parasitic Mimicry.

    PubMed

    Taylor, Martin I

    2017-04-24

    Venomous teeth are rare in fishes, which typically utilise spines for defence. A new study reveals the evolutionary origins of fangs and venom in the Nemophini blennies and shows that, in contrast to snakes and lizards, the fangs pre-date the venom. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  7. Tropical marine neurotoxins: venoms to drugs.

    PubMed

    Watters, Michael R

    2005-09-01

    Neurotoxic venoms are common among tropical marine creatures, which have specialized apparatuses for delivery of the venoms. These include jellyfish and anemones, venomous cone snails, venomous fish, stingrays, sea snakes, and venomous octopuses. Numerous toxic neuropeptides are found within these venoms, and some can discriminate between closely related intracellular targets, a characteristic that makes them useful to define cation channels and attractive for drug development. A synthetic derivative of an omega-conotoxin is now available, representing a new class of analgesics. In general, toxic marine venoms contain proteins that are heat labile, providing opportunity for therapeutic intervention following envenomation, while ingestible seafood toxins are thermostable toxins. Ingestible toxins found in the tropics include those associated with reef fish, pufferfish, and some shellfish, which serve as food-chain vectors for toxins produced by marine microorganisms.

  8. Neutralizing antibodies obtained in a persistent immune response are effective against deleterious effects induced by the Thalassophryne nattereri fish venom.

    PubMed

    Piran-Soares, Ana Amélia; Komegae, Evilin Naname; Souza, Valdênia Maria Oliveira; Fonseca, Luiz Alberto; Lima, Carla; Lopes-Ferreira, Mônica

    2007-06-01

    Thalassophryne nattereri envenoming represents a great cost to North and Northeast Brazilian communities in terms of public healths, leisure and tourism. Victims rapidally develop symptoms as pain, local swelling, erythema followed by intense necrosis that persist for long days. The aim of this work was tested the immune competence of neutralizing antibodies in pre-immunized mice against principal toxic activities induced by venom. During the primary antibody response in mice, an elevation of IgG antibody levels was only observed on day 28. After boosting, high antibody levels were detected between days 49 and 70, with a 12-fold increase in IgG level over control values at day 49. We confirmed the in vitro neutralizing capacity of T. nattereri anti-venom against toxic effects and thereafter we show that neutralizing antibodies obtained in a persistent immune response are more effective, inclusive against edematous reaction. After boosting during the secondary response mice with high antibody levels do not present any alterations in venule or arteriole after topical application of venom on cremaster muscle. In addition, CK activity diminished in these mice with high neutralizing antibody levels corroborating the attenuation of the myonecrotic effect by venom. In addition, we determined the presence of high IgG antibodies levels in patients 6 months after injury by T. nattereri. In conclusion, the presence of neutralizing antibodies against to T. nattereri venom in the serum of pre-immunized mice could change the outcome of lesion at site of posterior envenoming. Antigen-specific antibodies of high affinity in consequence to specific immune response, dependent of T lymphocyte activation, could minimize the symptoms of intense and immediate inflammatory reaction caused by T. nattereri venom. These finding prompt us to the possibility of development of immune therapeutic strategies using specific anti-venom as an efficient intervention for protecting human victims.

  9. Ichthyotoxicity caused by marine cone snail venoms?

    PubMed

    Mebs, Dietrich; Kauferstein, Silke

    2005-09-01

    Ten venoms from marine cone snails were tested for ichthyotoxic effects on zebra fish (Brachydanio rerio) when added to the water. Only two venoms, from Conus capitaneus and Conus episcopatus, produced lethal effects at high concentrations (50-300 microg/ml) within 20-90 min. No sedative or hypnotic symptoms were observed. The experiments confirm that Conus venoms exert a quick and prompt activity only by parenteral injection into the prey as it is performed by the snail.

  10. Novel venom gene discovery in the platypus

    PubMed Central

    2010-01-01

    Background To date, few peptides in the complex mixture of platypus venom have been identified and sequenced, in part due to the limited amounts of platypus venom available to study. We have constructed and sequenced a cDNA library from an active platypus venom gland to identify the remaining components. Results We identified 83 novel putative platypus venom genes from 13 toxin families, which are homologous to known toxins from a wide range of vertebrates (fish, reptiles, insectivores) and invertebrates (spiders, sea anemones, starfish). A number of these are expressed in tissues other than the venom gland, and at least three of these families (those with homology to toxins from distant invertebrates) may play non-toxin roles. Thus, further functional testing is required to confirm venom activity. However, the presence of similar putative toxins in such widely divergent species provides further evidence for the hypothesis that there are certain protein families that are selected preferentially during evolution to become venom peptides. We have also used homology with known proteins to speculate on the contributions of each venom component to the symptoms of platypus envenomation. Conclusions This study represents a step towards fully characterizing the first mammal venom transcriptome. We have found similarities between putative platypus toxins and those of a number of unrelated species, providing insight into the evolution of mammalian venom. PMID:20920228

  11. Diversity, phylogenetic distribution, and origins of venomous catfishes

    PubMed Central

    2009-01-01

    Background The study of venomous fishes is in a state of relative infancy when compared to that of other groups of venomous organisms. Catfishes (Order Siluriformes) are a diverse group of bony fishes that have long been known to include venomous taxa, but the extent and phylogenetic distribution of this venomous species diversity has never been documented, while the nature of the venoms themselves also remains poorly understood. In this study, I used histological preparations from over 100 catfish genera, basic biochemical and toxicological analyses of fin spine extracts from several species, and previous systematic studies of catfishes to examine the distribution of venom glands in this group. These results also offer preliminary insights into the evolutionary history of venom glands in the Siluriformes. Results Histological examinations of 158 catfish species indicate that approximately 1250-1625+ catfish species should be presumed to be venomous, when viewed in conjunction with several hypotheses of siluriform phylogeny. Maximum parsimony character optimization analyses indicate two to three independent derivations of venom glands within the Siluriformes. A number of putative toxic peptides were identified in the venoms of catfish species from many of the families determined to contain venomous representatives. These peptides elicit a wide array of physiological effects in other fishes, though any one species examined produced no more than three distinct putative toxins in its venom. The molecular weights and effects produced by these putative toxic peptides show strong similarities to previously characterized toxins found in catfish epidermal secretions. Conclusion Venom glands have evolved multiple times in catfishes (Order Siluriformes), and venomous catfishes may outnumber the combined diversity of all other venomous vertebrates. The toxic peptides found in catfish venoms may be derived from epidermal secretions that have been demonstrated to accelerate the

  12. Diversity, phylogenetic distribution, and origins of venomous catfishes.

    PubMed

    Wright, Jeremy J

    2009-12-04

    The study of venomous fishes is in a state of relative infancy when compared to that of other groups of venomous organisms. Catfishes (Order Siluriformes) are a diverse group of bony fishes that have long been known to include venomous taxa, but the extent and phylogenetic distribution of this venomous species diversity has never been documented, while the nature of the venoms themselves also remains poorly understood. In this study, I used histological preparations from over 100 catfish genera, basic biochemical and toxicological analyses of fin spine extracts from several species, and previous systematic studies of catfishes to examine the distribution of venom glands in this group. These results also offer preliminary insights into the evolutionary history of venom glands in the Siluriformes. Histological examinations of 158 catfish species indicate that approximately 1250-1625+ catfish species should be presumed to be venomous, when viewed in conjunction with several hypotheses of siluriform phylogeny. Maximum parsimony character optimization analyses indicate two to three independent derivations of venom glands within the Siluriformes. A number of putative toxic peptides were identified in the venoms of catfish species from many of the families determined to contain venomous representatives. These peptides elicit a wide array of physiological effects in other fishes, though any one species examined produced no more than three distinct putative toxins in its venom. The molecular weights and effects produced by these putative toxic peptides show strong similarities to previously characterized toxins found in catfish epidermal secretions. Venom glands have evolved multiple times in catfishes (Order Siluriformes), and venomous catfishes may outnumber the combined diversity of all other venomous vertebrates. The toxic peptides found in catfish venoms may be derived from epidermal secretions that have been demonstrated to accelerate the healing of wounds, rather

  13. Snake oil and venoms for medical research

    NASA Astrophysics Data System (ADS)

    Wolpert, H. D.

    2011-04-01

    Some think that using derivatives of snake venom for medical purposes is the modern version of snake oil but they are seriously misjudging the research potentials of some of these toxins in medicines of the 2000's. Medical trials, using some of the compounds has proven their usefulness. Several venoms have shown the possibilities that could lead to anticoagulants, helpful in heart disease. The blood clotting protein from the taipan snake has been shown to rapidly stop excessive bleeding. The venom from the copperhead may hold an answer to breast cancer. The Malaysian pit viper shows promise in breaking blood clots. Cobra venom may hold keys to finding cures for Parkinson's disease and Alzheimer's. Rattlesnake proteins from certain species have produced blood pressure medicines. Besides snake venoms, venom from the South American dart frog, mollusks (i.e. Cone Shell Snail), lizards (i.e. Gila Monster & Komodo Dragon), some species of spiders and tarantulas, Cephalopods, mammals (i.e. Platypus & Shrews), fish (i.e. sting rays, stone fish, puffer fish, blue bottle fish & box jelly fish), intertidal marine animals (echinoderms)(i.e. Crown of Thorn Star Fish & Flower Urchin) and the Honeybee are being investigated for potential medical benefits.

  14. Multiple functional therapeutic effects of TnP: A small stable synthetic peptide derived from fish venom in a mouse model of multiple sclerosis

    PubMed Central

    Komegae, Evilin Naname; Souza, Tais Aparecida Matozo; Grund, Lidiane Zito; Lima, Carla

    2017-01-01

    The pathological condition of multiple sclerosis (MS) relies on innate and adaptive immunity. New types of agents that beneficially modify the course of MS, stopping the progression and repairing the damage appear promising. Here, we studied TnP, a small stable synthetic peptide derived from fish venom in the control of inflammation and demyelination in experimental autoimmune encephalomyelitis as prophylactic treatment. TnP decreased the number of the perivascular infiltrates in spinal cord, and the activity of MMP-9 by F4/80+ macrophages were decreased after different regimen treatments. TnP reduces in the central nervous system the infiltration of IFN-γ-producing Th1 and IL-17A-producing Th17 cells. Also, treatment with therapeutic TnP promotes the emergence of functional Treg in the central nervous system entirely dependent on IL-10. Therapeutic TnP treatment accelerates the remyelination process in a cuprizone model of demyelination. These findings support the beneficial effects of TnP and provides a new therapeutic opportunity for the treatment of MS. PMID:28235052

  15. Proteomic interrogation of venom delivery in marine cone snails: novel insights into the role of the venom bulb.

    PubMed

    Safavi-Hemami, Helena; Young, Neil D; Williamson, Nicholas A; Purcell, Anthony W

    2010-11-05

    Cone snails of the genus Conus are predatory marine gastropods mainly found in the shallow waters of the tropics and warm temperate seas. To prey on other marine organisms including fish, cone snails have evolved complex venoms synthesized and delivered by a highly sophisticated venom apparatus. Upon prey discovery, the venom is perfused through a harpoon-like radula tooth and rapidly injected into the prey to cause paralysis. While the venom components of cone snails have been intensively characterized, the mechanism of venom translocation and loading prior to and during injection remains elusive. The involvement of the venom bulb, a muscular dilation of the venom gland has been suggested, however evidence is sparse. Here, we use a combination of proteomics, molecular biology, and morphological examination to elucidate the potential role of the venom bulb in venom translocation and delivery. Analysis of the venom bulb proteome clearly demonstrated a function of this organ in muscular movement and, more interestingly, in burst muscle contraction. Morphological examination revealed high structural similarities to the mantle muscle of squids, animals known for their rapid escape response. We sequenced and further characterized arginine kinase, a key protein of rapid muscular movement in invertebrates and show high concentrations of this enzyme in the bulb when compared to the venom gland and the foot muscle. Proteins characteristic for venom biosynthesis were low in abundance. On the basis of our findings, we suggest that the bulb of cone snails is a highly specialized organ of venom translocation. Delivery of venom is driven by burst contractions of the bulb rapidly forcing the venom through the radula tooth into the prey.

  16. The effect of venom skin testing on venom RAST titers.

    PubMed

    Green, R L; Levine, M I

    1982-03-01

    Venom RAST titers were measured in 20 insect-sensitive patients before and two to three weeks after skin testing with insect venoms to determine whether venom testing might cause a rise in venom IgE titers. No significant rise in venom-specific RAST titers for honey bee, wasp and yellow jacket venoms was observed.

  17. Are ticks venomous animals?

    PubMed Central

    2014-01-01

    Introduction As an ecological adaptation venoms have evolved independently in several species of Metazoa. As haematophagous arthropods ticks are mainly considered as ectoparasites due to directly feeding on the skin of animal hosts. Ticks are of major importance since they serve as vectors for several diseases affecting humans and livestock animals. Ticks are rarely considered as venomous animals despite that tick saliva contains several protein families present in venomous taxa and that many Ixodida genera can induce paralysis and other types of toxicoses. Tick saliva was previously proposed as a special kind of venom since tick venom is used for blood feeding that counteracts host defense mechanisms. As a result, the present study provides evidence to reconsider the venomous properties of tick saliva. Results Based on our extensive literature mining and in silico research, we demonstrate that ticks share several similarities with other venomous taxa. Many tick salivary protein families and their previously described functions are homologous to proteins found in scorpion, spider, snake, platypus and bee venoms. This infers that there is a structural and functional convergence between several molecular components in tick saliva and the venoms from other recognized venomous taxa. We also highlight the fact that the immune response against tick saliva and venoms (from recognized venomous taxa) are both dominated by an allergic immunity background. Furthermore, by comparing the major molecular components of human saliva, as an example of a non-venomous animal, with that of ticks we find evidence that ticks resemble more venomous than non-venomous animals. Finally, we introduce our considerations regarding the evolution of venoms in Arachnida. Conclusions Taking into account the composition of tick saliva, the venomous functions that ticks have while interacting with their hosts, and the distinguishable differences between human (non-venomous) and tick salivary

  18. Venomous bites, stings, and poisoning.

    PubMed

    Warrell, David A

    2012-06-01

    This article discusses the epidemiology, prevention, clinical features, first aid and medical treatment of venomous bites by snakes, lizards, and spiders; stings by fish, jellyfish, echinoderms, and insects; and poisoning by fish and molluscs, in all parts of the world. Of these envenoming and poisonings, snake bite causes the greatest burden of human suffering, killing 46,000 people each year in India alone and more than 100,000 worldwide and resulting in physical handicap in many survivors. Specific antidotes (antivenoms/antivenins) are available to treat envenoming by many of these taxa but supply and distribution is inadequate in many tropical developing countries. Copyright © 2012. Published by Elsevier Inc.

  19. [Venomous spiders and their venoms].

    PubMed

    Schmidt, G

    1985-01-01

    The history of araneidism is long and confusing. The superstition seems to be inexterminatable that tropical mygalomorphs and mediterranean tarantulas are dangerous for humans. It can be looked up even in the most recent edition of the widespread clinical dictionary of Pschyrembel. In contrast to this certain ctenids, the most dangerous spiders up to now known, are mentioned not at all in medical publications. Exaggerated spider-fear is out of place because about 0.1% of all species are dangerous for man only and many of the venomous species live as hidden as they scarcely come in contact with humans.

  20. Recruitment of glycosyl hydrolase proteins in a cone snail venomous arsenal: further insights into biomolecular features of Conus venoms.

    PubMed

    Violette, Aude; Leonardi, Adrijana; Piquemal, David; Terrat, Yves; Biass, Daniel; Dutertre, Sébastien; Noguier, Florian; Ducancel, Frédéric; Stöcklin, Reto; Križaj, Igor; Favreau, Philippe

    2012-02-01

    Cone snail venoms are considered an untapped reservoir of extremely diverse peptides, named conopeptides, displaying a wide array of pharmacological activities. We report here for the first time, the presence of high molecular weight compounds that participate in the envenomation cocktail used by these marine snails. Using a combination of proteomic and transcriptomic approaches, we identified glycosyl hydrolase proteins, of the hyaluronidase type (Hyal), from the dissected and injectable venoms ("injectable venom" stands for the venom variety obtained by milking of the snails. This is in contrast to the "dissected venom", which was obtained from dissected snails by extraction of the venom glands) of a fish-hunting cone snail, Conus consors (Pionoconus clade). The major Hyal isoform, Conohyal-Cn1, is expressed as a mixture of numerous glycosylated proteins in the 50 kDa molecular mass range, as observed in 2D gel and mass spectrometry analyses. Further proteomic analysis and venom duct mRNA sequencing allowed full sequence determination. Additionally, unambiguous segment location of at least three glycosylation sites could be determined, with glycans corresponding to multiple hexose (Hex) and N-acetylhexosamine (HexNAc) moieties. With respect to other known Hyals, Conohyal-Cn1 clearly belongs to the hydrolase-type of Hyals, with strictly conserved consensus catalytic donor and positioning residues. Potent biological activity of the native Conohyals could be confirmed in degrading hyaluronic acid. A similar Hyal sequence was also found in the venom duct transcriptome of C. adamsonii (Textilia clade), implying a possible widespread recruitment of this enzyme family in fish-hunting cone snail venoms. These results provide the first detailed Hyal sequence characterized from a cone snail venom, and to a larger extent in the Mollusca phylum, thus extending our knowledge on this protein family and its evolutionary selection in marine snail venoms.

  1. Venomics: integrative venom proteomics and beyond.

    PubMed

    Calvete, Juan J

    2017-02-20

    Venoms are integrated phenotypes that evolved independently in, and are used for predatory and defensive purposes by, a wide phylogenetic range of organisms. The same principles that contribute to the evolutionary success of venoms, contribute to making the study of venoms of great interest in such diverse fields as evolutionary ecology and biotechnology. Evolution is profoundly contingent, and nature also reinvents itself continuosly. Changes in a complex phenotypic trait, such as venom, reflect the influences of prior evolutionary history, chance events, and selection. Reconstructing the natural history of venoms, particularly those of snakes, which will be dealt with in more detail in this review, requires the integration of different levels of knowledge into a meaningful and comprehensive evolutionary framework for separating stochastic changes from adaptive evolution. The application of omics technologies and other disciplines have contributed to a qualitative and quantitative advance in the road map towards this goal. In this review we will make a foray into the world of animal venoms, discuss synergies and complementarities of the different approaches used in their study, and identify current bottlenecks that prevent inferring the evolutionary mechanisms and ecological constraints that molded snake venoms to their present-day variability landscape.

  2. AN INVESTIGATION OF POISONOUS AND VENOMOUS FISHES AT COCOS, GALAPAGOS AND LA PLATA ISLANDS DURING 4 DECEMBER 1952 TO 28 JANUARY 1953

    DTIC Science & Technology

    Collections of fish were made at Cocos , Galapagos, and La Plata Islands to determine if species known to be poisonous in the Indo-Pacific and West...tropical water currents and the respective fish fauna. Large numbers of puffers were present at Chatham Bay, Cocos and at Tagus Cove, Isabela...Galapagos. Moray eels and red snappers were numerous at La Plata, and sharks were exceedingly abundant at Cocos . Representative collections of fish were taken

  3. Elucidation of the molecular envenomation strategy of the cone snail Conus geographus through transcriptome sequencing of its venom duct

    PubMed Central

    2012-01-01

    Background The fish-hunting cone snail, Conus geographus, is the deadliest snail on earth. In the absence of medical intervention, 70% of human stinging cases are fatal. Although, its venom is known to consist of a cocktail of small peptides targeting different ion-channels and receptors, the bulk of its venom constituents, their sites of manufacture, relative abundances and how they function collectively in envenomation has remained unknown. Results We have used transcriptome sequencing to systematically elucidate the contents the C. geographus venom duct, dividing it into four segments in order to investigate each segment’s mRNA contents. Three different types of calcium channel (each targeted by unrelated, entirely distinct venom peptides) and at least two different nicotinic receptors appear to be targeted by the venom. Moreover, the most highly expressed venom component is not paralytic, but causes sensory disorientation and is expressed in a different segment of the venom duct from venoms believed to cause sensory disruption. We have also identified several new toxins of interest for pharmaceutical and neuroscience research. Conclusions Conus geographus is believed to prey on fish hiding in reef crevices at night. Our data suggest that disorientation of prey is central to its envenomation strategy. Furthermore, venom expression profiles also suggest a sophisticated layering of venom-expression patterns within the venom duct, with disorientating and paralytic venoms expressed in different regions. Thus, our transcriptome analysis provides a new physiological framework for understanding the molecular envenomation strategy of this deadly snail. PMID:22742208

  4. Venomous mammals: a review.

    PubMed

    Ligabue-Braun, Rodrigo; Verli, Hugo; Carlini, Célia Regina

    2012-06-01

    The occurrence of venom in mammals has long been considered of minor importance, but recent fossil discoveries and advances in experimental techniques have cast new light into this subject. Mammalian venoms form a heterogeneous group having different compositions and modes of action and are present in three classes of mammals, Insectivora, Monotremata, and Chiroptera. A fourth order, Primates, is proposed to have venomous representatives. In this review we highlight recent advances in the field while summarizing biochemical characteristics of these secretions and their effects upon humans and other animals. Historical aspects of venom discovery and evolutionary hypothesis regarding their origin are also discussed.

  5. [Toxicology of Hymenoptera venoms].

    PubMed

    Ciszowski, Krzysztof; Mietka-Ciszowska, Aneta

    2012-01-01

    Hymenoptera venom is a secretion of special poison glands of insects. It serves both as a defensive substance against aggressors, as well as weapon used to paralyze the victim during gaining food. Chemically, the venom is a mixture of biologically active substances of high-, medium-, and small molecular weight with a variety of physiological functions. Individual substances may have toxic effects on stung human contributing to certain clinical signs and symptoms of venom poisoning. In the present paper, chemical structure, physiological role and toxicity of particular components of Hymenoptera venom are described.

  6. The venom optimization hypothesis revisited.

    PubMed

    Morgenstern, David; King, Glenn F

    2013-03-01

    Animal venoms are complex chemical mixtures that typically contain hundreds of proteins and non-proteinaceous compounds, resulting in a potent weapon for prey immobilization and predator deterrence. However, because venoms are protein-rich, they come with a high metabolic price tag. The metabolic cost of venom is sufficiently high to result in secondary loss of venom whenever its use becomes non-essential to survival of the animal. The high metabolic cost of venom leads to the prediction that venomous animals may have evolved strategies for minimizing venom expenditure. Indeed, various behaviors have been identified that appear consistent with frugality of venom use. This has led to formulation of the "venom optimization hypothesis" (Wigger et al. (2002) Toxicon 40, 749-752), also known as "venom metering", which postulates that venom is metabolically expensive and therefore used frugally through behavioral control. Here, we review the available data concerning economy of venom use by animals with either ancient or more recently evolved venom systems. We conclude that the convergent nature of the evidence in multiple taxa strongly suggests the existence of evolutionary pressures favoring frugal use of venom. However, there remains an unresolved dichotomy between this economy of venom use and the lavish biochemical complexity of venom, which includes a high degree of functional redundancy. We discuss the evidence for biochemical optimization of venom as a means of resolving this conundrum. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Cross-reactivity between Anisakis spp. and wasp venom allergens.

    PubMed

    Rodríguez-Pérez, Rosa; Monsalve, Rafael I; Galán, Agustin; Perez-Piñar, Teresa; Umpierrez, Ana; Lluch-Bernal, Magdalena; Polo, Francisco; Caballero, María Luisa

    2014-01-01

    Anisakiasis is caused by the consumption of raw or undercooked fish or cephalopods parasitized by live L3 larvae of nematode Anisakis spp. Larvae anchor to stomach mucosa releasing excretion/secretion products which contain the main allergens. It has been described that nematode larvae release venom allergen-like proteins among their excretion/secretion products. We investigated potential cross-reactivity between Anisakis and wasp venom allergens. Two groups of 25 patients each were studied: wasp venom- and Anisakis-allergic patients. Sera from patients were tested by ImmunoCAP, dot-blotting with recombinant Anisakis allergens and ADVIA-Centaur system with Hymenoptera allergens. Cross-reactivity was assessed by IgE immunoblotting inhibition assays. Role of cross-reactive carbohydrate determinants (CCDs) was studied by inhibition with bromelain and periodate treatment. A total of 40% of wasp venom-allergic patients had specific IgE to Anisakis simplex and 20% detected at least one of the Anisakis recombinant allergens tested. Likewise, 44% of Anisakis-allergic patients had specific IgE to Vespula spp. venom and 16% detected at least one of the Hymenoptera allergens tested. Wasp venom-allergic patients detected CCDs in Anisakis extract and peptide epitopes on Anisakis allergens rAni s 1 and rAni s 9, whereas Anisakis-allergic patients only detected CCDs on nVes v 1 allergen from Vespula spp. venom. The only Anisakis allergen inhibited by Vespula venom was rAni s 9. This is the first time that cross-sensitization between wasp venom and Anisakis is described. CCDs are involved in both cases; however, peptide epitopes are only recognized by wasp venom-allergic patients. © 2014 S. Karger AG, Basel.

  8. Elemental analysis of scorpion venoms.

    PubMed

    Al-Asmari, AbdulRahman K; Kunnathodi, Faisal; Al Saadon, Khalid; Idris, Mohammed M

    2016-01-01

    Scorpion venom is a rich source of biomolecules, which can perturb physiological activity of the host on envenomation and may also have a therapeutic potential. Scorpion venoms produced by the columnar cells of venom gland are complex mixture of mucopolysaccharides, neurotoxic peptides and other components. This study was aimed at cataloguing the elemental composition of venoms obtained from medically important scorpions found in the Arabian peninsula. The global elemental composition of the crude venom obtained from Androctonus bicolor, Androctonus crassicauda and Leiurus quinquestriatus scorpions were estimated using ICP-MS analyzer. The study catalogued several chemical elements present in the scorpion venom using ICP-MS total quant analysis and quantitation of nine elements exclusively using appropriate standards. Fifteen chemical elements including sodium, potassium and calcium were found abundantly in the scorpion venom at PPM concentrations. Thirty six chemical elements of different mass ranges were detected in the venom at PPB level. Quantitative analysis of the venoms revealed copper to be the most abundant element in Androctonus sp. venom but at lower level in Leiurus quinquestriatus venom; whereas zinc and manganese was found at higher levels in Leiurus sp. venom but at lower level in Androctonus sp. venom. These data and the concentrations of other different elements present in the various venoms are likely to increase our understanding of the mechanisms of venom activity and their pharmacological potentials.

  9. Elemental analysis of scorpion venoms

    PubMed Central

    Al-Asmari, AbdulRahman K; Kunnathodi, Faisal; Al Saadon, Khalid; Idris, Mohammed M

    2016-01-01

    Scorpion venom is a rich source of biomolecules, which can perturb physiological activity of the host on envenomation and may also have a therapeutic potential. Scorpion venoms produced by the columnar cells of venom gland are complex mixture of mucopolysaccharides, neurotoxic peptides and other components. This study was aimed at cataloguing the elemental composition of venoms obtained from medically important scorpions found in the Arabian peninsula. The global elemental composition of the crude venom obtained from Androctonus bicolor, Androctonus crassicauda and Leiurus quinquestriatus scorpions were estimated using ICP-MS analyzer. The study catalogued several chemical elements present in the scorpion venom using ICP-MS total quant analysis and quantitation of nine elements exclusively using appropriate standards. Fifteen chemical elements including sodium, potassium and calcium were found abundantly in the scorpion venom at PPM concentrations. Thirty six chemical elements of different mass ranges were detected in the venom at PPB level. Quantitative analysis of the venoms revealed copper to be the most abundant element in Androctonus sp. venom but at lower level in Leiurus quinquestriatus venom; whereas zinc and manganese was found at higher levels in Leiurus sp. venom but at lower level in Androctonus sp. venom. These data and the concentrations of other different elements present in the various venoms are likely to increase our understanding of the mechanisms of venom activity and their pharmacological potentials. PMID:27826410

  10. Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails.

    PubMed

    Dutertre, Sébastien; Jin, Ai-Hua; Vetter, Irina; Hamilton, Brett; Sunagar, Kartik; Lavergne, Vincent; Dutertre, Valentin; Fry, Bryan G; Antunes, Agostinho; Venter, Deon J; Alewood, Paul F; Lewis, Richard J

    2014-03-24

    Venomous animals are thought to inject the same combination of toxins for both predation and defence, presumably exploiting conserved target pharmacology across prey and predators. Remarkably, cone snails can rapidly switch between distinct venoms in response to predatory or defensive stimuli. Here, we show that the defence-evoked venom of Conus geographus contains high levels of paralytic toxins that potently block neuromuscular receptors, consistent with its lethal effects on humans. In contrast, C. geographus predation-evoked venom contains prey-specific toxins mostly inactive at human targets. Predation- and defence-evoked venoms originate from the distal and proximal regions of the venom duct, respectively, explaining how different stimuli can generate two distinct venoms. A specialized defensive envenomation strategy is widely evolved across worm, mollusk and fish-hunting cone snails. We propose that defensive toxins, originally evolved in ancestral worm-hunting cone snails to protect against cephalopod and fish predation, have been repurposed in predatory venoms to facilitate diversification to fish and mollusk diets.

  11. Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails

    PubMed Central

    Dutertre, Sébastien; Jin, Ai-Hua; Vetter, Irina; Hamilton, Brett; Sunagar, Kartik; Lavergne, Vincent; Dutertre, Valentin; Fry, Bryan G.; Antunes, Agostinho; Venter, Deon J.; Alewood, Paul F.; Lewis, Richard J.

    2014-01-01

    Venomous animals are thought to inject the same combination of toxins for both predation and defence, presumably exploiting conserved target pharmacology across prey and predators. Remarkably, cone snails can rapidly switch between distinct venoms in response to predatory or defensive stimuli. Here, we show that the defence-evoked venom of Conus geographus contains high levels of paralytic toxins that potently block neuromuscular receptors, consistent with its lethal effects on humans. In contrast, C. geographus predation-evoked venom contains prey-specific toxins mostly inactive at human targets. Predation- and defence-evoked venoms originate from the distal and proximal regions of the venom duct, respectively, explaining how different stimuli can generate two distinct venoms. A specialized defensive envenomation strategy is widely evolved across worm, mollusk and fish-hunting cone snails. We propose that defensive toxins, originally evolved in ancestral worm-hunting cone snails to protect against cephalopod and fish predation, have been repurposed in predatory venoms to facilitate diversification to fish and mollusk diets. PMID:24662800

  12. Mediterranean Jellyfish Venoms: A Review on Scyphomedusae

    PubMed Central

    Mariottini, Gian Luigi; Pane, Luigi

    2010-01-01

    The production of natural toxins is an interesting aspect, which characterizes the physiology and the ecology of a number of marine species that use them for defence/offence purposes. Cnidarians are of particular concern from this point of view; their venoms are contained in specialized structures–the nematocysts–which, after mechanical or chemical stimulation, inject the venom in the prey or in the attacker. Cnidarian stinging is a serious health problem for humans in the zones where extremely venomous jellyfish or anemones are common, such as in temperate and tropical oceanic waters and particularly along several Pacific coasts, and severe cases of envenomation, including also lethal cases mainly induced by cubomedusae, were reported. On the contrary, in the Mediterranean region the problem of jellyfish stings is quite modest, even though they can have anyhow an impact on public health and be of importance from the ecological and economic point of view owing to the implications on ecosystems and on some human activities such as tourism, bathing and fishing. This paper reviews the knowledge about the various aspects related to the occurrence and the stinging of the Mediterranean scyphozoan jellyfish as well as the activity of their venoms. PMID:20479971

  13. Quo Vadis Venomics? A Roadmap to Neglected Venomous Invertebrates

    PubMed Central

    von Reumont, Bjoern Marcus; Campbell, Lahcen I.; Jenner, Ronald A.

    2014-01-01

    Venomics research is being revolutionized by the increased use of sensitive -omics techniques to identify venom toxins and their transcripts in both well studied and neglected venomous taxa. The study of neglected venomous taxa is necessary both for understanding the full diversity of venom systems that have evolved in the animal kingdom, and to robustly answer fundamental questions about the biology and evolution of venoms without the distorting effect that can result from the current bias introduced by some heavily studied taxa. In this review we draw the outlines of a roadmap into the diversity of poorly studied and understood venomous and putatively venomous invertebrates, which together represent tens of thousands of unique venoms. The main groups we discuss are crustaceans, flies, centipedes, non-spider and non-scorpion arachnids, annelids, molluscs, platyhelminths, nemerteans, and echinoderms. We review what is known about the morphology of the venom systems in these groups, the composition of their venoms, and the bioactivities of the venoms to provide researchers with an entry into a large and scattered literature. We conclude with a short discussion of some important methodological aspects that have come to light with the recent use of new -omics techniques in the study of venoms. PMID:25533518

  14. Quo vadis venomics? A roadmap to neglected venomous invertebrates.

    PubMed

    von Reumont, Bjoern Marcus; Campbell, Lahcen I; Jenner, Ronald A

    2014-12-19

    Venomics research is being revolutionized by the increased use of sensitive -omics techniques to identify venom toxins and their transcripts in both well studied and neglected venomous taxa. The study of neglected venomous taxa is necessary both for understanding the full diversity of venom systems that have evolved in the animal kingdom, and to robustly answer fundamental questions about the biology and evolution of venoms without the distorting effect that can result from the current bias introduced by some heavily studied taxa. In this review we draw the outlines of a roadmap into the diversity of poorly studied and understood venomous and putatively venomous invertebrates, which together represent tens of thousands of unique venoms. The main groups we discuss are crustaceans, flies, centipedes, non-spider and non-scorpion arachnids, annelids, molluscs, platyhelminths, nemerteans, and echinoderms. We review what is known about the morphology of the venom systems in these groups, the composition of their venoms, and the bioactivities of the venoms to provide researchers with an entry into a large and scattered literature. We conclude with a short discussion of some important methodological aspects that have come to light with the recent use of new -omics techniques in the study of venoms.

  15. Dietary breadth is positively correlated with venom complexity in cone snails.

    PubMed

    Phuong, Mark A; Mahardika, Gusti N; Alfaro, Michael E

    2016-05-26

    Although diet is believed to be a major factor underlying the evolution of venom, few comparative studies examine both venom composition and diet across a radiation of venomous species. Cone snails within the family, Conidae, comprise more than 700 species of carnivorous marine snails that capture their prey by using a cocktail of venomous neurotoxins (conotoxins or conopeptides). Venom composition across species has been previously hypothesized to be shaped by (a) prey taxonomic class (i.e., worms, molluscs, or fish) and (b) dietary breadth. We tested these hypotheses under a comparative phylogenetic framework using ecological data from past studies in conjunction with venom duct transcriptomes sequenced from 12 phylogenetically disparate cone snail species, including 10 vermivores (worm-eating), one molluscivore, and one generalist. We discovered 2223 unique conotoxin precursor peptides that encoded 1864 unique mature toxins across all species, >90 % of which are new to this study. In addition, we identified two novel gene superfamilies and 16 novel cysteine frameworks. Each species exhibited unique venom profiles, with venom composition and expression patterns among species dominated by a restricted set of gene superfamilies and mature toxins. In contrast with the dominant paradigm for interpreting Conidae venom evolution, prey taxonomic class did not predict venom composition patterns among species. We also found a significant positive relationship between dietary breadth and measures of conotoxin complexity. The poor performance of prey taxonomic class in predicting venom components suggests that cone snails have either evolved species-specific expression patterns likely as a consequence of the rapid evolution of conotoxin genes, or that traditional means of categorizing prey type (i.e., worms, mollusc, or fish) and conotoxins (i.e., by gene superfamily) do not accurately encapsulate evolutionary dynamics between diet and venom composition. We also show that

  16. Comparative Venomics Reveals the Complex Prey Capture Strategy of the Piscivorous Cone Snail Conus catus.

    PubMed

    Himaya, S W A; Jin, Ai-Hua; Dutertre, Sébastien; Giacomotto, Jean; Mohialdeen, Hoshyar; Vetter, Irina; Alewood, Paul F; Lewis, Richard J

    2015-10-02

    Venomous marine cone snails produce a unique and remarkably diverse range of venom peptides (conotoxins and conopeptides) that have proven to be invaluable as pharmacological probes and leads to new therapies. Conus catus is a hook-and-line fish hunter from clade I, with ∼20 conotoxins identified, including the analgesic ω-conotoxin CVID (AM336). The current study unravels the venom composition of C. catus with tandem mass spectrometry and 454 sequencing data. From the venom gland transcriptome, 104 precursors were recovered from 11 superfamilies, with superfamily A (especially κA-) conotoxins dominating (77%) their venom. Proteomic analysis confirmed that κA-conotoxins dominated the predation-evoked milked venom of each of six C. catus analyzed and revealed remarkable intraspecific variation in both the intensity and type of conotoxins. High-throughput FLIPR assays revealed that the predation-evoked venom contained a range of conotoxins targeting the nAChR, Cav, and Nav ion channels, consistent with α- and ω-conotoxins being used for predation by C. catus. However, the κA-conotoxins did not act at these targets but induced potent and rapid immobilization followed by bursts of activity and finally paralysis when injected intramuscularly in zebrafish. Our venomics approach revealed the complexity of the envenomation strategy used by C. catus, which contains a mix of both excitatory and inhibitory venom peptides.

  17. Venom variation during prey capture by the cone snail, Conus textile.

    PubMed

    Prator, Cecilia A; Murayama, Kellee M; Schulz, Joseph R

    2014-01-01

    Observations of the mollusc-hunting cone snail Conus textile during feeding reveal that prey are often stung multiple times in succession. While studies on the venom peptides injected by fish-hunting cone snails have become common, these approaches have not been widely applied to the analysis of the injected venoms from mollusc-hunters. We have successfully obtained multiple injected venom samples from C. textile individuals, allowing us to investigate venom compositional variation during prey capture. Our studies indicate that C. textile individuals alter the composition of prey-injected venom peptides during single feeding events. The qualitative results obtained by MALDI-ToF mass spectrometry are mirrored by quantitative changes in venom composition observed by reverse-phase high performance liquid chromatography. While it is unclear why mollusc-hunting cone snails inject prey multiple times prior to engulfment, our study establishes for the first time a link between this behavior and compositional changes of the venom during prey capture. Changes in venom composition during hunting may represent a multi-step strategy utilized by these venomous animals to slow and incapacitate prey prior to engulfment.

  18. Venom Variation during Prey Capture by the Cone Snail, Conus textile

    PubMed Central

    Prator, Cecilia A.; Murayama, Kellee M.; Schulz, Joseph R.

    2014-01-01

    Observations of the mollusc-hunting cone snail Conus textile during feeding reveal that prey are often stung multiple times in succession. While studies on the venom peptides injected by fish-hunting cone snails have become common, these approaches have not been widely applied to the analysis of the injected venoms from mollusc-hunters. We have successfully obtained multiple injected venom samples from C. textile individuals, allowing us to investigate venom compositional variation during prey capture. Our studies indicate that C. textile individuals alter the composition of prey-injected venom peptides during single feeding events. The qualitative results obtained by MALDI-ToF mass spectrometry are mirrored by quantitative changes in venom composition observed by reverse-phase high performance liquid chromatography. While it is unclear why mollusc-hunting cone snails inject prey multiple times prior to engulfment, our study establishes for the first time a link between this behavior and compositional changes of the venom during prey capture. Changes in venom composition during hunting may represent a multi-step strategy utilized by these venomous animals to slow and incapacitate prey prior to engulfment. PMID:24940882

  19. [Venoms and medical research].

    PubMed

    Ducancel, Frédéric

    2016-01-01

    Animal venoms are complex chemical cocktails, comprising a wide range of biologically active reticulated peptides that target with high selectivity and efficacy a variety of enzymes, membrane receptors, ion channels...Venoms can therefore be seen as large natural libraries of biologically active molecules that are continuously selected and highly refined by the evolution process, up to the point where every molecule is endowed with pharmacological properties that are highly valuable in the context of human use and drug development. Therefore, venom exploration constitutes a prerequisite to drug discovery. However, mass spectrometry and transcriptomics via NGS (Next Generation Sequencing) studies have shown the presence of up to 1000 peptides in the venom of single species of cone snails and spiders. Therefore the global animal venom resource can be seen as a collection of more than 50 to 100 000 000 peptides and proteins of which only ~5000 are known. That extraordinary "Eldorado" of bio-optimized compounds justifies the development of more global and cutting-edge strategies and technologies to explore this resource more efficiently than actually. De novo developed approaches and recently obtained results will be described. © Société de Biologie, 2016.

  20. Comparative study of the toxic effects of Chrysaora quinquecirrha (Cnidaria: Scyphozoa) and Chironex fleckeri (Cnidaria: Cubozoa) venoms using cell-based assays.

    PubMed

    Ponce, Dalia; Brinkman, Diane L; Luna-Ramírez, Karen; Wright, Christine E; Dorantes-Aranda, Juan José

    2015-11-01

    The venoms of jellyfish cause toxic effects in diverse biological systems that can trigger local and systemic reactions. In this study, the cytotoxic and cytolytic effects of Chrysaora quinquecirrha and Chironex fleckeri venoms were assessed and compared using three in vitro assays. Venoms from both species were cytotoxic to fish gill cells and rat cardiomyocytes, and cytolytic in sheep erythrocytes. Both venoms decreased cell viability in a concentration-dependent manner; however, the greatest difference in venom potencies was observed in the fish gill cell line, wherein C. fleckeri was 12.2- (P = 0.0005) and 35.7-fold (P < 0.0001) more potently cytotoxic than C. quinquecirrha venom with 30 min and 120 min cell exposure periods, respectively. Gill cells and rat cardiomyocytes exposed to venoms showed morphological changes characterised by cell shrinkage, clumping and detachment. The cytotoxic effects of venoms may be caused by a group of toxic proteins that have been previously identified in C. fleckeri and other cubozoan jellyfish species. In this study, proteins homologous to CfTX-1 and CfTX-2 toxins from C. fleckeri and CqTX-A toxin from Chironex yamaguchii were identified in C. quinquecirrha venom using tandem mass spectrometry. The presence and relative abundance of these proteins may explain the differences in venom potency between cubozoan and scyphozoan jellyfish and may reflect their importance in the action of venoms.

  1. Bioactive Mimetics of Conotoxins and other Venom Peptides

    PubMed Central

    Duggan, Peter J.; Tuck, Kellie L.

    2015-01-01

    Ziconotide (Prialt®), a synthetic version of the peptide ω-conotoxin MVIIA found in the venom of a fish-hunting marine cone snail Conus magnus, is one of very few drugs effective in the treatment of intractable chronic pain. However, its intrathecal mode of delivery and narrow therapeutic window cause complications for patients. This review will summarize progress in the development of small molecule, non-peptidic mimics of Conotoxins and a small number of other venom peptides. This will include a description of how some of the initially designed mimics have been modified to improve their drug-like properties. PMID:26501323

  2. Understanding and utilising mammalian venom via a platypus venom transcriptome.

    PubMed

    Whittington, Camilla M; Koh, Jennifer M S; Warren, Wesley C; Papenfuss, Anthony T; Torres, Allan M; Kuchel, Philip W; Belov, Katherine

    2009-03-06

    Only five mammalian species are known to be venomous, and while a large amount of research has been carried out on reptile venom, mammalian venom has been poorly studied to date. Here we describe the status of current research into the venom of the platypus, a semi-aquatic egg-laying Australian mammal, and discuss our approach to platypus venom transcriptomics. We propose that such construction and analysis of mammalian venom transcriptomes from small samples of venom gland, in tandem with proteomics studies, will allow the identification of the full range of mammalian venom components. Functional studies and pharmacological evaluation of the identified toxins will then lay the foundations for the future development of novel biomedical substances. A large range of useful molecules have already been identified in snake venom, and many of these are currently in use in human medicine. It is therefore hoped that this basic research to identify the constituents of platypus venom will eventually yield novel drugs and new targets for painkillers.

  3. Natriuretic peptide drug leads from snake venom.

    PubMed

    Vink, S; Jin, A H; Poth, K J; Head, G A; Alewood, P F

    2012-03-15

    Natriuretic peptides are body fluid volume modulators, termed natriuretic peptides due to a role in natriuresis and diuresis. The three mammalian NPs, atrial natriuretic peptide (ANP), brain or b-type natriuretic peptide (BNP) and c-type natriuretic peptide (CNP), have been extensively investigated for their use as therapeutic agents for the treatment of cardiovascular diseases. Although effective, short half-lives and renal side effects limit their use. In approximately 30 years of research, NPs have been discovered in many vertebrates including mammals, amphibians, reptiles and fish, with plants and, more recently, bacteria also being found to possess NPs. Reptiles have produced some of the more interesting NPs, with dendroaspis natriuretic peptide (DNP), which was isolated from the venom of the green mamba (Dendroaspis angusticeps), having greater potency and increased stability as compared to the mammalian family members, and taipan natriuretic peptide c (TNPc), which was isolated from the venom of the inland taipan (Oxyuranus microlepidotus) displaying similar activity to ANP and DNP at rat natriuretic peptide receptor A. Although promising, more research is required in this field to develop therapeutics that overcome receptor-mediated clearance, and potential toxicity issues. This review investigates the use of snake venom NPs as therapeutic drug leads. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Bioinformatics-Aided Venomics

    PubMed Central

    Kaas, Quentin; Craik, David J.

    2015-01-01

    Venomics is a modern approach that combines transcriptomics and proteomics to explore the toxin content of venoms. This review will give an overview of computational approaches that have been created to classify and consolidate venomics data, as well as algorithms that have helped discovery and analysis of toxin nucleic acid and protein sequences, toxin three-dimensional structures and toxin functions. Bioinformatics is used to tackle specific challenges associated with the identification and annotations of toxins. Recognizing toxin transcript sequences among second generation sequencing data cannot rely only on basic sequence similarity because toxins are highly divergent. Mass spectrometry sequencing of mature toxins is challenging because toxins can display a large number of post-translational modifications. Identifying the mature toxin region in toxin precursor sequences requires the prediction of the cleavage sites of proprotein convertases, most of which are unknown or not well characterized. Tracing the evolutionary relationships between toxins should consider specific mechanisms of rapid evolution as well as interactions between predatory animals and prey. Rapidly determining the activity of toxins is the main bottleneck in venomics discovery, but some recent bioinformatics and molecular modeling approaches give hope that accurate predictions of toxin specificity could be made in the near future. PMID:26110505

  5. The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms.

    PubMed

    Fry, Bryan G; Roelants, Kim; Champagne, Donald E; Scheib, Holger; Tyndall, Joel D A; King, Glenn F; Nevalainen, Timo J; Norman, Janette A; Lewis, Richard J; Norton, Raymond S; Renjifo, Camila; de la Vega, Ricardo C Rodríguez

    2009-01-01

    Throughout evolution, numerous proteins have been convergently recruited into the venoms of various animals, including centipedes, cephalopods, cone snails, fish, insects (several independent venom systems), platypus, scorpions, shrews, spiders, toxicoferan reptiles (lizards and snakes), and sea anemones. The protein scaffolds utilized convergently have included AVIT/colipase/prokineticin, CAP, chitinase, cystatin, defensins, hyaluronidase, Kunitz, lectin, lipocalin, natriuretic peptide, peptidase S1, phospholipase A(2), sphingomyelinase D, and SPRY. Many of these same venom protein types have also been convergently recruited for use in the hematophagous gland secretions of invertebrates (e.g., fleas, leeches, kissing bugs, mosquitoes, and ticks) and vertebrates (e.g., vampire bats). Here, we discuss a number of overarching structural, functional, and evolutionary generalities of the protein families from which these toxins have been frequently recruited and propose a revised and expanded working definition for venom. Given the large number of striking similarities between the protein compositions of conventional venoms and hematophagous secretions, we argue that the latter should also fall under the same definition.

  6. A new bioassay reveals mollusc-specific toxicity in molluscivorous Conus venoms.

    PubMed

    Fainzilber, M; Zlotkin, E

    1992-04-01

    Contraction of the foot pedal of a limpet snail is described as a new and quantifiable bioassay for mollusc paralysis. This bioassay was used for screening the venoms of seven different species of Conus snails. Comparison of the results of the limpet assay with those obtained from fish and blowflies shows a correlation between the feeding specificities and venom toxicities of these Conidae. The limpet bioassay should be useful for identification and monitoring of the purification of new toxins active on molluscan systems.

  7. A non-proteinaceous toxin from the venomous spines of the lionfish Pterois volitans (Linnaeus).

    PubMed

    Nair, M S; Cheung, P; Leong, I; Ruggieri, G D

    1985-01-01

    The venomous spines of P. volitans contain a non-proteinaceous ichthyotoxin of low molecular weight. This toxin could be isolated only from spines excised from the living fish; the toxin is apparently destroyed following death, as the extracts of the spines of the dead fish were non-toxic.

  8. Scorpion venoms in gastric cancer

    PubMed Central

    Zhang, Xiao-Ying; Zhang, Pei-Ying

    2016-01-01

    Venom secretions from snakes, scorpions, spiders and bees, have been widely applied in traditional medicine and current biopharmaceutical research. Possession of anticancer potential is another novel discovery for animal venoms and toxins. An increasing number of studies have shown the anticancer effects of venoms and toxins of snakes, and scorpions in vitro and in vivo, which were achieved mainly through the inhibition of cancer growth, arrest of cell cycle, induction of apoptosis and suppression of cancer metastasis. However, more evidence is needed to support this concept and the mechanisms of anticancer actions are not clearly understood. The present review is focused on the recant updates on anticancer venom research. PMID:27900054

  9. [Insect venom allergies].

    PubMed

    Przybilla, Bernhard; Ruëff, Franziska

    2003-10-01

    Systemic IgE-mediated immediate type reactions (anaphylaxis) due to honeybee or vespid stings are potentially life-threatening; they are reported in up to 5% of the general population. Insect venom allergy is diagnosed by history, skin testing and measurement of insect venom-specific serum IgE; sometimes additional tests are needed. The diagnosis is based on the history of a systemic allergic immediate type sting reaction, without such a medical history any other "positive" test results are irrelevant. Nearly always, patients with systemic allergic sting reactions can be protected from further episodes of anaphylaxis by a carefully performed hyposensitization (specific immunotherapy). If therapeutic efficacy has been proven by tolerance of a re-sting, hyposensitization can be frequently stopped after 3 to 5 years. Patients with a particular risk of frequent re-stings or of very severe sting reactions may have to be treated for a longer time, some of them even life-long.

  10. Transcriptome and proteome of Conus planorbis identify the nicotinic receptors as primary target for the defensive venom.

    PubMed

    Jin, Ai-Hua; Vetter, Irina; Himaya, Siddhihalu W A; Alewood, Paul F; Lewis, Richard J; Dutertre, Sébastien

    2015-12-01

    Most venomous predators have evolved complex venom primarily to immobilize their prey and secondarily to defend against predators. In a new paradigm, carnivorous marine gastropods of the genus Conus were shown to rapidly and reversibly switch between two types of venoms in response to predatory or defensive stimulus, suggesting that the defensive use of venom may have a more important role in venom evolution and specialization than previously thought. To further investigate this phenomenon, the defensive repertoire of a vermivorous species, Conus planorbis, was deciphered using second-generation sequencing coupled to high-throughput proteomics. The venom gland transcriptome of C. planorbis revealed 182 unique conotoxin precursors from 25 gene superfamilies, with superfamily T dominating in terms of read and paralog numbers. Analysis of the defense-evoked venom revealed that this vermivorous species uses a similarly complex arsenal to deter aggressors as more recently evolved fish- and mollusk-hunting species, with MS/MS validating 23 conotoxin sequences from six superfamilies. Pharmacological characterization of the defensive venom on human receptors identified the nicotinic acetylcholine receptors as a primary target. This work provides the first insights into the composition and biological activity of specifically evolved defensive venoms in vermivorous cone snails. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Analysis of the inflammatory reaction induced by the catfish (Cathorops spixii) venoms.

    PubMed

    Junqueira, Marcos Emerson Pinheiro; Grund, Lidiane Zito; Orii, Noêmia M; Saraiva, Tânia Cristina; de Magalhães Lopes, Carlos Alberto; Lima, Carla; Lopes-Ferreira, Mônica

    2007-06-01

    Cathorops spixii is one of the most abundant venomous fish of the southeastern coast of the State of São Paulo, and consequently causes a great part of the accidents seen there. The accidents affect mainly fishermen, swimmers and tourists and are characterized by punctiform or wide wounds, erythema, edema, pain, sudoresis, indisposition, fever, nausea, vomiting and secondary infection. The objective of this work was to characterize the inflammatory response induced in mice by both venoms (mucus and sting) of the catfish C. spixii. Our results demonstrated that both venoms induced a great number of rolling and adherent leukocytes in the post-capillary venules of cremaster muscle of mice, and an increase in the vascular permeability in peritoneal cavity. Mucus induced the recruitment of neutrophils immediately after injection followed later by macrophage infiltration. In contrast, the cellular infiltration elicited by sting venom was rapidly resolved. The peritonitis reaction provoked by venoms was characterized by cytokine (IL-6), chemokines (MCP-1 and KC) or lipid mediator (LTB4) production in the peritoneal cavity. The macrophages from 7-day mucus venom-induced exudates upon in vitro mucus venom stimulation, expressed CD11c x MHC class II and release bioactive IL-12p70. On the other hand, sting venom-elicited peritoneal macrophages lost the ability to differentiate into dendritic cells, following re-stimulation in vitro with sting venom, they do not express CD11c, nor do they exhibit sufficient levels of MHC class II. In conclusion, both types of venoms (mucus or sting) promote inflammatory reaction with different profiles, and the inflammatory reaction induced by the first was characterized by antigen persistence in peritoneal cavity that allowed the activation of phagocytic cells with capacity of antigenic presentation.

  12. Accessing Novel Conoidean Venoms: Biodiverse Lumun-lumun Marine Communities, An Untapped Biological and Toxinological Resource

    PubMed Central

    Seronay, Romell A.; Fedosov, Alexander E.; Astilla, Mary Anne; Watkins, Maren; Saguil, Noel; Heralde, Francisco M.; Tagaro, Sheila; Poppe, Guido T.; Aliño, Porfirio M.; Oliverio, Marco; Kantor, Yuri I.; Concepcion, Gisela P.; Olivera, Baldomero M.

    2010-01-01

    Cone snail venoms have yielded pharmacologically-active natural products of exceptional scientific interest. However, cone snails are a small minority of venomous molluscan biodiversity, the vast majority being tiny venomous morphospecies in the family Turridae. A novel method called lumun-lumun opens access to these micromolluscs and their venoms. Old fishing nets are anchored to the sea bottom for a period of 1–6 months and marine biotas rich in small molluscs are established. In a single lumun-lumun community, we found a remarkable gastropod biodiversity (155 morphospecies). Venomous predators belonging to the superfamily Conoidea (36 morphospecies) were the largest group, the majority being micromolluscs in the family Turridae. We carried out an initial analysis of the most abundant of the turrid morphospecies recovered, Clathurella (Lienardia) cincta (Dunker, 1871). In contrast to all cDNA clones characterized from cone snail venom ducts, one of the C. cincta clones identified encoded two different peptide precursors presumably translated from a single mRNA. The prospect of easily accessing so many different morphospecies of venomous marine snails raises intriguing toxinological possibilities: the 36 conoidean morphospecies in this one net alone have the potential to yield thousands of novel pharmacologically-active compounds. PMID:20005243

  13. Accessing novel conoidean venoms: Biodiverse lumun-lumun marine communities, an untapped biological and toxinological resource.

    PubMed

    Seronay, Romell A; Fedosov, Alexander E; Astilla, Mary Anne Q; Watkins, Maren; Saguil, Noel; Heralde, Francisco M; Tagaro, Sheila; Poppe, Guido T; Aliño, Porfirio M; Oliverio, Marco; Kantor, Yuri I; Concepcion, Gisela P; Olivera, Baldomero M

    2010-12-15

    Cone snail venoms have yielded pharmacologically active natural products of exceptional scientific interest. However, cone snails are a small minority of venomous molluscan biodiversity, the vast majority being tiny venomous morphospecies in the family Turridae. A novel method called lumun-lumun opens access to these micromolluscs and their venoms. Old fishing nets are anchored to the sea bottom for a period of 1-6months and marine biotas rich in small molluscs are established. In a single lumun-lumun community, we found a remarkable gastropod biodiversity (155 morphospecies). Venomous predators belonging to the superfamily Conoidea (36 morphospecies) were the largest group, the majority being micromolluscs in the family Turridae. We carried out an initial analysis of the most abundant of the turrid morphospecies recovered, Clathurella (Lienardia) cincta (Dunker, 1871). In contrast to all cDNA clones characterized from cone snail venom ducts, one of the C. cincta clones identified encoded two different peptide precursors presumably translated from a single mRNA. The prospect of easily accessing so many different morphospecies of venomous marine snails raises intriguing toxinological possibilities: the 36 conoidean morphospecies in this one net alone have the potential to yield thousands of novel pharmacologically active compounds.

  14. Unusual stability of messenger RNA in snake venom reveals gene expression dynamics of venom replenishment.

    PubMed

    Currier, Rachel B; Calvete, Juan J; Sanz, Libia; Harrison, Robert A; Rowley, Paul D; Wagstaff, Simon C

    2012-01-01

    Venom is a critical evolutionary innovation enabling venomous snakes to become successful limbless predators; it is therefore vital that venomous snakes possess a highly efficient venom production and delivery system to maintain their predatory arsenal. Here, we exploit the unusual stability of messenger RNA in venom to conduct, for the first time, quantitative PCR to characterise the dynamics of gene expression of newly synthesised venom proteins following venom depletion. Quantitative PCR directly from venom enables real-time dynamic studies of gene expression in the same animals because it circumvents the conventional requirement to sacrifice snakes to extract mRNA from dissected venom glands. Using qPCR and proteomic analysis, we show that gene expression and protein re-synthesis triggered by venom expulsion peaks between days 3-7 of the cycle of venom replenishment, with different protein families expressed in parallel. We demonstrate that venom re-synthesis occurs very rapidly following depletion of venom stores, presumably to ensure venomous snakes retain their ability to efficiently predate and remain defended from predators. The stability of mRNA in venom is biologically fascinating, and could significantly empower venom research by expanding opportunities to produce transcriptomes from historical venom stocks and rare or endangered venomous species, for new therapeutic, diagnostic and evolutionary studies.

  15. Cryptic Diversity and Venom Glands in Western Atlantic Clingfishes of the Genus Acyrtus (Teleostei: Gobiesocidae)

    PubMed Central

    Conway, Kevin W.; Baldwin, Carole; White, Macaulay D.

    2014-01-01

    Examination of genetic data (mitochondrial cytochrome c oxidase I) for western Atlantic clingfishes revealed two distinct lineages within a group of individuals originally identified as Acyrtus artius. Subsequent investigation of preserved voucher specimens was conducted to reconcile the genetic data and the existing classification, which is based on morphology. In addition to discovering that one of the genetic lineages is an undescribed species, which we describe as Acyrtus lanthanum, new species, we found that the nominal species Acyrtus artius has a putative venom gland associated with the subopercle that has been overlooked since the species was described nearly 60 years ago. The new species lacks the subopercular gland as does Acyrtus rubiginosus, but one is present in the related Arcos nudus. Venom glands have not been reported previously for the Gobiesocidae, and the venom gland described herein for Acyrtus and Arcos represents the first example in teleost fishes of a venom gland associated with the subopercle. PMID:24825326

  16. Polymerized soluble venom--human serum albumin

    SciTech Connect

    Patterson, R.; Suszko, I.M.; Grammer, L.C.

    1985-03-01

    Extensive previous studies have demonstrated that attempts to produce polymers of Hymenoptera venoms for human immunotherapy resulted in insoluble precipitates that could be injected with safety but with very limited immunogenicity in allergic patients. We now report soluble polymers prepared by conjugating bee venom with human serum albumin with glutaraldehyde. The bee venom-albumin polymer (BVAP) preparation was fractionated on Sephacryl S-300 to have a molecular weight range higher than catalase. /sup 125/I-labeled bee venom phospholipase A was almost completely incorporated into BVAP. Rabbit antibody responses to bee venom and bee venom phospholipase A were induced by BVAP. Human antisera against bee venom were absorbed by BVAP. No new antigenic determinants on BVAP were present as evidenced by absorption of antisera against BVAP by bee venom and albumin. BVAP has potential immunotherapeutic value in patients with anaphylactic sensitivity to bee venom.

  17. Discontinuing venom immunotherapy: extended observations.

    PubMed

    Golden, D B; Kwiterovich, K A; Kagey-Sobotka, A; Lichtenstein, L M

    1998-03-01

    Our studies of discontinuing venom immunotherapy after at least 5 years have led to the conclusion that the residual risk of a systemic reaction to a sting was in the range of 5% to 10% in adults, and no severe or life-threatening reaction occurred with 270 challenge stings in 74 patients after 1 to 5 years without venom immunotherapy. The objective of this study was to extend our observation of patients who discontinue venom immunotherapy over 5 to 10 years and to determine which patients are at higher risk for a reaction. Patients who discontinued venom immunotherapy were surveyed for 3 consecutive years to determine the frequency of systemic reactions to field stings and the fate of venom sensitivity. The evaluation included the 74 patients previously studied (group 1) and 51 additional patients followed after stopping therapy in our clinical center (group 2). Of the original 74 patients, 11 had field stings again after 3 to 7 years without venom immunotherapy, with one systemic reaction (dyspnea). Of the 51 patients in the other group, 15 were stung, of whom four (26%) had systemic reactions, including respiratory symptoms requiring epinephrine. Review of group 1 and group 2 revealed that half of the patients who had systemic reactions to a sting after stopping venom immunotherapy had a history of a systemic reaction occurring during venom immunotherapy (to an injection or a sting). Systemic reactions occurred in three patients who had negative skin test reactions; all three had very low but detectable venom-specific serum IgE antibody levels as determined by RAST and had a history of systemic reactions during venom immunotherapy. Greater severity of the pretreatment reaction was not associated with higher frequency of reaction to stings after stopping therapy but was associated with greater severity if a reaction did occur. Venom immunotherapy (yellow jacket/mixed vespid) in adults can be discontinued after 5 to 6 years with a 5% to 10% residual risk of a

  18. A Polychaete's powerful punch: venom gland transcriptomics of Glycera reveals a complex cocktail of toxin homologs.

    PubMed

    von Reumont, Björn M; Campbell, Lahcen I; Richter, Sandy; Hering, Lars; Sykes, Dan; Hetmank, Jörg; Jenner, Ronald A; Bleidorn, Christoph

    2014-09-05

    Glycerids are marine annelids commonly known as bloodworms. Bloodworms have an eversible proboscis adorned with jaws connected to venom glands. Bloodworms prey on invertebrates, and it is known that the venom glands produce compounds that can induce toxic effects in animals. Yet, none of these putative toxins has been characterized on a molecular basis. Here we present the transcriptomic profiles of the venom glands of three species of bloodworm, Glycera dibranchiata, Glycera fallax and Glycera tridactyla, as well as the body tissue of G. tridactyla. The venom glands express a complex mixture of transcripts coding for putative toxin precursors. These transcripts represent 20 known toxin classes that have been convergently recruited into animal venoms, as well as transcripts potentially coding for Glycera-specific toxins. The toxins represent five functional categories: Pore-forming and membrane-disrupting toxins, neurotoxins, protease inhibitors, other enzymes, and CAP domain toxins. Many of the transcripts coding for putative Glycera toxins belong to classes that have been widely recruited into venoms, but some are homologs of toxins previously only known from the venoms of scorpaeniform fish and monotremes (stonustoxin-like toxin), turrid gastropods (turripeptide-like peptides), and sea anemones (gigantoxin I-like neurotoxin). This complex mixture of toxin homologs suggests that bloodworms employ venom while predating on macroscopic prey, casting doubt on the previously widespread opinion that G. dibranchiata is a detritivore. Our results further show that researchers should be aware that different assembly methods, as well as different methods of homology prediction, can influence the transcriptomic profiling of venom glands. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. Polypeptide toxins from animal venoms.

    PubMed

    Kozlov, Sergey A

    2007-01-01

    In the course of evolution, venomous animals developed highly specialized venomous systems that provided for drastic increase in hunting and defense efficiency. Venoms of a vast number of animal species represent complex mixtures of compounds such as ions, biogenic amines, polyamines, polypeptide neurotoxins, cytolytic peptides, enzymes, etc. that exert different functions. Natural toxins are sequentially variable molecules that are very stable structurally and produce pronounced biological effects on molecular targets. High activity made them very attractive in terms of novel structure discovery and characterization. In the present review we draw attention to the structure of polypeptide molecules preferably in the 2-12 kDa molecular mass range produced by various venomous animals that were published in patent literature. The structures were reviewed on the basis of functional relation to molecular targets. We also compared the sequence information from patents with Uniprot and other protein databanks to define structures that were patented but missing from the public databases.

  20. Intraspecific variations in Conus purpurascens injected venom using LC/MALDI-TOF-MS and LC-ESI-TripleTOF-MS.

    PubMed

    Rodriguez, Alena M; Dutertre, Sebastien; Lewis, Richard J; Marí, Frank

    2015-08-01

    The venom of cone snails is composed of highly modified peptides (conopeptides) that target a variety of ion channels and receptors. The venom of these marine gastropods represents a largely untapped resource of bioactive compounds of potential pharmaceutical value. Here, we use a combination of bioanalytical techniques to uncover the extent of venom expression variability in Conus purpurascens, a fish-hunting cone snail species. The injected venom of nine specimens of C. purpurascens was separated by reversed-phase high-performance liquid chromatography (RP-HPLC), and fractions were analyzed using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) in parallel with liquid chromatography-electrospray ionization (LC-ESI)-TripleTOF-MS to compare standard analytical protocols used in preparative bioassay-guided fractionations with a deeper peptidomic analysis. Here, we show that C. purpurascens exhibits pronounced intraspecific venom variability. RP-HPLC fractionation followed by MALDI-TOF-MS analysis of the injected venom of these nine specimens identified 463 distinct masses, with none common to all specimens. Using LC-ESI-TripleTOF-MS, the injected venom of these nine specimens yielded a total of 5517 unique masses. We also compare the injected venom of two specimens with their corresponding dissected venom. We found 2566 and 1990 unique masses for the dissected venom compared to 941 and 1959 masses in their corresponding injected venom. Of these, 742 and 1004 masses overlapped between the dissected and injected venom, respectively. The results indicate that larger conopeptide libraries can be assessed by studying multiple individuals of a given cone snail species. This expanded library of conopeptides enhances the opportunities for discovery of molecular modulators with direct relevance to human therapeutics. Graphical Abstract The venom of cone snails are extraordinarily complex mixtures of highly modified peptides. Venom

  1. Animal venoms as antimicrobial agents.

    PubMed

    Perumal Samy, Ramar; Stiles, Bradley G; Franco, Octavio L; Sethi, Gautam; Lim, Lina H K

    2017-06-15

    Hospitals are breeding grounds for many life-threatening bacteria worldwide. Clinically associated gram-positive bacteria such as Staphylococcus aureus/methicillin-resistant S. aureus and many others increase the risk of severe mortality and morbidity. The failure of antibiotics to kill various pathogens due to bacterial resistance highlights the urgent need to develop novel, potent, and less toxic agents from natural sources against various infectious agents. Currently, several promising classes of natural molecules from snake (terrestrial and sea), scorpion, spider, honey bee and wasp venoms hold promise as rich sources of chemotherapeutics against infectious pathogens. Interestingly, snake venom-derived synthetic peptide/snake cathelicidin not only has potent antimicrobial and wound-repair activity but is highly stable and safe. Such molecules are promising candidates for novel venom-based drugs against S. aureus infections. The structure of animal venom proteins/peptides (cysteine rich) consists of hydrophobic α-helices or β-sheets that produce lethal pores and membrane-damaging effects on bacteria. All these antimicrobial peptides are under early experimental or pre-clinical stages of development. It is therefore important to employ novel tools for the design and the development of new antibiotics from the untapped animal venoms of snake, scorpion, and spider for treating resistant pathogens. To date, snail venom toxins have shown little antibiotic potency against human pathogens. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Preclinical testing of Peruvian anti-bothropic anti-venom against Bothrops andianus snake venom.

    PubMed

    Schneider, Francisco S; Starling, Maria C; Duarte, Clara G; Machado de Avila, Ricardo; Kalapothakis, Evanguedes; Silva Suarez, Walter; Tintaya, Benigno; Flores Garrido, Karin; Seraylan Ormachea, Silvia; Yarleque, Armando; Bonilla, César; Chávez-Olórtegui, Carlos

    2012-11-01

    Bothrops andianus is a venomous snake found in the area of Machu Picchu (Peru). Its venom is not included in the antigenic pool used for production of the Peruvian anti-bothropic anti-venom. B. andianus venom can elicit many biological effects such as hemorrhage, hemolysis, proteolytic activity and lethality. The Peruvian anti-bothropic anti-venom displays consistent cross-reactivity with B. andianus venom, by ELISA and Western Blotting and is also effective in neutralizing the venom's toxic activities. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. High-resolution proteomic profiling of spider venom: expanding the toxin diversity of Phoneutria nigriventer venom.

    PubMed

    Liberato, Tarcísio; Troncone, Lanfranco Ranieri Paolo; Yamashiro, Edson T; Serrano, Solange M T; Zelanis, André

    2016-03-01

    Here we present a proteomic characterization of Phoneutria nigriventer venom. A shotgun proteomic approach allowed the identification, for the first time, of O-glycosyl hydrolases (chitinases) in P. nigriventer venom. The electrophoretic profiles under nonreducing and reducing conditions, and protein identification by mass spectrometry, indicated the presence of oligomeric toxin structures in the venom. Complementary proteomic approaches allowed for a qualitative and semi-quantitative profiling of P. nigriventer venom complexity, expanding its known venom proteome diversity.

  4. Detection and Identification of Vipera Russelli Venom

    DTIC Science & Technology

    1990-01-01

    adapted for the detection and identification of vier russelli venom. The assay sensitivity was observed to be 10-13 g m7’. Venoms from snakes of the Vipera...Enzyme-linked Immunosorbent Assay (FELISA) has been adapted for the detection and identification of Vipera russelli venom. The assay sensitivity was...observed to _13 _ be 10 g ml . Venoms from snakes of the Vipera group exhibited a high degree of cross reactivity when tested with the anti- body

  5. Extraction of venom and venom gland microdissections from spiders for proteomic and transcriptomic analyses.

    PubMed

    Garb, Jessica E

    2014-11-03

    Venoms are chemically complex secretions typically comprising numerous proteins and peptides with varied physiological activities. Functional characterization of venom proteins has important biomedical applications, including the identification of drug leads or probes for cellular receptors. Spiders are the most species rich clade of venomous organisms, but the venoms of only a few species are well-understood, in part due to the difficulty associated with collecting minute quantities of venom from small animals. This paper presents a protocol for the collection of venom from spiders using electrical stimulation, demonstrating the procedure on the Western black widow (Latrodectus hesperus). The collected venom is useful for varied downstream analyses including direct protein identification via mass spectrometry, functional assays, and stimulation of venom gene expression for transcriptomic studies. This technique has the advantage over protocols that isolate venom from whole gland homogenates, which do not separate genuine venom components from cellular proteins that are not secreted as part of the venom. Representative results demonstrate the detection of known venom peptides from the collected sample using mass spectrometry. The venom collection procedure is followed by a protocol for dissecting spider venom glands, with results demonstrating that this leads to the characterization of venom-expressed proteins and peptides at the sequence level.

  6. Extraction of Venom and Venom Gland Microdissections from Spiders for Proteomic and Transcriptomic Analyses

    PubMed Central

    Garb, Jessica E.

    2014-01-01

    Venoms are chemically complex secretions typically comprising numerous proteins and peptides with varied physiological activities. Functional characterization of venom proteins has important biomedical applications, including the identification of drug leads or probes for cellular receptors. Spiders are the most species rich clade of venomous organisms, but the venoms of only a few species are well-understood, in part due to the difficulty associated with collecting minute quantities of venom from small animals. This paper presents a protocol for the collection of venom from spiders using electrical stimulation, demonstrating the procedure on the Western black widow (Latrodectus hesperus). The collected venom is useful for varied downstream analyses including direct protein identification via mass spectrometry, functional assays, and stimulation of venom gene expression for transcriptomic studies. This technique has the advantage over protocols that isolate venom from whole gland homogenates, which do not separate genuine venom components from cellular proteins that are not secreted as part of the venom. Representative results demonstrate the detection of known venom peptides from the collected sample using mass spectrometry. The venom collection procedure is followed by a protocol for dissecting spider venom glands, with results demonstrating that this leads to the characterization of venom-expressed proteins and peptides at the sequence level. PMID:25407635

  7. Tityus serrulatus venom peptidomics: assessing venom peptide diversity.

    PubMed

    Rates, Breno; Ferraz, Karla K F; Borges, Márcia H; Richardson, Michael; De Lima, Maria Elena; Pimenta, Adriano M C

    2008-10-01

    MALDI-TOF-TOF and de novo sequencing were employed to assess the Tityus serrulatus venom peptide diversity. Previous works has shown the cornucopia of molecular masses, ranging from 800 to 3000Da, present in the venom from this and other scorpions species. This work reports the identification/sequencing of several of these peptides. The majority of the peptides found were fragments of larger venom toxins. For instance, 28 peptides could be identified as fragments from Pape proteins, 10 peptides corresponded to N-terminal fragments of the TsK beta (scorpine-like) toxin and fragments of potassium channel toxins (other than the k-beta) were sequenced as well. N-terminal fragments from the T. serrulatus hypotensins-I and II and a novel hypotensin-like peptide could also be found. This work also reports the sequencing of novel peptides without sequence similarities to other known molecules.

  8. Venom on ice: first insights into Antarctic octopus venoms.

    PubMed

    Undheim, E A B; Georgieva, D N; Thoen, H H; Norman, J A; Mork, J; Betzel, C; Fry, B G

    2010-11-01

    The venom of Antarctic octopus remains completely unstudied. Here, a preliminary investigation was conducted into the properties of posterior salivary gland (PSG) extracts from four Antarctica eledonine (Incirrata; Octopodidae) species (Adelieledone polymorpha, Megaleledone setebos, Pareledone aequipapillae, and Pareledone turqueti) collected from the coast off George V's Land, Antarctica. Specimens were assayed for alkaline phosphatase (ALP), acetylcholinesterase (AChE), proteolytic, phospholipase A(2) (PLA(2)), and haemolytic activities. For comparison, stomach tissue from Cirroctopus sp. (Cirrata; Cirroctopodidae) was also assayed for ALP, AChE, proteolytic and haemolytic activities. Dietary and morphological data were collected from the literature to explore the ecological importance of venom, taking an adaptive evolutionary approach. Of the incirrate species, three showed activities in all assays, while P. turqueti did not exhibit any haemolytic activity. There was evidence for cold-adaptation of ALP in all incirrates, while proteolytic activity in all except P. turqueti. Cirroctopus sp. stomach tissue extract showed ALP, AChE and some proteolytic activity. It was concluded that the AChE activity seen in the PSG extracts was possibly due to a release of household proteins, and not one of the secreted salivary toxins. Although venom undoubtedly plays an important part in prey capture and processing by Antarctica eledonines, no obvious adaptations to differences in diet or morphology were apparent from the enzymatic and haemolytic assays. However, several morphological features including enlarged PSG, small buccal mass, and small beak suggest such adaptations are present. Future studies should be conducted on several levels: Venomic, providing more detailed information on the venom compositions as well as the venom components themselves; ecological, for example application of serological or genetic methods in identifying stomach contents; and behavioural

  9. Ammodytoxin content of Vipera ammodytes ammodytes venom as a prognostic factor for venom immunogenicity.

    PubMed

    Halassy, Beata; Habjanec, Lidija; Balija, Maja Lang; Kurtović, Tihana; Brgles, Marija; Krizaj, Igor

    2010-05-01

    Venoms are complex mixtures of proteins, peptides and other compounds whose biochemical and biological variability has been clearly demonstrated. These molecules have been used as antigens for immunization of anti-venom-producing animals (horses or sheep). Ammodytoxins (Atx) are potently neurotoxic compounds, and the most toxic compounds isolated so far from the Vipera ammodytes ammodytes (Vaa) venom. Recently we have shown that the level of antibodies specific to Vaa venom's most toxic component, ammodytoxin A (AtxA), (anti-AtxA IgG) in Vaa venom immunized rabbit sera highly correlated to the venom toxicity-neutralization potential of these sera. Here we investigated whether Atx content of Vaa venom could influence the outcome of immunization procedure. The novel ELISA was developed for precise determination of Atx content and Atx was quantified in venom samples used for immunization of rabbits. We clearly showed that animals immunized with the venom containing lower amount of Atx produced sera with significantly lower venom toxicity-neutralizing power and, vice versa, animals immunized with venoms containing higher amount of Atx produced sera with higher venom toxicity-neutralizing ability. Thus, the content of Atx in Vaa venom is a relevant parameter of its suitability in the production of highly protective Vaa anti-venom. Copyright 2010 Elsevier Inc. All rights reserved.

  10. Snake venom metalloproteinases.

    PubMed

    Markland, Francis S; Swenson, Stephen

    2013-02-01

    Recent proteomic analyses of snake venoms show that metalloproteinases represent major components in most of the Crotalid and Viperid venoms. In this chapter we discuss the multiple activities of the SVMPs. In addition to hemorrhagic activity, members of the SVMP family also have fibrin(ogen)olytic activity, act as prothrombin activators, activate blood coagulation factor X, possess apoptotic activity, inhibit platelet aggregation, are pro-inflammatory and inactivate blood serine proteinase inhibitors. Clearly the SVMPs have multiple functions in addition to their well-known hemorrhagic activity. The realization that there are structural variations in the SVMPs and the early studies that led to their classification represents an important event in our understanding of the structural forms of the SVMPs. The SVMPs were subdivided into the P-I, P-II and P-III protein classes. The noticeable characteristic that distinguished the different classes was their size (molecular weight) differences and domain structure: Class I (P-I), the small SVMPs, have molecular masses of 20-30 kDa, contain only a pro domain and the proteinase domain; Class II (P-II), the medium size SVMPs, molecular masses of 30-60 kDa, contain the pro domain, proteinase domain and disintegrin domain; Class III (P-III), the large SVMPs, have molecular masses of 60-100 kDa, contain pro, proteinase, disintegrin-like and cysteine-rich domain structure. Another significant advance in the SVMP field was the characterization of the crystal structure of the first P-I class SVMP. The structures of other P-I SVMPs soon followed and the structures of P-III SVMPs have also been determined. The active site of the metalloproteinase domain has a consensus HEXXHXXGXXHD sequence and a Met-turn. The "Met-turn" structure contains a conserved Met residue that forms a hydrophobic basement for the three zinc-binding histidines in the consensus sequence. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Venom gland transcriptomics for identifying, cataloging, and characterizing venom proteins in snakes.

    PubMed

    Brahma, Rajeev Kungur; McCleary, Ryan J R; Kini, R Manjunatha; Doley, Robin

    2015-01-01

    Snake venoms are cocktails of protein toxins that play important roles in capture and digestion of prey. Significant qualitative and quantitative variation in snake venom composition has been observed among and within species. Understanding these variations in protein components is instrumental in interpreting clinical symptoms during human envenomation and in searching for novel venom proteins with potential therapeutic applications. In the last decade, transcriptomic analyses of venom glands have helped in understanding the composition of various snake venoms in great detail. Here we review transcriptomic analysis as a powerful tool for understanding venom profile, variation and evolution.

  12. Hymenoptera venom allergy in humans.

    PubMed

    Cichocka-Jarosz, Ewa

    2012-01-01

    Reactions to Hymenoptera stings may appear as local or systemic responses. According to European data, the incidence of systemic reactions to Hymenoptera stings in the general population is 0.3-7.5%, with the value being 0.3-0.8% in children and 14-43% in beekeepers. The most common systemic allergic (anaphylactic) reactions are caused by honeybees (Apis mellifera), and certain species of wasps in the family Vespidae. Severe generalized immediate-type allergic (anaphylactic) reactions to insect stings are of the highest clinical importance. They affect skin, gastrointestinal tract, respiratory and cardiovascular system. The classification of severity of anaphylactic reaction following insect stings is based on the 4-grade Mueller scale. Crucial in patomechanism of anaphylaxis are specific IgE antibodies directed against the components of the venom, which mediate the activation of mast cells, the main effector cells of anaphylaxis. Therapeutic management in insect venom allergy should be considered in the context of prophylaxis, intervention in case symptoms develop, prevention in the form of venom specific immunotherapy (VIT). There are two steps of VIT 1. Initial dose venom immunotherapy (given according to four protocols which differ the time to reach the maintenance dose) 2. Maintenance dose VIT, usually equal 100 µg. Standard treatment time should span 3-5 years. The main mechanisms of immune tolerance that are initiated by VIT are associated with: 1. a decreased reactivity of effector cells, 2. expansion of T regulatory lymphocytes with IL-10 expression. Therapeutic effectiveness amounts to 90-100% in wasp venom allergy and approximately 80% in bee venom allergy.

  13. [Study on the venoms of the principal venomous snakes from French Guiana and the neutralization].

    PubMed

    Estévez, J; Magaña, P; Chippaux, J P; Vidal, N; Mancilla, R; Paniagua, J F; de Roodt, A R

    2008-10-01

    We studied some biochemical, toxic and immunological characteristics of the venoms of Bothrops atrox, Bothrops brazili and Lachesis muta, Viperidae responsible for most of the bites of venomous snakes in French Guiana. Chromatographic (HPLC) and electrophoretical profiles (SDS-PAGE), lethal, hemorrhagic, defibrinogenating, coagulant, thrombin like, proteolytic, fibrino(geno)lytic and phospholipase activities were studied. In addition, the neutralization of some toxic activities conferred by four antivenins was compared. The chromatographic and electrophoretic profiles were different for the three venoms, showing differences between Bothrops and L. muta venoms. In general, bothropic venoms showed the highest toxic and enzymatic activities, while the venom of L. muta showed the lowest lethal, hemorrhagic and coagulant activities. The enzymes of bothropic venoms responsible for gelatinolytic activity were around 50-90 kDa. All the venoms were able to hydrolyze a and beta chains of the fibrinogen, showing different patterns of degradation. Although all the antivenoms tested were effective to various degrees in neutralizing the venom of B. brazili and B. atrox, neutralization of L. muta venom was significantly better achieved using the antivenom including this venom in its immunogenic mixture. For the neutralization of L. muta venom, homologous or polyvalent antivenoms that include the "bushmaster" venom in their immunogenic mixture should be preferred.

  14. Toxicity of crude and detoxified Tityus serrulatus venom in anti-venom-producing sheep

    PubMed Central

    Ferreira, Marina G.; Duarte, Clara G.; Oliveira, Maira S.; Castro, Karen L. P.; Teixeira, Maílson S.; Reis, Lílian P. G.; Zambrano, José A.; Kalapothakis, Evanguedes; Michel, Ana Flávia R. M.; Soto-Blanco, Benito; Chávez-Olórtegui, Carlos

    2016-01-01

    Specific anti-venom used to treat scorpion envenomation is usually obtained from horses after hyperimmunization with crude scorpion venom. However, immunized animals often become ill because of the toxic effects of the immunogens used. This study was conducted to evaluate the toxic and immunogenic activities of crude and detoxified Tityus serrulatus (Ts) venom in sheep during the production of anti-scorpionic anti-venom. Sheep were categorized into three groups: G1, control, immunized with buffer only; G2, immunized with crude Ts venom; and G3, immunized with glutaraldehyde-detoxified Ts venom. All animals were subjected to clinical exams and supplementary tests. G2 sheep showed mild clinical changes, but the other groups tolerated the immunization program well. Specific antibodies generated in animals immunized with either Ts crude venom or glutaraldehyde-detoxified Ts venom recognized the crude Ts venom in both assays. To evaluate the lethality neutralization potential of the produced sera, individual serum samples were pre-incubated with Ts crude venom, then subcutaneously injected into mice. Efficient immune protection of 56.3% and 43.8% against Ts crude venom was observed in G2 and G3, respectively. Overall, the results of this study support the use of sheep and glutaraldehyde-detoxified Ts venom for alternative production of specific anti-venom. PMID:27297422

  15. Toxicity of crude and detoxified Tityus serrulatus venom in anti-venom-producing sheep.

    PubMed

    Ferreira, Marina G; Duarte, Clara G; Oliveira, Maira S; Castro, Karen L P; Teixeira, Maílson S; Reis, Lílian P G; Zambrano, José A; Kalapothakis, Evanguedes; Michel, Ana Flávia R M; Soto-Blanco, Benito; Chávez-Olórtegui, Carlos; Melo, Marília M

    2016-12-30

    Specific anti-venom used to treat scorpion envenomation is usually obtained from horses after hyperimmunization with crude scorpion venom. However, immunized animals often become ill because of the toxic effects of the immunogens used. This study was conducted to evaluate the toxic and immunogenic activities of crude and detoxified Tityus serrulatus (Ts) venom in sheep during the production of anti-scorpionic anti-venom. Sheep were categorized into three groups: G1, control, immunized with buffer only; G2, immunized with crude Ts venom; and G3, immunized with glutaraldehyde-detoxified Ts venom. All animals were subjected to clinical exams and supplementary tests. G2 sheep showed mild clinical changes, but the other groups tolerated the immunization program well. Specific antibodies generated in animals immunized with either Ts crude venom or glutaraldehyde-detoxified Ts venom recognized the crude Ts venom in both assays. To evaluate the lethality neutralization potential of the produced sera, individual serum samples were pre-incubated with Ts crude venom, then subcutaneously injected into mice. Efficient immune protection of 56.3% and 43.8% against Ts crude venom was observed in G2 and G3, respectively. Overall, the results of this study support the use of sheep and glutaraldehyde-detoxified Ts venom for alternative production of specific anti-venom.

  16. DISC ELECTROPHORESIS OF HYMENOPTERA VENOMS AND BODY PROTEINS.

    PubMed

    O'CONNOR, R; ROSENBROOK, W; ERICKSON, R

    1964-09-18

    The venom proteins of honey bee, Polistes wasp, yellow hornet, and yellow jacket are similar but not identical. Extracts of venom sacs and whole insects contain several proteins not found in the pure venoms.

  17. A Polychaete’s Powerful Punch: Venom Gland Transcriptomics of Glycera Reveals a Complex Cocktail of Toxin Homologs

    PubMed Central

    von Reumont, Björn M.; Richter, Sandy; Hering, Lars; Sykes, Dan; Hetmank, Jörg; Jenner, Ronald A.; Bleidorn, Christoph

    2014-01-01

    Glycerids are marine annelids commonly known as bloodworms. Bloodworms have an eversible proboscis adorned with jaws connected to venom glands. Bloodworms prey on invertebrates, and it is known that the venom glands produce compounds that can induce toxic effects in animals. Yet, none of these putative toxins has been characterized on a molecular basis. Here we present the transcriptomic profiles of the venom glands of three species of bloodworm, Glycera dibranchiata, Glycera fallax and Glycera tridactyla, as well as the body tissue of G. tridactyla. The venom glands express a complex mixture of transcripts coding for putative toxin precursors. These transcripts represent 20 known toxin classes that have been convergently recruited into animal venoms, as well as transcripts potentially coding for Glycera-specific toxins. The toxins represent five functional categories: Pore-forming and membrane-disrupting toxins, neurotoxins, protease inhibitors, other enzymes, and CAP domain toxins. Many of the transcripts coding for putative Glycera toxins belong to classes that have been widely recruited into venoms, but some are homologs of toxins previously only known from the venoms of scorpaeniform fish and monotremes (stonustoxin-like toxin), turrid gastropods (turripeptide-like peptides), and sea anemones (gigantoxin I-like neurotoxin). This complex mixture of toxin homologs suggests that bloodworms employ venom while predating on macroscopic prey, casting doubt on the previously widespread opinion that G. dibranchiata is a detritivore. Our results further show that researchers should be aware that different assembly methods, as well as different methods of homology prediction, can influence the transcriptomic profiling of venom glands. PMID:25193302

  18. Colubrid Venom Composition: An -Omics Perspective

    PubMed Central

    Junqueira-de-Azevedo, Inácio L. M.; Campos, Pollyanna F.; Ching, Ana T. C.; Mackessy, Stephen P.

    2016-01-01

    Snake venoms have been subjected to increasingly sensitive analyses for well over 100 years, but most research has been restricted to front-fanged snakes, which actually represent a relatively small proportion of extant species of advanced snakes. Because rear-fanged snakes are a diverse and distinct radiation of the advanced snakes, understanding venom composition among “colubrids” is critical to understanding the evolution of venom among snakes. Here we review the state of knowledge concerning rear-fanged snake venom composition, emphasizing those toxins for which protein or transcript sequences are available. We have also added new transcriptome-based data on venoms of three species of rear-fanged snakes. Based on this compilation, it is apparent that several components, including cysteine-rich secretory proteins (CRiSPs), C-type lectins (CTLs), CTLs-like proteins and snake venom metalloproteinases (SVMPs), are broadly distributed among “colubrid” venoms, while others, notably three-finger toxins (3FTxs), appear nearly restricted to the Colubridae (sensu stricto). Some putative new toxins, such as snake venom matrix metalloproteinases, are in fact present in several colubrid venoms, while others are only transcribed, at lower levels. This work provides insights into the evolution of these toxin classes, but because only a small number of species have been explored, generalizations are still rather limited. It is likely that new venom protein families await discovery, particularly among those species with highly specialized diets. PMID:27455326

  19. Colubrid Venom Composition: An -Omics Perspective.

    PubMed

    Junqueira-de-Azevedo, Inácio L M; Campos, Pollyanna F; Ching, Ana T C; Mackessy, Stephen P

    2016-07-23

    Snake venoms have been subjected to increasingly sensitive analyses for well over 100 years, but most research has been restricted to front-fanged snakes, which actually represent a relatively small proportion of extant species of advanced snakes. Because rear-fanged snakes are a diverse and distinct radiation of the advanced snakes, understanding venom composition among "colubrids" is critical to understanding the evolution of venom among snakes. Here we review the state of knowledge concerning rear-fanged snake venom composition, emphasizing those toxins for which protein or transcript sequences are available. We have also added new transcriptome-based data on venoms of three species of rear-fanged snakes. Based on this compilation, it is apparent that several components, including cysteine-rich secretory proteins (CRiSPs), C-type lectins (CTLs), CTLs-like proteins and snake venom metalloproteinases (SVMPs), are broadly distributed among "colubrid" venoms, while others, notably three-finger toxins (3FTxs), appear nearly restricted to the Colubridae (sensu stricto). Some putative new toxins, such as snake venom matrix metalloproteinases, are in fact present in several colubrid venoms, while others are only transcribed, at lower levels. This work provides insights into the evolution of these toxin classes, but because only a small number of species have been explored, generalizations are still rather limited. It is likely that new venom protein families await discovery, particularly among those species with highly specialized diets.

  20. Venom Insulins of Cone Snails Diversify Rapidly and Track Prey Taxa.

    PubMed

    Safavi-Hemami, Helena; Lu, Aiping; Li, Qing; Fedosov, Alexander E; Biggs, Jason; Showers Corneli, Patrice; Seger, Jon; Yandell, Mark; Olivera, Baldomero M

    2016-11-01

    A specialized insulin was recently found in the venom of a fish-hunting cone snail, Conus geographus Here we show that many worm-hunting and snail-hunting cones also express venom insulins, and that this novel gene family has diversified explosively. Cone snails express a highly conserved insulin in their nerve ring; presumably this conventional signaling insulin is finely tuned to the Conus insulin receptor, which also evolves very slowly. By contrast, the venom insulins diverge rapidly, apparently in response to biotic interactions with prey and also possibly the cones' own predators and competitors. Thus, the inwardly directed signaling insulins appear to experience predominantly purifying sele\\ction to target an internal receptor that seldom changes, while the outwardly directed venom insulins frequently experience directional selection to target heterospecific insulin receptors in a changing mix of prey, predators and competitors. Prey insulin receptors may often be constrained in ways that prevent their evolutionary escape from targeted venom insulins, if amino-acid substitutions that result in escape also degrade the receptor's signaling functions. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. Venom Insulins of Cone Snails Diversify Rapidly and Track Prey Taxa

    PubMed Central

    Safavi-Hemami, Helena; Lu, Aiping; Li, Qing; Fedosov, Alexander E.; Biggs, Jason; Showers Corneli, Patrice; Seger, Jon; Yandell, Mark; Olivera, Baldomero M.

    2016-01-01

    A specialized insulin was recently found in the venom of a fish-hunting cone snail, Conus geographus. Here we show that many worm-hunting and snail-hunting cones also express venom insulins, and that this novel gene family has diversified explosively. Cone snails express a highly conserved insulin in their nerve ring; presumably this conventional signaling insulin is finely tuned to the Conus insulin receptor, which also evolves very slowly. By contrast, the venom insulins diverge rapidly, apparently in response to biotic interactions with prey and also possibly the cones’ own predators and competitors. Thus, the inwardly directed signaling insulins appear to experience predominantly purifying sele\\ction to target an internal receptor that seldom changes, while the outwardly directed venom insulins frequently experience directional selection to target heterospecific insulin receptors in a changing mix of prey, predators and competitors. Prey insulin receptors may often be constrained in ways that prevent their evolutionary escape from targeted venom insulins, if amino-acid substitutions that result in escape also degrade the receptor’s signaling functions. PMID:27524826

  2. Biodiversity of cone snails and other venomous marine gastropods: evolutionary success through neuropharmacology.

    PubMed

    Olivera, Baldomero M; Showers Corneli, Patrice; Watkins, Maren; Fedosov, Alexander

    2014-02-01

    Venomous marine snails (superfamily Conoidea) are a remarkably biodiverse marine invertebrate lineage (featuring more than 10,000 species). Conoideans use complex venoms (up to 100 different components for each species) to capture prey and for other biotic interactions. Molecular phylogeny and venom peptide characterization provide an unusual multidisciplinary view of conoidean biodiversity at several taxonomic levels. Venom peptides diverge between species at an unprecedented rate through hypermutation within gene families. Clade divergence within a genus occurs without recruiting new gene families when a saltatory event, such as colonization of new prey types (e.g., fish), leads to a new radiation. Divergence between genera in the same family involves substantial divergence in gene families. In the superfamily Conoidea, the family groups recruited distinct sets of different venom gene superfamilies. The associated morphological, behavioral, and prey-preference changes that accompany these molecular changes are unknown for most conoidean lineages, except for one genus, Conus, for which many associated phenotypic changes have been documented.

  3. Venom gland transcriptome analyses of two freshwater stingrays (Myliobatiformes: Potamotrygonidae) from Brazil.

    PubMed

    de Oliveira Júnior, Nelson Gomes; Fernandes, Gabriel da Rocha; Cardoso, Marlon Henrique; Costa, Fabrício F; Cândido, Elizabete de Souza; Garrone Neto, Domingos; Mortari, Márcia Renata; Schwartz, Elisabeth Ferroni; Franco, Octávio Luiz; de Alencar, Sérgio Amorim

    2016-02-26

    Stingrays commonly cause human envenoming related accidents in populations of the sea, near rivers and lakes. Transcriptomic profiles have been used to elucidate components of animal venom, since they are capable of providing molecular information on the biology of the animal and could have biomedical applications. In this study, we elucidated the transcriptomic profile of the venom glands from two different freshwater stingray species that are endemic to the Paraná-Paraguay basin in Brazil, Potamotrygon amandae and Potamotrygon falkneri. Using RNA-Seq, we identified species-specific transcripts and overlapping proteins in the venom gland of both species. Among the transcripts related with envenoming, high abundance of hyaluronidases was observed in both species. In addition, we built three-dimensional homology models based on several venom transcripts identified. Our study represents a significant improvement in the information about the venoms employed by these two species and their molecular characteristics. Moreover, the information generated by our group helps in a better understanding of the biology of freshwater cartilaginous fishes and offers clues for the development of clinical treatments for stingray envenoming in Brazil and around the world. Finally, our results might have biomedical implications in developing treatments for complex diseases.

  4. Venom gland transcriptome analyses of two freshwater stingrays (Myliobatiformes: Potamotrygonidae) from Brazil

    PubMed Central

    Júnior, Nelson Gomes de Oliveira; Fernandes, Gabriel da Rocha; Cardoso, Marlon Henrique; Costa, Fabrício F.; Cândido, Elizabete de Souza; Neto, Domingos Garrone; Mortari, Márcia Renata; Schwartz, Elisabeth Ferroni; Franco, Octávio Luiz; de Alencar, Sérgio Amorim

    2016-01-01

    Stingrays commonly cause human envenoming related accidents in populations of the sea, near rivers and lakes. Transcriptomic profiles have been used to elucidate components of animal venom, since they are capable of providing molecular information on the biology of the animal and could have biomedical applications. In this study, we elucidated the transcriptomic profile of the venom glands from two different freshwater stingray species that are endemic to the Paraná-Paraguay basin in Brazil, Potamotrygon amandae and Potamotrygon falkneri. Using RNA-Seq, we identified species-specific transcripts and overlapping proteins in the venom gland of both species. Among the transcripts related with envenoming, high abundance of hyaluronidases was observed in both species. In addition, we built three-dimensional homology models based on several venom transcripts identified. Our study represents a significant improvement in the information about the venoms employed by these two species and their molecular characteristics. Moreover, the information generated by our group helps in a better understanding of the biology of freshwater cartilaginous fishes and offers clues for the development of clinical treatments for stingray envenoming in Brazil and around the world. Finally, our results might have biomedical implications in developing treatments for complex diseases. PMID:26916342

  5. [The threat of snake and scorpion venoms].

    PubMed

    Płusa, Tadeusz; Smędzik, Katarzyna

    2015-09-01

    Venoms of snakes and scorpions pose a significant threat to the health and life of humans. The speed and range of their actions causes damage of the organ responsible for the maintenance of vital signs. Venomous snake venoms cause blood clotting disorders, tissue necrosis and hemolysis, and the release of a number of proinflammatory cytokines and impair antibody synthesis. Availability of antitoxins is limited and in the most cases supportive treatment is recommended. In turn, the venom of scorpions beside intestinal symptoms cause significant impairment of neuromuscular conduction, causing severe respiratory disorders. Action venom poses a particular threat to sensitive patients. The degree of threat to life caused by the venom of snakes and scorpions authorizes the treatment of these substances as a potential biological weapon.

  6. Species identification from dried snake venom.

    PubMed

    Singh, Chandra S; Gaur, Ajay; Sreenivas, Ara; Singh, Lalji

    2012-05-01

    Illegal trade in snake parts has increased enormously. In spite of strict protection under wildlife act, a large number of snakes are being killed ruthlessly in India for venom and skin. Here, an interesting case involving confiscation of crystallized dried snake venom and subsequent DNA-based species identification is reported. The analysis using the universal primers for cytochrome b region of the mitochondrial DNA revealed that the venom was extracted from an Indian cobra (Naja naja). On the basis of this report, the forwarding authority booked a case in the court of law against the accused for illegal hunting of an endangered venomous snake and smuggling of snake venom. This approach thus has immense potential for rapid identification of snake species facing endangerment because of illegal trade. This is also the first report of DNA isolation from dried snake venom for species identification.

  7. Specialized insulin is used for chemical warfare by fish-hunting cone snails.

    PubMed

    Safavi-Hemami, Helena; Gajewiak, Joanna; Karanth, Santhosh; Robinson, Samuel D; Ueberheide, Beatrix; Douglass, Adam D; Schlegel, Amnon; Imperial, Julita S; Watkins, Maren; Bandyopadhyay, Pradip K; Yandell, Mark; Li, Qing; Purcell, Anthony W; Norton, Raymond S; Ellgaard, Lars; Olivera, Baldomero M

    2015-02-10

    More than 100 species of venomous cone snails (genus Conus) are highly effective predators of fish. The vast majority of venom components identified and functionally characterized to date are neurotoxins specifically targeted to receptors, ion channels, and transporters in the nervous system of prey, predators, or competitors. Here we describe a venom component targeting energy metabolism, a radically different mechanism. Two fish-hunting cone snails, Conus geographus and Conus tulipa, have evolved specialized insulins that are expressed as major components of their venoms. These insulins are distinctive in having much greater similarity to fish insulins than to the molluscan hormone and are unique in that posttranslational modifications characteristic of conotoxins (hydroxyproline, γ-carboxyglutamate) are present. When injected into fish, the venom insulin elicits hypoglycemic shock, a condition characterized by dangerously low blood glucose. Our evidence suggests that insulin is specifically used as a weapon for prey capture by a subset of fish-hunting cone snails that use a net strategy to capture prey. Insulin appears to be a component of the nirvana cabal, a toxin combination in these venoms that is released into the water to disorient schools of small fish, making them easier to engulf with the snail's distended false mouth, which functions as a net. If an entire school of fish simultaneously experiences hypoglycemic shock, this should directly facilitate capture by the predatory snail.

  8. Exploring the therapeutic potential of jellyfish venom.

    PubMed

    Daly, Norelle L; Seymour, Jamie; Wilson, David

    2014-10-01

    The venom of certain jellyfish has long been known to be potentially fatal to humans, but it is only recently that details of the proteomes of these fascinating creatures are emerging. The molecular contents of the nematocysts from several jellyfish species have now been analyzed using proteomic MS approaches and include the analysis of Chironex fleckeri, one of the most venomous jellyfish known. These studies suggest that some species contain toxins related to peptides and proteins found in other venomous creatures. The detailed characterization of jellyfish venom is likely to provide insight into the diversification of toxins and might be a valuable resource in drug design.

  9. Snake venom toxins: toxicity and medicinal applications.

    PubMed

    Chan, Yau Sang; Cheung, Randy Chi Fai; Xia, Lixin; Wong, Jack Ho; Ng, Tzi Bun; Chan, Wai Yee

    2016-07-01

    Snake venoms are complex mixtures of small molecules and peptides/proteins, and most of them display certain kinds of bioactivities. They include neurotoxic, cytotoxic, cardiotoxic, myotoxic, and many different enzymatic activities. Snake envenomation is a significant health issue as millions of snakebites are reported annually. A large number of people are injured and die due to snake venom poisoning. However, several fatal snake venom toxins have found potential uses as diagnostic tools, therapeutic agent, or drug leads. In this review, different non-enzymatically active snake venom toxins which have potential therapeutic properties such as antitumor, antimicrobial, anticoagulating, and analgesic activities will be discussed.

  10. The Biochemical Toxin Arsenal from Ant Venoms.

    PubMed

    Touchard, Axel; Aili, Samira R; Fox, Eduardo Gonçalves Paterson; Escoubas, Pierre; Orivel, Jérôme; Nicholson, Graham M; Dejean, Alain

    2016-01-20

    Ants (Formicidae) represent a taxonomically diverse group of hymenopterans with over 13,000 extant species, the majority of which inject or spray secretions from a venom gland. The evolutionary success of ants is mostly due to their unique eusociality that has permitted them to develop complex collaborative strategies, partly involving their venom secretions, to defend their nest against predators, microbial pathogens, ant competitors, and to hunt prey. Activities of ant venom include paralytic, cytolytic, haemolytic, allergenic, pro-inflammatory, insecticidal, antimicrobial, and pain-producing pharmacologic activities, while non-toxic functions include roles in chemical communication involving trail and sex pheromones, deterrents, and aggregators. While these diverse activities in ant venoms have until now been largely understudied due to the small venom yield from ants, modern analytical and venomic techniques are beginning to reveal the diversity of toxin structure and function. As such, ant venoms are distinct from other venomous animals, not only rich in linear, dimeric and disulfide-bonded peptides and bioactive proteins, but also other volatile and non-volatile compounds such as alkaloids and hydrocarbons. The present review details the unique structures and pharmacologies of known ant venom proteinaceous and alkaloidal toxins and their potential as a source of novel bioinsecticides and therapeutic agents.

  11. Hydrolysis of DNA by 17 snake venoms.

    PubMed

    de Roodt, Adolfo Rafael; Litwin, Silvana; Angel, Sergio O

    2003-08-01

    DNA hydrolysis caused by venoms of 17 species of snakes was studied by different methodologies. Endonucleolytic activity was tested by incubation of the venoms with the plasmid pBluescript and subsequent visualization of the electrophoretic patterns in 1% agarose gels stained with ethidium bromide. DNA was sequentially degraded, from supercoiled to opened circle, to linear form, in a concentration dependent manner. The highest hydrolytic activity was observed in Bothrops (B.) neuwiedii and Naja (N.) siamensis venoms. Exonucleolytic activity was analyzed on pBluescript digested with SmaI or EcoRI. All venoms caused complete hydrolysis after 2 h of incubation. SDS-PAGE analysis in gels containing calf thymus DNA showed that the hydrolytic bands were located at approximately 30 kDa. DNA degradation was studied by radial hydrolysis in 1% agarose gels containing calf thymus DNA plus ethidium bromide and visualized by UV light. Venom of B. neuwiedii showed the highest activity whereas those of B. ammodytoides and Ovophis okinavensis (P<0.05) showed the lowest activity. Antibodies against venom of B. neuwiedii or N. siamensis neutralized the DNAse activity of both venoms. In conclusion, venom from different snakes showed endo- and exonucleolytic activity on DNA. The inhibition of DNA hydrolysis by EDTA and heterologous antibodies suggests similarities in the structure of the venom components involved.

  12. The Biochemical Toxin Arsenal from Ant Venoms

    PubMed Central

    Touchard, Axel; Aili, Samira R.; Fox, Eduardo Gonçalves Paterson; Escoubas, Pierre; Orivel, Jérôme; Nicholson, Graham M.; Dejean, Alain

    2016-01-01

    Ants (Formicidae) represent a taxonomically diverse group of hymenopterans with over 13,000 extant species, the majority of which inject or spray secretions from a venom gland. The evolutionary success of ants is mostly due to their unique eusociality that has permitted them to develop complex collaborative strategies, partly involving their venom secretions, to defend their nest against predators, microbial pathogens, ant competitors, and to hunt prey. Activities of ant venom include paralytic, cytolytic, haemolytic, allergenic, pro-inflammatory, insecticidal, antimicrobial, and pain-producing pharmacologic activities, while non-toxic functions include roles in chemical communication involving trail and sex pheromones, deterrents, and aggregators. While these diverse activities in ant venoms have until now been largely understudied due to the small venom yield from ants, modern analytical and venomic techniques are beginning to reveal the diversity of toxin structure and function. As such, ant venoms are distinct from other venomous animals, not only rich in linear, dimeric and disulfide-bonded peptides and bioactive proteins, but also other volatile and non-volatile compounds such as alkaloids and hydrocarbons. The present review details the unique structures and pharmacologies of known ant venom proteinaceous and alkaloidal toxins and their potential as a source of novel bioinsecticides and therapeutic agents. PMID:26805882

  13. Peptide Toxins in Solitary Wasp Venoms

    PubMed Central

    Konno, Katsuhiro; Kazuma, Kohei; Nihei, Ken-ichi

    2016-01-01

    Solitary wasps paralyze insects or spiders with stinging venom and feed the paralyzed preys to their larva. Accordingly, the venoms should contain a variety of constituents acting on nervous systems. However, only a few solitary wasp venoms have been chemically studied despite thousands of species inhabiting the planet. We have surveyed bioactive substances in solitary wasp venoms found in Japan and discovered a variety of novel bioactive peptides. Pompilidotoxins (PMTXs), in the venoms of the pompilid wasps Anoplius samariensis and Batozonellus maculifrons, are small peptides consisting of 13 amino acids without a disulfide bond. PMTXs slowed Na+ channel inactivation, in particular against neuronal type Na+ channels, and were rather selective to the Nav1.6 channel. Mastoparan-like cytolytic and antimicrobial peptides are the major components of eumenine wasp venoms. They are rich in hydrophobic and basic amino acids, adopting a α-helical secondary structure, and showing mast cell degranulating, antimicrobial and hemolytic activities. The venom of the spider wasp Cyphononyx fulvognathus contained four bradykinin-related peptides. They are hyperalgesic and, dependent on the structure, differently associated with B1 or B2 receptors. Further survey led to the isolation of leucomyosuppressin-like FMRFamide peptides from the venoms of the digger wasps Sphex argentatus and Isodontia harmandi. These results of peptide toxins in solitary wasp venoms from our studies are summarized. PMID:27096870

  14. Venom regeneration in the centipede Scolopendra polymorpha: evidence for asynchronous venom component synthesis.

    PubMed

    Cooper, Allen M; Kelln, Wayne J; Hayes, William K

    2014-12-01

    Venom regeneration comprises a vital process in animals that rely on venom for prey capture and defense. Venom regeneration in scolopendromorph centipedes likely influences their ability to subdue prey and defend themselves, and may influence the quantity and quality of venom extracted by researchers investigating the venom's biochemistry. We investigated venom volume and total protein regeneration during the 14-day period subsequent to venom extraction in the North American centipede Scolopendra polymorpha. We further tested the hypothesis that venom protein components, separated by reversed-phase fast protein liquid chromatography (RP-FPLC), undergo asynchronous (non-parallel) synthesis. During the first 48 h, volume and protein mass increased linearly. Protein regeneration lagged behind volume regeneration, with 65–86% of venom volume and 29–47% of protein mass regenerated during the first 2 days. No additional regeneration occurred over the subsequent 12 days, and neither volume nor protein mass reached initial levels 7 months later (93% and 76%, respectively). Centipede body length was negatively associated with rate of venom regeneration. Analysis of chromatograms of individual venom samples revealed that 5 of 10 chromatographic regions and 12 of 28 peaks demonstrated changes in percent of total peak area (i.e., percent of total protein) among milking intervals, indicating that venom proteins are regenerated asynchronously. Moreover, specimens from Arizona and California differed in relative amounts of some venom components. The considerable regeneration of venom occurring within the first 48 h, despite the reduced protein content, suggests that predatory and defensive capacities are minimally constrained by the timing of venom replacement.

  15. A new approach for investigating venom function applied to venom calreticulin in a parasitoid wasp

    PubMed Central

    Siebert, Aisha L.; Wheeler, David; Werren, John H.

    2015-01-01

    A new method is developed to investigate functions of venom components, using venom gene RNA interference knockdown in the venomous animal coupled with RNA sequencing in the envenomated host animal. The vRNAi/eRNA-Seq approach is applied to the venom calreticulin component (v-crc) of the parasitoid wasp Nasonia vitripennis. Parasitoids are common, venomous animals that inject venom proteins into host insects, where they modulate physiology and metabolism to produce a better food resource for the parasitoid larvae. vRNAi/eRNA-Seq indicates that v-crc acts to suppress expression of innate immune cell response, enhance expression of clotting genes in the host, and up-regulate cuticle genes. V-crc KD also results in an increased melanization reaction immediately following envenomation. We propose that v-crc inhibits innate immune response to parasitoid venom and reduces host bleeding during adult and larval parasitoid feeding. Experiments do not support the hypothesis that v-crc is required for the developmental arrest phenotype observed in envenomated hosts. We propose that an important role for some venom components is to reduce (modulate) the exaggerated effects of other venom components on target host gene expression, physiology, and survival, and term this venom mitigation. A model is developed that uses vRNAi/eRNA-Seq to quantify the contribution of individual venom components to total venom phenotypes, and to define different categories of mitigation by individual venoms on host gene expression. Mitigating functions likely contribute to the diversity of venom proteins in parasitoids and other venomous organisms. PMID:26359852

  16. Venom immunotherapy in patients with mastocytosis and hymenoptera venom anaphylaxis.

    PubMed

    González-de-Olano, David; Alvarez-Twose, Iván; Vega, Arantza; Orfao, Alberto; Escribano, Luis

    2011-05-01

    Systemic mastocytosis (SM) is typically suspected in patients with cutaneous mastocytosis (CM). In recent years, the presence of clonal mast cells (MCs) in a subset of patients with systemic symptoms associated with MC activation in the absence of CM has been reported and termed monoclonal MC activation syndromes or clonal systemic MC activation syndromes. In these cases, bone marrow (BM) MC numbers are usually lower than in SM with CM, there are no detectable BM MC aggregates, and serum baseline tryptase is often <20 µg/l; thus, diagnosis of SM in these patients should be based on careful evaluation of other minor WHO criteria for SM in reference centers, where highly sensitive techniques for immunophenotypic analysis and investigation of KIT mutations on fluorescence-activated cell sorter-purified BM MCs are routinely performed. The prevalence of hymenoptera venom anaphylaxis (HVA) among SM patients is higher than among the normal population and it has been reported to be approximately 5%. In SM patients with IgE-mediated HVA, venom immunotherapy is safe and effective and it should be prescribed lifelong. Severe adverse reactions to hymenoptera stings or venom immunotherapy have been associated with increased serum baseline tryptase; however, presence of clonal MC has not been ruled out in most reports and thus both SM and clonal MC activation syndrome might be underdiagnosed in such patients. In fact, clonal BM MC appears to be a relevant risk factor for both HVA and severe reactions to venom immunotherapy, while the increase in serum baseline tryptase by itself should be considered as a powerful surrogate marker for anaphylaxis. The Spanish Network on Mastocytosis has developed a scoring system based on patient gender, the clinical symptoms observed during anaphylaxis and serum baseline tryptase to predict for the presence of both MC clonality and SM among individuals who suffer from anaphylaxis.

  17. Description of histopathological changes induced by the venom of the Persian Gulf Lionfish (Pterois russelli) in a mouse model of multiorgan toxicity.

    PubMed

    Memar, Bahareh; Jamili, Shahla; Shahbazzadeh, Delavar; Pooshang Bagheri, Kamran

    2016-11-01

    Pterois russelli is a venomous fish belongs to Scorpaenidae family. Envenomation by the Persian Gulf lionfish is associated with local pain, marked inflammation and local heat. The present study was aimed to document the histopathological changes in liver, heart, lung, kidney and alterations in release of critical enzymes such as LDH, CK. AST, ALT and ALP induced by the administration of various doses of P. russelli venom in a mouse model. LD50 of venom was determined by intravenous injection in Balb/c mice. Histopathological alterations of lung, liver, heart and kidney following injection of one LD50, 1/2 and 1/3 LD50 doses of the venom were evaluated. Simultaneously, release of LDH, CK, AST, ALT and ALP were measured in serum following administration of 1/2 and1/3 LD50 doses of the venom too. LD50 was calculated as 10.5 mg/kg. The level of all enzymes were increased after 3 h and significantly raised after 24 h and rapidly reduced after 48 h. Histological studies showed that one LD50 and 1/2 LD50 doses of the venom induced significant histological alterations in the lungs, liver, heart and kidneys including congestion, hemorrhage, necrosis, apoptosis, edema, and infiltration of inflammatory cells. The results indicate that the venom of P. russelli has nephrotoxic, hepatotoxic, cardiotoxic and pneumotoxic effects in mouse model. Among four examined vital organs, the highest critical events were seen in liver. The findings are useful to give new insight in the fish's venom studies. Gathering the data resulted from this study together will be directed us toward a good aspect concerning the toxicity of potential therapeutic molecules in the venom of lionfish. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Pharmacological action of Australian animal venoms.

    PubMed

    Hodgson, W C

    1997-01-01

    1. Australia has some of the most venomous fauna in the world. Although humans are not usually perceived as being predators against these animals they are often envenomated, accidentally or otherwise. This has led to the development of antivenoms against some of the potentially lethal venoms. However, further understanding of the mechanism(s) of action of these and other venoms is important, not only for developing new treatment strategies but also in the search for novel research tools. 2. The present review discusses the pharmacology of some of the components found in venoms and outlines the research undertaken on some of Australia's venomous animals, with the exception of snakes. 3. Biogenic amines, peptides and enzymes are common venom components and produce a wide range of effects in envenomated humans. For example, respiratory failure observed after envenomation by the box jellyfish (Chirnex fleckeri) and Sydney funnel-web spider (Atrax robustus) is most likely due to potent neurotoxins in the venoms. Stonefish (Synanceja trachynis) and platypus (Ornithorhynchus anatinus) venoms, although not considered lethal, cause severe pain. However, the components responsible for these effects have not been isolated. Venom components, as yet unidentified, may be responsible for the cutaneous necrotic lesions that have been reported after some spider bites (e.g. Lampona cylindrata). Other venoms, such as those of the jumper ant (Myrmecia pilosula) and bull ant (M. pyriformis), may produce only mild skin irritation to the majority of humans but a severe anaphylactic response in sensitized victims. 4. While there has been a renewed interest in toxinology, further research is required to fully elucidate the pharmacological action of many of these venoms.

  19. Snake venomics and venom gland transcriptomic analysis of Brazilian coral snakes, Micrurus altirostris and M. corallinus.

    PubMed

    Corrêa-Netto, Carlos; Junqueira-de-Azevedo, Inácio de L M; Silva, Débora A; Ho, Paulo L; Leitão-de-Araújo, Moema; Alves, Maria Lúcia M; Sanz, Libia; Foguel, Débora; Zingali, Russolina Benedeta; Calvete, Juan J

    2011-08-24

    The venom proteomes of Micrurus altirostris and M. corallinus were analyzed by combining snake venomics and venom gland transcriptomic surveys. In both coral snake species, 3FTx and PLA(2) were the most abundant and diversified toxin families. 33 different 3FTxs and 13 PLA(2) proteins, accounting respectively for 79.5% and 13.7% of the total proteins, were identified in the venom of M. altirostris. The venom of M. corallinus comprised 10 3FTx (81.7% of the venom proteome) and 4 (11.9%) PLA(2) molecules. Transcriptomic data provided the full-length amino acid sequences of 18 (M. altirostris) and 10 (M. corallinus) 3FTxs, and 3 (M. altirostris) and 1 (M. corallinus) novel PLA(2) sequences. In addition, venom from each species contained single members of minor toxin families: 3 common (PIII-SVMP, C-type lectin-like, L-amino acid oxidase) and 4 species-specific (CRISP, Kunitz-type inhibitor, lysosomal acid lipase in M. altirostris; serine proteinase in M. corallinus) toxin classes. The finding of a lipase (LIPA) in the venom proteome and in the venom gland transcriptome of M. altirostris supports the view of a recruitment event predating the divergence of Elapidae and Viperidae more than 60 Mya. The toxin profile of both M. altirostris and M. corallinus venoms points to 3FTxs and PLA(2) molecules as the major players of the envenoming process. In M. altirostris venom, all major, and most minor, 3FTxs display highest similarity to type I α-neurotoxins, suggesting that these postsynaptically acting toxins may play the predominant role in the neurotoxic effect leading to peripheral paralysis, respiratory arrest, and death. M. corallinus venom posesses both, type I α-neurotoxins and a high-abundance (26% of the venom proteome) protein of subfamily XIX of 3FTxs, exhibiting similarity to bucandin from Malayan krait, Bungarus candidus, venom, which enhances acetylcholine release presynaptically. This finding may explain the presynaptic neurotoxicity of M. corallinus venom

  20. Venomous snake bites, scorpions, and spiders.

    PubMed

    Kularatne, S A M; Senanayake, Nimal

    2014-01-01

    Neurologic dysfunction due to natural neurotoxins is an important, but neglected, public health hazard in many parts of the world, particularly in the tropics. These toxins are produced by or found among a variety of live forms that include venomous snakes, arthropods such as scorpions, spiders, centipedes, stinging insects (Hymenoptera), ticks, certain poisonous fish, shellfish, crabs, cone shells, skin secretions of dart-poison frogs, and bacterial poisons such as botulinum toxin. These toxins commonly act on neuromuscular transmission at the neuromuscular junction where acetylcholine is the neurotransmitter, but in certain situations the toxins interfere with neurotransmitters such as GABA, noradrenaline, adrenaline, dopamine, and γ-aminobutyrate. Of the toxins, α-toxins and κ-toxins (e.g., Chinese krait, Bungarus multicinctus) act on the postsynaptic membrane, blocking the receptors, whilst β-toxin (e.g., common krait, B. caeruleus) acts on the presynaptic membrane, causing impairment of acetylcholine release. Conversely, dendrotoxins of the African mamba enhance acetylcholine release. The toxins of scorpions and spiders commonly interfere with voltage-gated ion channels. Clinically, the cardinal manifestation is muscle paralysis. In severe cases respiratory paralysis could be fatal. Effective antivenoms are the mainstay of treatment of envenoming, but their lack of availability is the major concern in the regions of the globe where they are desperately needed. Interestingly, some toxins have proved to be valuable pharmaceutical agents, while some others are widely exploited to study neuromuscular physiology and pathology.

  1. Tears of Venom: Hydrodynamics of Reptilian Envenomation

    NASA Astrophysics Data System (ADS)

    Young, Bruce A.; Herzog, Florian; Friedel, Paul; Rammensee, Sebastian; Bausch, Andreas; van Hemmen, J. Leo

    2011-05-01

    In the majority of venomous snakes, and in many other reptiles, venom is conveyed from the animal’s gland to the prey’s tissue through an open groove on the surface of the teeth and not through a tubular fang. Here we focus on two key aspects of the grooved delivery system: the hydrodynamics of venom as it interacts with the groove geometry, and the efficiency of the tooth-groove-venom complex as the tooth penetrates the prey’s tissue. We show that the surface tension of the venom is the driving force underlying the envenomation dynamics. In so doing, we explain not only the efficacy of the open groove, but also the prevalence of this mechanism among reptiles.

  2. Spider-Venom Peptides as Therapeutics

    PubMed Central

    Saez, Natalie J.; Senff, Sebastian; Jensen, Jonas E.; Er, Sing Yan; Herzig, Volker; Rash, Lachlan D.; King, Glenn F.

    2010-01-01

    Spiders are the most successful venomous animals and the most abundant terrestrial predators. Their remarkable success is due in large part to their ingenious exploitation of silk and the evolution of pharmacologically complex venoms that ensure rapid subjugation of prey. Most spider venoms are dominated by disulfide-rich peptides that typically have high affinity and specificity for particular subtypes of ion channels and receptors. Spider venoms are conservatively predicted to contain more than 10 million bioactive peptides, making them a valuable resource for drug discovery. Here we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against a wide range of pathophysiological conditions including cardiovascular disorders, chronic pain, inflammation, and erectile dysfunction. PMID:22069579

  3. Venom: the sharp end of pain therapeutics.

    PubMed

    Trim, Steven A; Trim, Carol M

    2013-11-01

    Adequate pain control is still a significant challenge and largely unmet medical need in the 21st century. With many small molecules failing to reach required levels of potency and selectivity, drug discovery is once again turning to nature to replenish pain therapeutic pipelines. Venomous animals are frequently stereotyped as inflictors of pain and distress and have historically been vilified by mankind. Yet, ironically, the very venoms that cause pain when directly injected by the host animal may actually turn out to contain the next generation of analgesics when injected by the clinician. The last 12 months have seen dramatic discoveries of analgesic tools within venoms. Spiders, snakes and even centipedes are yielding peptides with immense therapeutic potential. Significant advances are also taking place in delivery methods that can improve bioavailability and pharmacokinetics of these exciting natural resources. Turning proteinaceous venom into pharmaceutical liquid gold is the goal of venomics and the focus of this article.

  4. Venom: the sharp end of pain therapeutics

    PubMed Central

    Trim, Carol M

    2013-01-01

    Adequate pain control is still a significant challenge and largely unmet medical need in the 21st century. With many small molecules failing to reach required levels of potency and selectivity, drug discovery is once again turning to nature to replenish pain therapeutic pipelines. Venomous animals are frequently stereotyped as inflictors of pain and distress and have historically been vilified by mankind. Yet, ironically, the very venoms that cause pain when directly injected by the host animal may actually turn out to contain the next generation of analgesics when injected by the clinician. The last 12 months have seen dramatic discoveries of analgesic tools within venoms. Spiders, snakes and even centipedes are yielding peptides with immense therapeutic potential. Significant advances are also taking place in delivery methods that can improve bioavailability and pharmacokinetics of these exciting natural resources. Turning proteinaceous venom into pharmaceutical liquid gold is the goal of venomics and the focus of this article. PMID:26516522

  5. Tears of venom: hydrodynamics of reptilian envenomation.

    PubMed

    Young, Bruce A; Herzog, Florian; Friedel, Paul; Rammensee, Sebastian; Bausch, Andreas; van Hemmen, J Leo

    2011-05-13

    In the majority of venomous snakes, and in many other reptiles, venom is conveyed from the animal's gland to the prey's tissue through an open groove on the surface of the teeth and not through a tubular fang. Here we focus on two key aspects of the grooved delivery system: the hydrodynamics of venom as it interacts with the groove geometry, and the efficiency of the tooth-groove-venom complex as the tooth penetrates the prey's tissue. We show that the surface tension of the venom is the driving force underlying the envenomation dynamics. In so doing, we explain not only the efficacy of the open groove, but also the prevalence of this mechanism among reptiles.

  6. [Bites of venomous snakes in Switzerland].

    PubMed

    Plate, Andreas; Kupferschmidt, Hugo; Schneemann, Markus

    2016-06-08

    Although snake bites are rare in Europe, there are a constant number of snake bites in Switzerland. There are two domestic venomous snakes in Switzerland: the aspic viper (Vipera aspis) and the common European adder (Vipera berus). Bites from venomous snakes are caused either by one of the two domestic venomous snakes or by an exotic venomous snake kept in a terrarium. Snake- bites can cause both a local and/or a systemic envenoming. Potentially fatal systemic complications are related to disturbances of the hemostatic- and cardiovascular system as well as the central or peripheral nervous system. Beside a symptomatic therapy the administration of antivenom is the only causal therapy to neutralize the venomous toxins.

  7. VenomKB, a new knowledge base for facilitating the validation of putative venom therapies

    PubMed Central

    Romano, Joseph D.; Tatonetti, Nicholas P.

    2015-01-01

    Animal venoms have been used for therapeutic purposes since the dawn of recorded history. Only a small fraction, however, have been tested for pharmaceutical utility. Modern computational methods enable the systematic exploration of novel therapeutic uses for venom compounds. Unfortunately, there is currently no comprehensive resource describing the clinical effects of venoms to support this computational analysis. We present VenomKB, a new publicly accessible knowledge base and website that aims to act as a repository for emerging and putative venom therapies. Presently, it consists of three database tables: (1) Manually curated records of putative venom therapies supported by scientific literature, (2) automatically parsed MEDLINE articles describing compounds that may be venom derived, and their effects on the human body, and (3) automatically retrieved records from the new Semantic Medline resource that describe the effects of venom compounds on mammalian anatomy. Data from VenomKB may be selectively retrieved in a variety of popular data formats, are open-source, and will be continually updated as venom therapies become better understood. PMID:26601758

  8. IgE antibodies to bee venom, phospholipase A, melittin and wasp venom.

    PubMed

    Jarisch, R; Yman, L; Boltz, A; Sandor, I; Janitsch, A

    1979-09-01

    Specific IgE antibodies against bee venom, phospholipase A, melittin and wasp venom have been examined in fifty patients with an unusually severe reaction after bee or wasp sting. Two thirds of the bee venom-sensitive patients also have detectable IgE antibodies to wasp venom. More than 50% of the wasp venom-sensitive patients are also allergic to bee venom. Phospholipase A and melittin IgE antibodies were found, respectively, in two thirds and one third of the bee venom-sensitive cases. Specific IgE antibody determinations by the Radioallergosorbent test play an essential role in the diagnostic work. After a reaction to hymenoptera stings both bee and wasp venom tests are necessary due to the high incidence of a false or incomplete identification of the stinging insect. Melittin, known for its potent pharmacological activity and possibly responsible for most of the side effects in bee venom immunotherapy, can probably not be excluded from therapeutic venom preparations since IgE antibodies to the melittin preparation were detected in one third of the cases.

  9. VenomKB, a new knowledge base for facilitating the validation of putative venom therapies.

    PubMed

    Romano, Joseph D; Tatonetti, Nicholas P

    2015-11-24

    Animal venoms have been used for therapeutic purposes since the dawn of recorded history. Only a small fraction, however, have been tested for pharmaceutical utility. Modern computational methods enable the systematic exploration of novel therapeutic uses for venom compounds. Unfortunately, there is currently no comprehensive resource describing the clinical effects of venoms to support this computational analysis. We present VenomKB, a new publicly accessible knowledge base and website that aims to act as a repository for emerging and putative venom therapies. Presently, it consists of three database tables: (1) Manually curated records of putative venom therapies supported by scientific literature, (2) automatically parsed MEDLINE articles describing compounds that may be venom derived, and their effects on the human body, and (3) automatically retrieved records from the new Semantic Medline resource that describe the effects of venom compounds on mammalian anatomy. Data from VenomKB may be selectively retrieved in a variety of popular data formats, are open-source, and will be continually updated as venom therapies become better understood.

  10. Venomics of New World pit vipers: genus-wide comparisons of venom proteomes across Agkistrodon.

    PubMed

    Lomonte, Bruno; Tsai, Wan-Chih; Ureña-Diaz, Juan Manuel; Sanz, Libia; Mora-Obando, Diana; Sánchez, Elda E; Fry, Bryan G; Gutiérrez, José María; Gibbs, H Lisle; Sovic, Michael G; Calvete, Juan J

    2014-01-16

    We report a genus-wide comparison of venom proteome variation across New World pit vipers in the genus Agkistrodon. Despite the wide variety of habitats occupied by this genus and that all its taxa feed on diverse species of vertebrates and invertebrate prey, the venom proteomes of copperheads, cottonmouths, and cantils are remarkably similar, both in the type and relative abundance of their different toxin families. The venoms from all the eleven species and subspecies sampled showed relatively similar proteolytic and PLA2 activities. In contrast, quantitative differences were observed in hemorrhagic and myotoxic activities in mice. The highest myotoxic activity was observed with the venoms of A. b. bilineatus, followed by A. p. piscivorus, whereas the venoms of A. c. contortrix and A. p. leucostoma induced the lowest myotoxic activity. The venoms of Agkistrodon bilineatus subspecies showed the highest hemorrhagic activity and A. c. contortrix the lowest. Compositional and toxicological analyses agree with clinical observations of envenomations by Agkistrodon in the USA and Central America. A comparative analysis of Agkistrodon shows that venom divergence tracks phylogeny of this genus to a greater extent than in Sistrurus rattlesnakes, suggesting that the distinct natural histories of Agkistrodon and Sistrurus clades may have played a key role in molding the patterns of evolution of their venom protein genes. A deep understanding of the structural and functional profiles of venoms and of the principles governing the evolution of venomous systems is a goal of venomics. Isolated proteomics analyses have been conducted on venoms from many species of vipers and pit vipers. However, making sense of these large inventories of data requires the integration of this information across multiple species to identify evolutionary and ecological trends. Our genus-wide venomics study provides a comprehensive overview of the toxic arsenal across Agkistrodon and a ground for

  11. Venomics of New World pit vipers: Genus-wide comparisons of venom proteomes across Agkistrodon

    PubMed Central

    Lomonte, Bruno; Tsai, Wan-Chih; Ureña-Diaz, Juan Manuel; Sanz, Libia; Mora-Obando, Diana; Sánchez, Elda E.; Fry, Bryan G.; Gutiérrez, José María; Gibbs, H. Lisle; Sovic, Michael G.; Calvete, Juan J.

    2015-01-01

    We report a genus-wide comparison of venom proteome variation across New World pit vipers in the genus Agkistrodon. Despite the wide variety of habitats occupied by this genus and that all its taxa feed on diverse species of vertebrates and invertebrate prey, the venom proteomes of copperheads, cottonmouths, and cantils are remarkably similar, both in the type and relative abundance of their different toxin families. The venoms from all the eleven species and subspecies sampled showed relatively similar proteolytic and PLA2 activities. In contrast, quantitative differences were observed in hemorrhagic and myotoxic activities in mice. The highest myotoxic activity was observed with the venoms of A. b. bilineatus, followed by A. p. piscivorus, whereas the venoms of A. c. contortrix and A. p. leucostoma induced the lowest myotoxic activity. The venoms of Agkistrodon bilineatus subspecies showed the highest hemorrhagic activity and A. c. contortrix the lowest. Compositional and toxicological analyses agree with clinical observations of envenomations by Agkistrodon in the USA and Central America. A comparative analysis of Agkistrodon shows that venom divergence tracks phylogeny of this genus to a greater extent than in Sistrurus rattlesnakes, suggesting that the distinct natural histories of Agkistrodon and Sistrurus clades may have played a key role in molding the patterns of evolution of their venom protein genes. Biological significance A deep understanding of the structural and functional profiles of venoms and of the principles governing the evolution of venomous systems is a goal of venomics. Isolated proteomics analyses have been conducted on venoms from many species of vipers and pit vipers. However, making sense of these large inventories of data requires the integration of this information across multiple species to identify evolutionary and ecological trends. Our genus-wide venomics study provides a comprehensive overview of the toxic arsenal across

  12. Exploiting the Nephrotoxic Effects of Venom from the Sea Anemone, Phyllodiscus semoni, to Create a Hemolytic Uremic Syndrome Model in the Rat

    PubMed Central

    Mizuno, Masashi; Ito, Yasuhiko; Morgan, B. Paul

    2012-01-01

    In the natural world, there are many creatures with venoms that have interesting and varied activities. Although the sea anemone, a member of the phylum Coelenterata, has venom that it uses to capture and immobilise small fishes and shrimp and for protection from predators, most sea anemones are harmless to man. However, a few species are highly toxic; some have venoms containing neurotoxins, recently suggested as potential immune-modulators for therapeutic application in immune diseases. Phyllodiscus semoni is a highly toxic sea anemone; the venom has multiple effects, including lethality, hemolysis and renal injuries. We previously reported that venom extracted from Phyllodiscus semoni induced acute glomerular endothelial injuries in rats resembling hemolytic uremic syndrome (HUS), accompanied with complement dysregulation in glomeruli and suggested that the model might be useful for analyses of pathology and development of therapeutic approaches in HUS. In this mini-review, we describe in detail the venom-induced acute renal injuries in rat and summarize how the venom of Phyllodiscus semoni could have potential as a tool for analyses of complement activation and therapeutic interventions in HUS. PMID:22851928

  13. Exploiting the nephrotoxic effects of venom from the sea anemone, Phyllodiscus semoni, to create a hemolytic uremic syndrome model in the rat.

    PubMed

    Mizuno, Masashi; Ito, Yasuhiko; Morgan, B Paul

    2012-07-01

    In the natural world, there are many creatures with venoms that have interesting and varied activities. Although the sea anemone, a member of the phylum Coelenterata, has venom that it uses to capture and immobilise small fishes and shrimp and for protection from predators, most sea anemones are harmless to man. However, a few species are highly toxic; some have venoms containing neurotoxins, recently suggested as potential immune-modulators for therapeutic application in immune diseases. Phyllodiscus semoni is a highly toxic sea anemone; the venom has multiple effects, including lethality, hemolysis and renal injuries. We previously reported that venom extracted from Phyllodiscus semoni induced acute glomerular endothelial injuries in rats resembling hemolytic uremic syndrome (HUS), accompanied with complement dysregulation in glomeruli and suggested that the model might be useful for analyses of pathology and development of therapeutic approaches in HUS. In this mini-review, we describe in detail the venom-induced acute renal injuries in rat and summarize how the venom of Phyllodiscus semoni could have potential as a tool for analyses of complement activation and therapeutic interventions in HUS.

  14. Low cost venom extractor based on Arduino(®) board for electrical venom extraction from arthropods and other small animals.

    PubMed

    Besson, Thomas; Debayle, Delphine; Diochot, Sylvie; Salinas, Miguel; Lingueglia, Eric

    2016-08-01

    Extracting venom from small species is usually challenging. We describe here an affordable and versatile electrical venom extractor based on the Arduino(®) Mega 2560 Board, which is designed to extract venom from arthropods and other small animals. The device includes fine tuning of stimulation time and voltage. It was used to collect venom without apparent deleterious effects, and characterized for the first time the venom of Zoropsis spinimana, a common spider in French Mediterranean regions.

  15. Expression of venom gene homologs in diverse python tissues suggests a new model for the evolution of snake venom.

    PubMed

    Reyes-Velasco, Jacobo; Card, Daren C; Andrew, Audra L; Shaney, Kyle J; Adams, Richard H; Schield, Drew R; Casewell, Nicholas R; Mackessy, Stephen P; Castoe, Todd A

    2015-01-01

    Snake venom gene evolution has been studied intensively over the past several decades, yet most previous studies have lacked the context of complete snake genomes and the full context of gene expression across diverse snake tissues. We took a novel approach to studying snake venom evolution by leveraging the complete genome of the Burmese python, including information from tissue-specific patterns of gene expression. We identified the orthologs of snake venom genes in the python genome, and conducted detailed analysis of gene expression of these venom homologs to identify patterns that differ between snake venom gene families and all other genes. We found that venom gene homologs in the python are expressed in many different tissues outside of oral glands, which illustrates the pitfalls of using transcriptomic data alone to define "venom toxins." We hypothesize that the python may represent an ancestral state prior to major venom development, which is supported by our finding that the expansion of venom gene families is largely restricted to highly venomous caenophidian snakes. Therefore, the python provides insight into biases in which genes were recruited for snake venom systems. Python venom homologs are generally expressed at lower levels, have higher variance among tissues, and are expressed in fewer organs compared with all other python genes. We propose a model for the evolution of snake venoms in which venom genes are recruited preferentially from genes with particular expression profile characteristics, which facilitate a nearly neutral transition toward specialized venom system expression.

  16. Adaptive radiation of venomous marine snail lineages and the accelerated evolution of venom peptide genes

    PubMed Central

    Olivera, Baldomero M.; Watkins, Maren; Bandyopadhyay, Pradip; Imperial, Julita S.; de la Cotera, Edgar P. Heimer; Aguilar, Manuel B.; Vera, Estuardo López; Concepcion, Gisela P.; Lluisma, Arturo

    2012-01-01

    An impressive biodiversity (>10,000 species) of marine snails (suborder Toxoglossa or superfamily Conoidea) have complex venoms, containing ca. 100 biologically active, disulfide-rich peptides. In the genus Conus, the most intensively investigated toxoglossan lineage (~500 species), a small set of venom gene superfamilies undergo rapid sequence hyperdiversification within their mature toxin regions. Each major lineage of Toxoglossa has its own distinct set of venom gene superfamilies. Two recently identified venom gene superfamilies are expressed in the large Turridae clade, but not in Conus. Thus, as major venomous molluscan clades expand, a small set of lineage specific venom gene superfamilies undergo accelerated evolution. The juxtaposition of extremely conserved signal sequences with hypervariable mature peptide regions is unprecedented and raises the possibility that in these gene superfamilies, the signal sequences are conserved as a result of an essential role they play in enabling rapid sequence evolution of the region of the gene that encodes the active toxin. PMID:22954218

  17. Cardiovascular-Active Venom Toxins: An Overview.

    PubMed

    Rebello Horta, Carolina Campolina; Chatzaki, Maria; Rezende, Bruno Almeida; Magalhães, Bárbara de Freitas; Duarte, Clara Guerra; Felicori, Liza Figueiredo; Ribeiro Oliveira-Mendes, Bárbara Bruna; do Carmo, Anderson Oliveira; Chávez-Olórtegui, Carlos; Kalapothakis, Evanguedes

    2016-01-01

    Animal venoms are a mixture of bioactive compounds produced as weapons and used primarily to immobilize and kill preys. As a result of the high potency and specificity for various physiological targets, many toxins from animal venoms have emerged as possible drugs for the medication of diverse disorders, including cardiovascular diseases. Captopril, which inhibits the angiotensin-converting enzyme (ACE), was the first successful venom-based drug and a notable example of rational drug design. Since captopril was developed, many studies have discovered novel bradykinin-potentiating peptides (BPPs) with actions on the cardiovascular system. Natriuretic peptides (NPs) have also been found in animal venoms and used as template to design new drugs with applications in cardiovascular diseases. Among the anti-arrhythmic peptides, GsMTx-4 was discovered to be a toxin that selectively inhibits the stretch-activated cation channels (SACs), which are involved in atrial fibrillation. The present review describes the main components isolated from animal venoms that act on the cardiovascular system and presents a brief summary of venomous animals and their venom apparatuses.

  18. Early significant ontogenetic changes in snake venoms.

    PubMed

    Wray, Kenneth P; Margres, Mark J; Seavy, Margaret; Rokyta, Darin R

    2015-03-01

    Snake venom plays a critical role in food acquisition, digestion, and defense. Venoms are known to change throughout the life of some snake species, but nothing is known about the venom composition of hatchling/neonate snakes prior to and just after their first shedding cycle, despite this being a critical time in the life of the snake. Using a cohort of Crotalus horridus and two cohorts of Crotalus adamanteus, we showed for the first time that snakes undergo significant changes in venom composition after the postnatal shedding event. The number of changes among cohorts ranged widely and there was wide variation in the direction of protein regulation, which appeared to be on a locus-specific level rather than protein-family level. These significant venom composition changes that take place in the first few weeks of life most likely play critical roles in venom economy and resource conservation and may partially explain the rare, post-birth maternal care found in some venomous species.

  19. Venom immunotherapy: an updated review.

    PubMed

    Antolín-Amérigo, Darío; Moreno Aguilar, Carmen; Vega, Arantza; Alvarez-Mon, Melchor

    2014-07-01

    Venom immunotherapy (VIT) is the most effective form of specific immunotherapy to date. Hitherto, several relevant queries remain unanswered, namely optimal doses, duration, and means of assessment. Important progress has been lately made in terms of diagnosis by means of component-resolved diagnosis. Moreover, basophil activation test results in patients with negative serum immunoglobulin E (IgE) and skin prick test confer this technique a promising future, although these outcomes shall be considered with caution. This review aims to unravel the important advances made on diagnosis, management, and prognosis and also focuses on several undetermined aspects of VIT.

  20. Canopy Venom: Proteomic Comparison among New World Arboreal Pit-Viper Venoms

    PubMed Central

    Debono, Jordan; Cochran, Chip; Kuruppu, Sanjaya; Nouwens, Amanda; Rajapakse, Niwanthi W.; Kawasaki, Minami; Wood, Kelly; Dobson, James; Baumann, Kate; Jouiaei, Mahdokht; Jackson, Timothy N. W.; Koludarov, Ivan; Low, Dolyce; Ali, Syed A.; Smith, A. Ian; Barnes, Andrew; Fry, Bryan G.

    2016-01-01

    Central and South American pitvipers, belonging to the genera Bothrops and Bothriechis, have independently evolved arboreal tendencies. Little is known regarding the composition and activity of their venoms. In order to close this knowledge gap, venom proteomics and toxin activity of species of Bothriechis, and Bothrops (including Bothriopsis) were investigated through established analytical methods. A combination of proteomics and bioactivity techniques was used to demonstrate a similar diversification of venom composition between large and small species within Bothriechis and Bothriopsis. Increasing our understanding of the evolution of complex venom cocktails may facilitate future biodiscoveries. PMID:27399777

  1. Hemostatic properties of Venezuelan Bothrops snake venoms with special reference to Bothrops isabelae venom.

    PubMed

    Rodríguez-Acosta, Alexis; Sánchez, Elda E; Márquez, Adriana; Carvajal, Zoila; Salazar, Ana M; Girón, María E; Estrella, Amalid; Gil, Amparo; Guerrero, Belsy

    2010-11-01

    In Venezuela, Bothrops snakes are responsible for more than 80% of all recorded snakebites. This study focuses on the biological and hemostatic characteristics of Bothrops isabelae venom along with its comparative characteristics with two other closely related Bothrops venoms, Bothrops atrox and Bothrops colombiensis. Electrophoretic profiles of crude B. isabelae venom showed protein bands between 14 and 100 kDa with the majority in the range of 14-31 kDa. The molecular exclusion chromatographic profile of this venom contains five fractions (F1-F5). Amidolytic activity evaluation evidenced strong thrombin-like followed by kallikrein-like activities in crude venom and in fractions F1 and F2. The fibrinogenolytic activity of B. isabelae venom at a ratio of 100:1 (fibrinogen/venom) induced a degradation of A alpha and B beta chains at 15 min and 2 h, respectively. At a ratio of 100:10, a total degradation of A alpha and B beta chains at 5 min and of gamma chains at 24 h was apparent. This current study evidences one of rarely reported for Bothrops venoms, which resembles the physiologic effect of plasmin. B. isabelae venom as well as F2 and F3 fractions, contain fibrinolytic activity on fibrin plate of 36, 23.5 and 9.45 mm(2)/microg, respectively using 25 microg of protein. Crude venom and F1 fraction showed gelatinolytic activity. Comparative analysis amongst Venezuelan bothropoid venoms, evidenced that the LD(50) of B. isabelae (5.9 mg/kg) was similar to B. atrox-Puerto Ayacucho 1 (6.1 mg/kg) and B. colombiensis-Caucagua (5.8 mg/kg). B. isabelae venom showed minor hemorrhagic activity, whereas B. atrox-Parguasa (Bolivar state) was the most hemorrhagic. In this study, a relative high thrombin-like activity was observed in B. colombiensis venoms (502-568 mUA/min/mg), and a relative high factor Xa-like activity was found in B. atrox venoms (126-294 mUA/min/mg). Fibrinolytic activity evaluated with 10 microg protein, showed that B. isabelae venom contained higher

  2. Protease inhibitor in scorpion (Mesobuthus eupeus) venom prolongs the biological activities of the crude venom.

    PubMed

    Ma, Hakim; Xiao-Peng, Tang; Yang, Shi-Long; Lu, Qiu-Min; Lai, Ren

    2016-08-01

    It is hypothesized that protease inhibitors play an essential role in survival of venomous animals through protecting peptide/protein toxins from degradation by proteases in their prey or predators. However, the biological function of protease inhibitors in scorpion venoms remains unknown. In the present study, a trypsin inhibitor was purified and characterized from the venom of scorpion Mesobuthus eupeus, which enhanced the biological activities of crude venom components in mice when injected in combination with crude venom. This protease inhibitor, named MeKTT-1, belonged to Kunitz-type toxins subfamily. Native MeKTT-1 selectively inhibited trypsin with a Kivalue of 130 nmol·L(-1). Furthermore, MeKTT-1 was shown to be a thermo-stable peptide. In animal behavioral tests, MeKTT-1 prolonged the pain behavior induced by scorpion crude venom, suggesting that protease inhibitors in scorpion venom inhibited proteases and protect the functionally important peptide/protein toxins from degradation, consequently keeping them active longer. In conclusion, this was the first experimental evidence about the natural existence of serine protease inhibitor in the venom of scorpion Mesobuthus eupeus, which preserved the activity of venom components, suggests that scorpions may use protease inhibitors for survival. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  3. Canopy Venom: Proteomic Comparison among New World Arboreal Pit-Viper Venoms.

    PubMed

    Debono, Jordan; Cochran, Chip; Kuruppu, Sanjaya; Nouwens, Amanda; Rajapakse, Niwanthi W; Kawasaki, Minami; Wood, Kelly; Dobson, James; Baumann, Kate; Jouiaei, Mahdokht; Jackson, Timothy N W; Koludarov, Ivan; Low, Dolyce; Ali, Syed A; Smith, A Ian; Barnes, Andrew; Fry, Bryan G

    2016-07-08

    Central and South American pitvipers, belonging to the genera Bothrops and Bothriechis, have independently evolved arboreal tendencies. Little is known regarding the composition and activity of their venoms. In order to close this knowledge gap, venom proteomics and toxin activity of species of Bothriechis, and Bothrops (including Bothriopsis) were investigated through established analytical methods. A combination of proteomics and bioactivity techniques was used to demonstrate a similar diversification of venom composition between large and small species within Bothriechis and Bothriopsis. Increasing our understanding of the evolution of complex venom cocktails may facilitate future biodiscoveries.

  4. SNAKE VENOMICS OF Crotalus tigris: THE MINIMALIST TOXIN ARSENAL OF THE DEADLIEST NEARTIC RATTLESNAKE VENOM

    PubMed Central

    CALVETE, Juan J.; PÉREZ, Alicia; LOMONTE, Bruno; SÁNCHEZ, Elda E.; SANZ, Libia

    2012-01-01

    We report the proteomic and antivenomic characterization of Crotalus tigris venom. This venom exhibits the highest lethality for mice among rattlesnakes and the simplest toxin proteome reported to date. The venom proteome of C. tigris comprises 7–8 gene products from 6 toxin families: the presynaptic β-neurotoxic heterodimeric PLA2, Mojave toxin, and two serine proteinases comprise, respectively, 66% and 27% of the C. tigris toxin arsenal, whereas a VEGF-like protein, a CRISP molecule, a medium-sized disintegrin, and 1–2 PIII-SVMPs, each represents 0.1–5% of the total venom proteome. This toxin profile really explains the systemic neuro- and myotoxic effects observed in envenomated animals. In addition, we found that venom lethality of C. tigris and other North American rattlesnake type II venoms correlates with the concentration of Mojave toxin A-subunit, supporting the view that the neurotoxic venom phenotype of crotalid type II venoms may be described as a single-allele adaptation. Our data suggest that the evolutionary trend towards neurotoxicity, which has been also reported for the South American rattlesnakes, may have resulted by paedomorphism. The ability of an experimental antivenom to effectively immunodeplete proteins from the type II venoms of C. tigris, C. horridus, C. oreganus helleri, C. scutulatus scutulatus, and S. catenatus catenatus, indicated the feasibility of generating a pan-American anti-Crotalus type II antivenom, suggested by the identification of shared evolutionary trends among South American and North American Crotalus. PMID:22181673

  5. Neutralization of Bothrops alternatus regional venom pools and individual venoms by antivenom: a systematic comparison.

    PubMed

    de Roodt, Adolfo Rafael; Lanari, Laura Cecilia; de Oliveira, Vanessa Costa; Laskowicz, Rodrigo Daniel; Stock, Roberto Pablo

    2011-06-01

    In this study we report that variation in lethality, hemorrhagic potency and procoagulation between individual samples of Bothrops alternatus venom from a single region, and variation between regional pools at the national level are comparable in range. Furthermore, the range of relative neutralization potencies of individual venoms within a region overlaps, and sometimes exceeds, the range of neutralization of regional venom pools throughout the country. Thus, the potency of neutralization of a national venom pool is poorly predictive of the potencies of neutralization of its constituent regional venom pools and, furthermore, the potency of neutralization of a regional venom pool is poorly predictive of the potencies of neutralization of its individual venom constituents. The efficiencies of neutralization of each of these effects (lethality, hemorrhage and procoagulation) were not significantly related to each other and did not correlate to the corresponding toxic potency of each venom or venom pool. Some implications of these findings are discussed in the context of the distinction between experimental quantitation of antivenom potency and the amount of antivenom that might be actually required to successfully treat two apparently comparable B. alternatus envenomations.

  6. The birdlike raptor Sinornithosaurus was venomous

    PubMed Central

    Gong, Enpu; Martin, Larry D.; Burnham, David A.; Falk, Amanda R.

    2009-01-01

    We suggest that some of the most avian dromaeosaurs, such as Sinornithosaurus, were venomous, and propose an ecological model for that taxon based on its unusual dentition and other cranial features including grooved teeth, a possible pocket for venom glands, and a groove leading from that pocket to the exposed bases of the teeth. These features are all analogous to the venomous morphology of lizards. Sinornithosaurus and related dromaeosaurs probably fed on the abundant birds of the Jehol forests during the Early Cretaceous in northeastern China. PMID:20080749

  7. The birdlike raptor Sinornithosaurus was venomous.

    PubMed

    Gong, Enpu; Martin, Larry D; Burnham, David A; Falk, Amanda R

    2010-01-12

    We suggest that some of the most avian dromaeosaurs, such as Sinornithosaurus, were venomous, and propose an ecological model for that taxon based on its unusual dentition and other cranial features including grooved teeth, a possible pocket for venom glands, and a groove leading from that pocket to the exposed bases of the teeth. These features are all analogous to the venomous morphology of lizards. Sinornithosaurus and related dromaeosaurs probably fed on the abundant birds of the Jehol forests during the Early Cretaceous in northeastern China.

  8. Cholinergic antagonists in a solitary wasp venom.

    PubMed

    Piek, T; Mantel, P

    1986-01-01

    The venom of the solitary wasp Philanthus triangulum contains a cholinergic antagonist of the nicotinic receptor of the rectus abdominis muscle of the frog, Xenopus laevis. The venom of African P. triangulum contains two different cholinergic factors, a competitive and a non-competitive antagonist. The venom of the European P. triangulum may not contain a competitive antagonist of the nicotinic receptor of X. laevis, but only a very strong non-competitive antagonist. The possible non-synonymity of both groups of P. triangulum is discussed.

  9. Putting the brakes on snake venom evolution: the unique molecular evolutionary patterns of Aipysurus eydouxii (Marbled sea snake) phospholipase A2 toxins.

    PubMed

    Li, Min; Fry, Bryan G; Kini, R Manjunatha

    2005-04-01

    Accelerated evolution of toxins is a unique feature of venoms, with the toxins evolving via the birth-and-death mode of molecular evolution. The venoms of sea snakes, however, are remarkably simple in comparison to those of land snakes, which contain highly complex venoms. Aipysurus eydouxii (Marbled sea snake) is a particularly unique sea snake, feeding exclusively upon fish eggs. Secondary to this ecological change, the fangs have been lost and the venom glands greatly atrophied. We recently showed that the only neurotoxin (a three-finger toxin) gene found in the sea snake A. eydouxii has a dinucleotide deletion, resulting in the loss of neurotoxic activity. During these studies, we isolated and identified a number of cDNA clones encoding isozymes of phospholipase A(2) (PLA(2)) toxins from its venom gland. Sixteen unique PLA(2) clones were sequenced from the cDNA library and TA cloning of reverse transcription-polymerase chain reaction products. Phylogenetic analysis of these clones revealed that less diversification of the PLA(2) toxins has occurred in the A. eydouxii venom gland in comparison to equivalent terrestrial and other marine snakes. As there is no longer a positive selection pressure acting upon the venom, mutations have accumulated in the toxin-coding regions that would have otherwise had a deleterious effect upon the ability to use the venom for prey capture. Such mutations include substitutions of highly conserved residues; in one clone, the active site His(48) is replaced by Arg, and in two other clones, highly conserved cysteine residues are replaced. These mutations significantly affect the functional and structural properties of these PLA(2) enzymes, respectively. Thus, in A. eydouxii, the loss of the main neurotoxin is accompanied by a much slower rate of molecular evolution of the PLA(2) toxins as a consequence of the snake's shift in ecological niche. This is the first case of decelerated evolution of toxins in snake venom.

  10. Preliminary Study on Nematocyst Types and Venom Isolation of Cassiopea andromeda Forskål, 1775 (Scyphozoa, Cnidaria) from Turkey.

    PubMed

    Gülşahin, Nurçin

    2016-01-01

    Nematocyst types of Cassiopea andromeda were investigated. Medusae samples were taken from Güllük Bay, Muğla, Turkey. Nematocyst samples from oral arms of C. andromeda were observed on light microscope and photographed. Birhopaloid and a-isorhiza nematocyst types were found in C. andromeda. Moreover, it was seen that nematocyst sizes increased with increasing the bell diameters of the individuals. Also, the venom of the species was isolated and injected intramuscularly to Cyprinus carpio juveniles. Signs of partial paralysis, raking, and immobilized fins were observed in the juveniles consequently. Death was observed for the fishes which were 3-4 g in the range of weight. This study is a preliminary work on nematocysts and venom of C. andromeda. Further studies on neurotoxic effects of nematocyst venoms of this species should follow.

  11. Diversification rates and phenotypic evolution in venomous snakes (Elapidae).

    PubMed

    Lee, Michael S Y; Sanders, Kate L; King, Benedict; Palci, Alessandro

    2016-01-01

    The relationship between rates of diversification and of body size change (a common proxy for phenotypic evolution) was investigated across Elapidae, the largest radiation of highly venomous snakes. Time-calibrated phylogenetic trees for 175 species of elapids (more than 50% of known taxa) were constructed using seven mitochondrial and nuclear genes. Analyses using these trees revealed no evidence for a link between speciation rates and changes in body size. Two clades (Hydrophis, Micrurus) show anomalously high rates of diversification within Elapidae, yet exhibit rates of body size evolution almost identical to the general elapid 'background' rate. Although correlations between speciation rates and rates of body size change exist in certain groups (e.g. ray-finned fishes, passerine birds), the two processes appear to be uncoupled in elapid snakes. There is also no detectable shift in diversification dynamics associated with the colonization of Australasia, which is surprising given that elapids appear to be the first clade of venomous snakes to reach the continent.

  12. Diversification rates and phenotypic evolution in venomous snakes (Elapidae)

    PubMed Central

    Lee, Michael S. Y.; Sanders, Kate L.; King, Benedict; Palci, Alessandro

    2016-01-01

    The relationship between rates of diversification and of body size change (a common proxy for phenotypic evolution) was investigated across Elapidae, the largest radiation of highly venomous snakes. Time-calibrated phylogenetic trees for 175 species of elapids (more than 50% of known taxa) were constructed using seven mitochondrial and nuclear genes. Analyses using these trees revealed no evidence for a link between speciation rates and changes in body size. Two clades (Hydrophis, Micrurus) show anomalously high rates of diversification within Elapidae, yet exhibit rates of body size evolution almost identical to the general elapid ‘background’ rate. Although correlations between speciation rates and rates of body size change exist in certain groups (e.g. ray-finned fishes, passerine birds), the two processes appear to be uncoupled in elapid snakes. There is also no detectable shift in diversification dynamics associated with the colonization of Australasia, which is surprising given that elapids appear to be the first clade of venomous snakes to reach the continent. PMID:26909162

  13. Ecological venomics: How genomics, transcriptomics and proteomics can shed new light on the ecology and evolution of venom.

    PubMed

    Sunagar, Kartik; Morgenstern, David; Reitzel, Adam M; Moran, Yehu

    2016-03-01

    Animal venom is a complex cocktail of bioactive chemicals that traditionally drew interest mostly from biochemists and pharmacologists. However, in recent years the evolutionary and ecological importance of venom is realized as this trait has direct and strong influence on interactions between species. Moreover, venom content can be modulated by environmental factors. Like many other fields of biology, venom research has been revolutionized in recent years by the introduction of systems biology approaches, i.e., genomics, transcriptomics and proteomics. The employment of these methods in venom research is known as 'venomics'. In this review we describe the history and recent advancements of venomics and discuss how they are employed in studying venom in general and in particular in the context of evolutionary ecology. We also discuss the pitfalls and challenges of venomics and what the future may hold for this emerging scientific field. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Characterizing Tityus discrepans scorpion venom from a fractal perspective: Venom complexity, effects of captivity, sexual dimorphism, differences among species.

    PubMed

    D'Suze, Gina; Sandoval, Moisés; Sevcik, Carlos

    2015-12-15

    A characteristic of venom elution patterns, shared with many other complex systems, is that many their features cannot be properly described with statistical or euclidean concepts. The understanding of such systems became possible with Mandelbrot's fractal analysis. Venom elution patterns were produced using the reversed phase high performance liquid chromatography (HPLC) with 1 mg of venom. One reason for the lack of quantitative analyses of the sources of venom variability is parametrizing the venom chromatograms' complexity. We quantize this complexity by means of an algorithm which estimates the contortedness (Q) of a waveform. Fractal analysis was used to compare venoms and to measure inter- and intra-specific venom variability. We studied variations in venom complexity derived from gender, seasonal and environmental factors, duration of captivity in the laboratory, technique used to milk venom. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Extreme diversity of scorpion venom peptides and proteins revealed by transcriptomic analysis: implication for proteome evolution of scorpion venom arsenal.

    PubMed

    Ma, Yibao; He, Yawen; Zhao, Ruiming; Wu, Yingliang; Li, Wenxin; Cao, Zhijian

    2012-02-16

    Venom is an important genetic development crucial to the survival of scorpions for over 400 million years. We studied the evolution of the scorpion venom arsenal by means of comparative transcriptome analysis of venom glands and phylogenetic analysis of shared types of venom peptides and proteins between buthids and euscorpiids. Fifteen types of venom peptides and proteins were sequenced during the venom gland transcriptome analyses of two Buthidae species (Lychas mucronatus and Isometrus maculatus) and one Euscorpiidae species (Scorpiops margerisonae). Great diversity has been observed in translated amino acid sequences of these transcripts for venom peptides and proteins. Seven types of venom peptides and proteins were shared between buthids and euscorpiids. Molecular phylogenetic analysis revealed that at least five of the seven common types of venom peptides and proteins were likely recruited into the scorpion venom proteome before the lineage split between Buthidae and Euscorpiidae with their corresponding genes undergoing individual or multiple gene duplication events. These are α-KTxs, βKSPNs (β-KTxs and scorpines), anionic peptides, La1-like peptides, and SPSVs (serine proteases from scorpion venom). Multiple types of venom peptides and proteins were demonstrated to be continuously recruited into the venom proteome during the evolution process of individual scorpion lineages. Our results provide an insight into the recruitment pattern of the scorpion venom arsenal for the first time.

  16. Inhibition of Hemorragic Snake Venom Components: Old and New Approaches

    PubMed Central

    Panfoli, Isabella; Calzia, Daniela; Ravera, Silvia; Morelli, Alessandro

    2010-01-01

    Snake venoms are complex toxin mixtures. Viperidae and Crotalidae venoms, which are hemotoxic, are responsible for most of the envenomations around the world. Administration of antivenins aimed at the neutralization of toxins in humans is prone to potential risks. Neutralization of snake venom toxins has been achieved through different approaches: plant extracts have been utilized in etnomedicine. Direct electric current from low voltage showed neutralizing properties against venom phospholipase A2 and metalloproteases. This mini-review summarizes new achievements in venom key component inhibition. A deeper knowledge of alternative ways to inhibit venom toxins may provide supplemental treatments to serum therapy. PMID:22069593

  17. Hemostatic interference of Indian king cobra (Ophiophagus hannah) Venom. Comparison with three other snake venoms of the subcontinent.

    PubMed

    Gowtham, Yashonandana J; Kumar, M S; Girish, K S; Kemparaju, K

    2012-06-01

    Unlike Naja naja, Bungarus caeruleus, Echis carinatus, and Daboia/Vipera russellii venoms, Ophiophagus hannah venom is medically ignored in the Indian subcontinent. Being the biggest poisonous snake, O. hannah has been presumed to inject several lethal doses of venom in a single bite. Lack of therapeutic antivenom to O. hannah bite in India makes any attempt to save the victim a difficult exercise. This study was initiated to compare O. hannah venom with the above said venoms for possible interference in hemostasis. Ophiophagus hannah venom was found to actively interfere in hemostatic stages such as fibrin clot formation, platelet activation/aggregation, and fibrin clot dissolution. It decreased partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin clotting time (TCT). These activities are similar to that shown by E. carinatus and D. russellii venoms, and thus O. hannah venom was found to exert procoagulant activity through the common pathway of blood coagulation, while N. naja venom increased aPTT and TCT but not PT, and hence it was found to exert anticoagulant activity through the intrinsic pathway. Venoms of O. hannah, E. carinatus, and D. russellii lack plasminogen activation property as they do not hydrolyze azocasein, while they all show plasmin-like activity by degrading the fibrin clot. Although N. naja venom did not degrade azocasein, unlike other venoms, it showed feeble plasmin-like activity on fibrin clot. Venom of E. carinatus induced clotting of human platelet rich plasma (PRP), while the other three venoms interfered in agonist-induced platelet aggregation in PRP. Venom of O. hannah least inhibited the ADP induced platelet aggregation as compared to D. russellii and N. naja venoms. All these three venoms showed complete inhibition of epinephrine-induced aggregation at varied doses. However, O. hannah venom was unique in inhibiting thrombin induced aggregation.

  18. Bothrops fonsecai snake venom activities and cross-reactivity with commercial bothropic venom.

    PubMed

    Collaço, Rita de Cássia O; Randazzo-Moura, Priscila; Tamascia, Mariana L; da Silva, Igor Rapp F; Rocha, Thalita; Cogo, José C; Hyslop, Stephen; Sanny, Charles G; Rodrigues-Simioni, Léa

    2017-01-01

    In this work, we examined some biochemical and biological activities of Bothrops fonsecai venom, a pitviper endemic to southeastern Brazil, and assessed their neutralization by commercial bothropic antivenom (CAv). Cross-reactivity of venom with CAv was also assessed by immunoblotting and size-exclusion high performance chromatography (SE-HPLC). Bothrops fonsecai venom had PLA2, proteolytic and esterase activities that were neutralized to varying extents by venom:antivenom ratios of 5:1 and 5:2 (PLA2 and esterase activities) or not significantly by either venom:antivenom ratio (proteolytic activity). The minimum hemorrhagic dose (69.2μg) was totally neutralized by both ratios. Clotting time in rat citrated plasma was 33±10.5s (mean±SD; n=5) and was completely neutralized by a 5:2 ratio. Edema formation was dose-dependent (1-30μg/site) and significantly inhibited by both ratios. Venom (10-300μg/mL) caused neuromuscular blockade in extensor digitorum longus preparations; this blockade was inhibited best by a 5:2 ratio. Venom caused myonecrosis and creatine kinase release in vivo (gastrocnemius muscle) and in vitro (extensor digitorum longus) that was effectively neutralized by both venom:antivenom ratios. Immunoblotting showed that venom components of ~25-100kDa interacted with CAv. SE-HPLC profiles for venom incubated with CAv or specific anti-B. fonsecai antivenom raised in rabbits (SAv) indicated that CAv had a higher binding capacity than SAv, whereas SAv had higher affinity than CAv. These findings indicate that B. fonsecai venom contains various activities that are neutralized to different extents by CAv and suggest that CAv could be used to treat envenoming by B. fonsecai.

  19. Echidna venom gland transcriptome provides insights into the evolution of monotreme venom.

    PubMed

    Wong, Emily S W; Nicol, Stewart; Warren, Wesley C; Belov, Katherine

    2013-01-01

    Monotremes (echidna and platypus) are egg-laying mammals. One of their most unique characteristic is that males have venom/crural glands that are seasonally active. Male platypuses produce venom during the breeding season, delivered via spurs, to aid in competition against other males. Echidnas are not able to erect their spurs, but a milky secretion is produced by the gland during the breeding season. The function and molecular composition of echidna venom is as yet unknown. Hence, we compared the deeply sequenced transcriptome of an in-season echidna crural gland to that of a platypus and searched for putative venom genes to provide clues into the function of echidna venom and the evolutionary history of monotreme venom. We found that the echidna venom gland transcriptome was markedly different from the platypus with no correlation between the top 50 most highly expressed genes. Four peptides found in the venom of the platypus were detected in the echidna transcriptome. However, these genes were not highly expressed in echidna, suggesting that they are the remnants of the evolutionary history of the ancestral venom gland. Gene ontology terms associated with the top 100 most highly expressed genes in echidna, showed functional terms associated with steroidal and fatty acid production, suggesting that echidna "venom" may play a role in scent communication during the breeding season. The loss of the ability to erect the spur and other unknown evolutionary forces acting in the echidna lineage resulted in the gradual decay of venom components and the evolution of a new role for the crural gland.

  20. Venom-based biotoxins as potential analgesics.

    PubMed

    Gazerani, Parisa; Cairns, Brian Edwin

    2014-11-01

    Chronic pain is a common debilitating condition with negative social and economic consequences. Management of chronic pain is challenging and the currently available medications do not yet yield satisfactory outcomes for many patients. Venom-derived biotoxins from various venomous species consist of several substances with different structures and compositions that include peptides. A unique characteristic of some venom-based biotoxins is the ability to block essential components of the pain signaling system, notably ion channels. This property is leading to the evaluation of the potential of biotoxins as analgesics to manage chronic pain. In addition to their therapeutic potential, biotoxins have also been essential tools to probe mechanisms underlying pain signaling, channelopathies and receptor expression. This review discusses venom-derived peptidergic biotoxins that are in preclinical stages or already in clinical trials. Some promising results from preliminary in vitro studies, ongoing challenges and unmet needs will also be discussed.

  1. Genetic mechanisms of scorpion venom peptide diversification.

    PubMed

    Zhijian, Cao; Feng, Luo; Yingliang, Wu; Xin, Mao; Wenxin, Li

    2006-03-01

    The diversity of scorpion venom peptides is well shown by the presence of about 400 such polypeptides with or without disulfide bonds. Scorpion toxins with disulfide bonds present a variety of sequence features and pharmacological functions by affecting different ion channels, while the venom peptides without disulfide bonds represent a new subfamily, having much lower sequence homology among each other and different functions (e.g. bradykinin-potentiating, antimicrobial, molecular cell signal initiating and immune modulating). Interestingly, all scorpion venom peptides with divergent functions may have evolved from a common ancestor gene. Over the lengthy evolutionary time, the diversification of scorpion venom peptides evolved through polymorphism, duplication, trans-splicing, or alternative splicing at the gene level. In order to completely clarify the diversity of scorpion toxins and toxin-like peptides, toxinomics (genomics and proteomics of scorpion toxins and toxin-like peptides) are expected to greatly advance in the near future.

  2. The mitochondrial genome of the venomous cone snail Conus consors.

    PubMed

    Brauer, Age; Kurz, Alexander; Stockwell, Tim; Baden-Tillson, Holly; Heidler, Juliana; Wittig, Ilka; Kauferstein, Silke; Mebs, Dietrich; Stöcklin, Reto; Remm, Maido

    2012-01-01

    Cone snails are venomous predatory marine neogastropods that belong to the species-rich superfamily of the Conoidea. So far, the mitochondrial genomes of two cone snail species (Conus textile and Conus borgesi) have been described, and these feed on snails and worms, respectively. Here, we report the mitochondrial genome sequence of the fish-hunting cone snail Conus consors and describe a novel putative control region (CR) which seems to be absent in the mitochondrial DNA (mtDNA) of other cone snail species. This possible CR spans about 700 base pairs (bp) and is located between the genes encoding the transfer RNA for phenylalanine (tRNA-Phe, trnF) and cytochrome c oxidase subunit III (cox3). The novel putative CR contains several sequence motifs that suggest a role in mitochondrial replication and transcription.

  3. The Mitochondrial Genome of the Venomous Cone Snail Conus consors

    PubMed Central

    Brauer, Age; Kurz, Alexander; Stockwell, Tim; Baden-Tillson, Holly; Heidler, Juliana; Wittig, Ilka; Kauferstein, Silke; Mebs, Dietrich; Stöcklin, Reto; Remm, Maido

    2012-01-01

    Cone snails are venomous predatory marine neogastropods that belong to the species-rich superfamily of the Conoidea. So far, the mitochondrial genomes of two cone snail species (Conus textile and Conus borgesi) have been described, and these feed on snails and worms, respectively. Here, we report the mitochondrial genome sequence of the fish-hunting cone snail Conus consors and describe a novel putative control region (CR) which seems to be absent in the mitochondrial DNA (mtDNA) of other cone snail species. This possible CR spans about 700 base pairs (bp) and is located between the genes encoding the transfer RNA for phenylalanine (tRNA-Phe, trnF) and cytochrome c oxidase subunit III (cox3). The novel putative CR contains several sequence motifs that suggest a role in mitochondrial replication and transcription. PMID:23236512

  4. Biological characterization of Bothrops marajoensis snake venom

    PubMed Central

    Cavalcante, Walter LG; Hernandez-Oliveira, Saraguaci; Galbiatti, Charlene; Randazzo-Moura, Priscila; Rocha, Thalita; Ponce-Soto, Luis; Marangoni, Sérgio; Pai-Silva, Maeli Dal; Gallacci, Márcia; da Cruz-Höfling, Maria A; Rodrigues-Simioni, Léa

    2011-01-01

    This study describes the effects of Bothrops marajoensis venom (Marajó lancehead) on isolated neuromuscular preparations of chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND). At low concentrations (1µg/ml for CBC and 5µg/ml for PND), the venom exhibited a neuromuscular blocking without any damaging effect on the muscle integrity. At higher concentration (20μg/ml for PND), together with the neuromuscular blockade, there was a moderate myonecrosis. The results show differences between mammalian and avian preparations in response to venom concentration; the avian preparation was more sensitive to venom neurotoxic effect than the mammalian preparation. The possible presynaptic mechanism underlying the neuromuscular blocking effect was reinforced by the observed increase in MEPPs at the same time (at 15min) when the facilitation of twitch tension occurred. These results indicate that the B. marajoensis venom produced neuromuscular blockade, which appeared to be presynaptic at low concentrations with a postsynaptic component at high concentrations, leading to muscle oedema. These observations demand the fractionation of the crude venom and characterization of its active components for a better understanding of its biological dynamics. PMID:22091348

  5. Snake venom. The amino acid sequence of protein A from Dendroaspis polylepis polylepis (black mamba) venom.

    PubMed

    Joubert, F J; Strydom, D J

    1980-12-01

    Protein A from Dendroaspis polylepis polylepis venom comprises 81 amino acids, including ten half-cystine residues. The complete primary structures of protein A and its variant A' were elucidated. The sequences of proteins A and A', which differ in a single position, show no homology with various neurotoxins and non-neurotoxic proteins and represent a new type of elapid venom protein.

  6. Black Bear Reactions to Venomous and Non-venomous Snakes in Eastern North America.

    PubMed

    Rogers, Lynn L; Mansfield, Susan A; Hornby, Kathleen; Hornby, Stewart; Debruyn, Terry D; Mize, Malvin; Clark, Rulon; Burghardt, Gordon M

    2014-07-01

    Bears are often considered ecological equivalents of large primates, but the latter often respond with fear, avoidance, and alarm calls to snakes, both venomous and non-venomous, there is sparse information on how bears respond to snakes. We videotaped or directly observed natural encounters between black bears (Ursus americanus) and snakes. Inside the range of venomous snakes in Arkansas and West Virginia, adolescent and adult black bears reacted fearfully in seven of seven encounters upon becoming aware of venomous and non-venomous snakes; but in northern Michigan and Minnesota where venomous snakes have been absent for millennia, black bears showed little or no fear in four encounters with non-venomous snakes of three species. The possible roles of experience and evolution in bear reactions to snakes and vice versa are discussed. In all areas studied, black bears had difficulty to recognize non-moving snakes by smell or sight. Bears did not react until snakes moved in 11 of 12 encounters with non-moving timber rattlesnakes (Crotalus horridus) and four species of harmless snakes. However, in additional tests in this study, bears were repulsed by garter snakes that had excreted pungent anal exudates, which may help explain the absence of snakes, both venomous and harmless, in bear diets reported to date.

  7. Black Bear Reactions to Venomous and Non-venomous Snakes in Eastern North America

    PubMed Central

    Rogers, Lynn L; Mansfield, Susan A; Hornby, Kathleen; Hornby, Stewart; Debruyn, Terry D; Mize, Malvin; Clark, Rulon; Burghardt, Gordon M

    2014-01-01

    Bears are often considered ecological equivalents of large primates, but the latter often respond with fear, avoidance, and alarm calls to snakes, both venomous and non-venomous, there is sparse information on how bears respond to snakes. We videotaped or directly observed natural encounters between black bears (Ursus americanus) and snakes. Inside the range of venomous snakes in Arkansas and West Virginia, adolescent and adult black bears reacted fearfully in seven of seven encounters upon becoming aware of venomous and non-venomous snakes; but in northern Michigan and Minnesota where venomous snakes have been absent for millennia, black bears showed little or no fear in four encounters with non-venomous snakes of three species. The possible roles of experience and evolution in bear reactions to snakes and vice versa are discussed. In all areas studied, black bears had difficulty to recognize non-moving snakes by smell or sight. Bears did not react until snakes moved in 11 of 12 encounters with non-moving timber rattlesnakes (Crotalus horridus) and four species of harmless snakes. However, in additional tests in this study, bears were repulsed by garter snakes that had excreted pungent anal exudates, which may help explain the absence of snakes, both venomous and harmless, in bear diets reported to date. PMID:25635152

  8. Vintage venoms: proteomic and pharmacological stability of snake venoms stored for up to eight decades.

    PubMed

    Jesupret, Clémence; Baumann, Kate; Jackson, Timothy N W; Ali, Syed Abid; Yang, Daryl C; Greisman, Laura; Kern, Larissa; Steuten, Jessica; Jouiaei, Mahdokht; Casewell, Nicholas R; Undheim, Eivind A B; Koludarov, Ivan; Debono, Jordan; Low, Dolyce H W; Rossi, Sarah; Panagides, Nadya; Winter, Kelly; Ignjatovic, Vera; Summerhayes, Robyn; Jones, Alun; Nouwens, Amanda; Dunstan, Nathan; Hodgson, Wayne C; Winkel, Kenneth D; Monagle, Paul; Fry, Bryan Grieg

    2014-06-13

    For over a century, venom samples from wild snakes have been collected and stored around the world. However, the quality of storage conditions for "vintage" venoms has rarely been assessed. The goal of this study was to determine whether such historical venom samples are still biochemically and pharmacologically viable for research purposes, or if new sample efforts are needed. In total, 52 samples spanning 5 genera and 13 species with regional variants of some species (e.g., 14 different populations of Notechis scutatus) were analysed by a combined proteomic and pharmacological approach to determine protein structural stability and bioactivity. When venoms were not exposed to air during storage, the proteomic results were virtually indistinguishable from that of fresh venom and bioactivity was equivalent or only slightly reduced. By contrast, a sample of Acanthophis antarcticus venom that was exposed to air (due to a loss of integrity of the rubber stopper) suffered significant degradation as evidenced by the proteomics profile. Interestingly, the neurotoxicity of this sample was nearly the same as fresh venom, indicating that degradation may have occurred in the free N- or C-terminus chains of the proteins, rather than at the tips of loops where the functional residues are located. These results suggest that these and other vintage venom collections may be of continuing value in toxin research. This is particularly important as many snake species worldwide are declining due to habitat destruction or modification. For some venoms (such as N. scutatus from Babel Island, Flinders Island, King Island and St. Francis Island) these were the first analyses ever conducted and these vintage samples may represent the only venom ever collected from these unique island forms of tiger snakes. Such vintage venoms may therefore represent the last remaining stocks of some local populations and thus are precious resources. These venoms also have significant historical value as

  9. Venom-gland transcriptome and venom proteome of the Malaysian king cobra (Ophiophagus hannah).

    PubMed

    Tan, Choo Hock; Tan, Kae Yi; Fung, Shin Yee; Tan, Nget Hong

    2015-09-10

    The king cobra (Ophiophagus hannah) is widely distributed throughout many parts of Asia. This study aims to investigate the complexity of Malaysian Ophiophagus hannah (MOh) venom for a better understanding of king cobra venom variation and its envenoming pathophysiology. The venom gland transcriptome was investigated using the Illumina HiSeq™ platform, while the venom proteome was profiled by 1D-SDS-PAGE-nano-ESI-LCMS/MS. Transcriptomic results reveal high redundancy of toxin transcripts (3357.36 FPKM/transcript) despite small cluster numbers, implying gene duplication and diversification within restricted protein families. Among the 23 toxin families identified, three-finger toxins (3FTxs) and snake-venom metalloproteases (SVMPs) have the most diverse isoforms. These 2 toxin families are also the most abundantly transcribed, followed in descending order by phospholipases A2 (PLA2s), cysteine-rich secretory proteins (CRISPs), Kunitz-type inhibitors (KUNs), and L-amino acid oxidases (LAAOs). Seventeen toxin families exhibited low mRNA expression, including hyaluronidase, DPP-IV and 5'-nucleotidase that were not previously reported in the venom-gland transcriptome of a Balinese O. hannah. On the other hand, the MOh proteome includes 3FTxs, the most abundantly expressed proteins in the venom (43 % toxin sbundance). Within this toxin family, there are 6 long-chain, 5 short-chain and 2 non-conventional 3FTx. Neurotoxins comprise the major 3FTxs in the MOh venom, consistent with rapid neuromuscular paralysis reported in systemic envenoming. The presence of toxic enzymes such as LAAOs, SVMPs and PLA2 would explain tissue inflammation and necrotising destruction in local envenoming. Dissimilarities in the subtypes and sequences between the neurotoxins of MOh and Naja kaouthia (monocled cobra) are in agreement with the poor cross-neutralization activity of N. kaouthia antivenom used against MOh venom. Besides, the presence of cobra venom factor, nerve growth factors

  10. Anti-venom potential of butanolic extract of Eclipta prostrata against Malayan pit viper venom.

    PubMed

    Pithayanukul, Pimolpan; Laovachirasuwan, Sasitorn; Bavovada, Rapepol; Pakmanee, Narumol; Suttisri, Rutt

    2004-02-01

    The butanolic and purified butanolic extracts (PBEs) of Eclipta prostrata were evaluated for their anti-venom potential. Inhibition of lethal, hemorrhagic, proteolytic, and phospholipase A2 activities of Calloselasma rhodostoma (Malayan pit viper (MPV)) venom by these extracts were determined. Demethylwedelolactone was identified as their major constituent. The butanolic extract, at 2.5 mg per mouse, was able to completely neutralize the lethal activity of 2LD50 of MPV venom, but increasing the dose diminished the effect. The PBE, at 1.5-4.5 mg per mouse, was able to neutralize the lethality of the venom at around 50-58%. Both extracts partially inhibited the hemorrhagic activity but displayed very low anti-phospholipase A2 activity and did not inhibit proteolytic activity of MPV venom.

  11. Shortage of Bee, Wasp Venom Stings Those with Allergies

    MedlinePlus

    ... gov/news/fullstory_167081.html Shortage of Bee, Wasp Venom Stings Those With Allergies Facing expected season- ... 7, 2017 (HealthDay News) -- A shortage of honeybee, wasp and hornet venom extract has allergists concerned. The ...

  12. Unraveling snake venom complexity with 'omics' approaches: challenges and perspectives.

    PubMed

    Zelanis, André; Tashima, Alexandre Keiji

    2014-09-01

    The study of snake venom proteomes (venomics) has been experiencing a burst of reports, however the comprehensive knowledge of the dynamic range of proteins present within a single venom, the set of post-translational modifications (PTMs) as well as the lack of a comprehensive database related to venom proteins are among the main challenges in venomics research. The phenotypic plasticity in snake venom proteomes together with their inherent toxin proteoform diversity, points out to the use of integrative analysis in order to better understand their actual complexity. In this regard, such a systems venomics task should encompass the integration of data from transcriptomic and proteomic studies (specially the venom gland proteome), the identification of biological PTMs, and the estimation of artifactual proteomes and peptidomes generated by sample handling procedures.

  13. Neutralization of cobra venom by cocktail antiserum against venom proteins of cobra (Naja naja naja).

    PubMed

    Venkatesan, C; Sarathi, M; Balasubramanaiyan, G; Vimal, S; Madan, N; Sundar Raj, N; Mohammed Yusuf Bilal, S; Nazeer Basha, A; Farook, M A; Sahul Hameed, A S; Sridevi, G

    2014-01-01

    Naja naja venom was characterized by its immunochemical properties and electrophoretic pattern which revealed eight protein bands (14 kDa, 24 kDa, 29 kDa, 45 kDa, 48 kDa, 65 kDa, 72 kDa and 99 kDa) by SDS-PAGE in reducing condition after staining with Coomassie Brilliant Blue. The results showed that Naja venom presented high lethal activity. Whole venom antiserum or individual venom protein antiserum (14 kDa, 29 kDa, 65 kDa, 72 kDa and 99 kDa) of venom could recognize N. naja venom by Western blotting and ELISA, and N. naja venom presented antibody titer when assayed by ELISA. The neutralization tests showed that the polyvalent antiserum neutralized lethal activities by both in vivo and in vitro studies using mice and Vero cells. The antiserum could neutralize the lethal activities in in-vivo and antivenom administered after injection of cobra venom through intraperitoneal route in mice. The cocktail antiserum also could neutralize the cytotoxic activities in Vero cell line by MTT and Neutral red assays. The results of the present study suggest that cocktail antiserum neutralizes the lethal activities in both in vitro and in vivo models using the antiserum against cobra venom and its individual venom proteins serum produced in rabbits. Copyright © 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  14. Development of dot-ELISA for the detection of venoms of major Indian venomous snakes.

    PubMed

    Shaikh, Innus K; Dixit, Prashant P; Pawade, Balasaheb S; Waykar, Indrasen G

    2017-10-09

    India remained an epicenter for the snakebite-related mortality and morbidities due to widespread agricultural activities across the country and a considerable number of snakebites offended by Indian cobra (Naja naja), common krait (Bungarus caeruleus), Russell's viper (Daboia russelii), and saw-scaled viper (Echis carinatus). Presently, there is no selective test available for the detection of snake envenomation in India before the administration of snake antivenin. Therefore, the present study aimed to develop rapid, sensitive assay for the management of snakebite, which can detect venom, responsible snake species and serve as a tool for the reasonable administration of snake antivenin, which have scarcity across the world. The selective envenomation detection assay needs venom specific antibodies (VSAbs) for that monovalent antisera was prepared by hyperimmunization of rabbits with specific venom. However, obtained antibodies exhibit maximum activity towards homologous venom as well as quantifiable degree of cross-reactivity with heterologous venoms. Use of these antibodies for development of selective envenomation detection assay may create ambiguity in results, therefore needs to isolate VSAbs from monovalent antisera. The cross-reacting antibodies were specifically removed by immunoaffinity chromatography to obtain VSAbs. For the development of venom detection ELISA test (VDET), two different species of antibodies were used that offers enhanced sensitivity along with selective identification of the venoms of the responsible snakes. In conclusion, the developed VDET is rapid, specific, yet sensitive to detect venoms of offending snake species, and its venom concentration down to 1.0 ng/ml. However, the device observed with lowest venom concentration detection ability in the range <1.0 ng/ml from experimentally envenomated samples. The implementation of VDET will help in avoiding unnecessary usage and adverse reactions of snake antivenin. The test has all the

  15. Electrophoretic Characterization of Elapid, Viperid and Crotalid Snake Venoms

    DTIC Science & Technology

    1989-08-01

    and patent rights’. UNCLASSIFIED UNCLASSIFIED ABSTRACT This report deals with comparative studies of snake venoms from 21 species representing Elapidae ...Blue Stains Figure 4 shows a pair of typical non-SDS electropherograms of native venom proteins from representative species of Elapidae , Viperidae and...SOURCES OF THE SNAKE VENOMS STUDIED VENOM SPECIES COMMON NAME NO. Elapidae : 14. Naja melanoleuca black cobra 15. 9-ja haje Egyptian cobra 16. Naja naja

  16. Tityus serrulatus venom--A lethal cocktail.

    PubMed

    Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro Junior, Ernesto Lopes; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Cordeiro, Francielle Almeida; Longhim, Heloisa Tavoni; Cremonez, Caroline Marroni; Oliveira, Guilherme Honda; Arantes, Eliane Candiani

    2015-12-15

    Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic peptide, proteins with high molecular mass, peptides, free amino acids and neurotoxins. Neurotoxins are considered the most responsible for the envenoming syndrome due to their pharmacological action on ion channels such as voltage-gated sodium (Nav) and potassium (Kv) channels. The major goal of this review is to present important advances in Ts envenoming research, correlating both the crude Ts venom and isolated toxins with alterations observed in all human systems. The most remarkable event lies in the Ts induced massive releasing of neurotransmitters influencing, directly or indirectly, the entire body. Ts venom proved to extremely affect nervous and muscular systems, to modulate the immune system, to induce cardiac disorders, to cause pulmonary edema, to decrease urinary flow and to alter endocrine, exocrine, reproductive, integumentary, skeletal and digestive functions. Therefore, Ts venom possesses toxins affecting all anatomic systems, making it a lethal cocktail. However, its low lethality may be due to the low venom mass injected, to the different venom compositions, the body characteristics and health conditions of the victim and the local of Ts sting. Furthermore, we also described the different treatments employed during envenoming cases. In particular, throughout the review, an effort will be made to provide information from an extensive documented studies concerning Ts venom in vitro, in animals and in humans (a total of 151 references). Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Studies on the Biology, Venom and Ultrastructure of Selected Venomous Fishes, Including the Scorpionfishes and Stingrays.

    DTIC Science & Technology

    1980-04-25

    and venous pressures; respirations ; and blood pH, P02 , PC0 2 and hematocrit; and total serum protein. The results indicated a fairly consistent...by the jellyfish Pelagia noctiluca in the Adriatic. -------. ... . Abstract of the 6th International Symposium on Animal, Plant and Microbial Toxins...designed to study hypotension was employed to measure arterial and venous pressures/’ respirations ; and blood pH, P02, PC02 and hematocrit; and total

  18. Immunoreactivity between venoms and commercial antiserums in four Chinese snakes and venom identification by species-specific antibody.

    PubMed

    Gao, Jian-Fang; Wang, Jin; Qu, Yan-Fu; Ma, Xiao-Mei; Ji, Xiang

    2013-01-31

    We studied the immunoreactivity between venoms and commercial antiserums in four Chinese venomous snakes, Bungarus multicinctus, Naja atra, Deinagkistrodon acutus and Gloydius brevicaudus. Venoms from the four snakes shared common antigenic components, and most venom components expressed antigenicity in the immunological reaction between venoms and antiserums. Antiserums cross-reacted with heterologous venoms. Homologous venom and antiserum expressed the highest reaction activity in all cross-reactions. Species-specific antibodies (SSAbs) were obtained from four antiserums by immunoaffinity chromatography: the whole antiserum against each species was gradually passed through a medium system coated with heterologous venoms, and the cross-reacting components in antiserum were immunoabsorbed by the common antigens in heterologous venoms; the unbound components (i.e., SSAbs) were collected, and passed through Hitrap G protein column and concentrated. The SSAbs were found to have high specificity by western blot and enzyme-linked immunosorbent assay (ELISA). A 6-well ELISA strip coated with SSAbs was used to assign a venom sample and blood and urine samples from the envenomed rats to a given snake species. Our detections could differentiate positive and negative samples, and identify venoms of a snake species in about 35 min. The ELISA strips developed in this study are clinically useful in rapid and reliable identification of venoms from the above four snake species.

  19. Comparative venom gland transcriptome analysis of the scorpion Lychas mucronatus reveals intraspecific toxic gene diversity and new venomous components.

    PubMed

    Ruiming, Zhao; Yibao, Ma; Yawen, He; Zhiyong, Di; Yingliang, Wu; Zhijian, Cao; Wenxin, Li

    2010-07-28

    Lychas mucronatus is one scorpion species widely distributed in Southeast Asia and southern China. Anything is hardly known about its venom components, despite the fact that it can often cause human accidents. In this work, we performed a venomous gland transcriptome analysis by constructing and screening the venom gland cDNA library of the scorpion Lychas mucronatus from Yunnan province and compared it with the previous results of Hainan-sourced Lychas mucronatus. A total of sixteen known types of venom peptides and proteins are obtained from the venom gland cDNA library of Yunnan-sourced Lychas mucronatus, which greatly increase the number of currently reported scorpion venom peptides. Interestingly, we also identified nineteen atypical types of venom molecules seldom reported in scorpion species. Surprisingly, the comparative transcriptome analysis of Yunnan-sourced Lychas mucronatus and Hainan-sourced Lychas mucronatus indicated that enormous diversity and vastly abundant difference could be found in venom peptides and proteins between populations of the scorpion Lychas mucronatus from different geographical regions. This work characterizes a large number of venom molecules never identified in scorpion species. This result provides a comparative analysis of venom transcriptomes of the scorpion Lychas mucronatus from different geographical regions, which thoroughly reveals the fact that the venom peptides and proteins of the same scorpion species from different geographical regions are highly diversified and scorpion evolves to adapt a new environment by altering the primary structure and abundance of venom peptides and proteins.

  20. Comparative venom gland transcriptome analysis of the scorpion Lychas mucronatus reveals intraspecific toxic gene diversity and new venomous components

    PubMed Central

    2010-01-01

    Background Lychas mucronatus is one scorpion species widely distributed in Southeast Asia and southern China. Anything is hardly known about its venom components, despite the fact that it can often cause human accidents. In this work, we performed a venomous gland transcriptome analysis by constructing and screening the venom gland cDNA library of the scorpion Lychas mucronatus from Yunnan province and compared it with the previous results of Hainan-sourced Lychas mucronatus. Results A total of sixteen known types of venom peptides and proteins are obtained from the venom gland cDNA library of Yunnan-sourced Lychas mucronatus, which greatly increase the number of currently reported scorpion venom peptides. Interestingly, we also identified nineteen atypical types of venom molecules seldom reported in scorpion species. Surprisingly, the comparative transcriptome analysis of Yunnan-sourced Lychas mucronatus and Hainan-sourced Lychas mucronatus indicated that enormous diversity and vastly abundant difference could be found in venom peptides and proteins between populations of the scorpion Lychas mucronatus from different geographical regions. Conclusions This work characterizes a large number of venom molecules never identified in scorpion species. This result provides a comparative analysis of venom transcriptomes of the scorpion Lychas mucronatus from different geographical regions, which thoroughly reveals the fact that the venom peptides and proteins of the same scorpion species from different geographical regions are highly diversified and scorpion evolves to adapt a new environment by altering the primary structure and abundance of venom peptides and proteins. PMID:20663230

  1. Venom proteomic and venomous glands transcriptomic analysis of the Egyptian scorpion Scorpio maurus palmatus (Arachnida: Scorpionidae).

    PubMed

    Abdel-Rahman, Mohamed A; Quintero-Hernandez, Veronica; Possani, Lourival D

    2013-11-01

    Proteomic analysis of the scorpion venom Scorpio maurus palmatus was performed using reverse-phase HPLC separation followed by mass spectrometry determination. Sixty five components were identified with molecular masses varying from 413 to 14,009 Da. The high percentage of peptides (41.5%) was from 3 to 5 KDa which may represent linear antimicrobial peptides and KScTxs. Also, 155 expressed sequence tags (ESTs) were analyzed through construction the cDNA library prepared from a pair of venomous gland. About 77% of the ESTs correspond to toxin-like peptides and proteins with definite open reading frames. The cDNA sequencing results also show the presence of sequences whose putative products have sequence similarity with antimicrobial peptides (24%), insecticidal toxins, β-NaScTxs, κ-KScTxs, α-KScTxs, calcines and La1-like peptides. Also, we have obtained 23 atypical types of venom molecules not recorded in other scorpion species. Moreover, 9% of the total ESTs revealed significant similarities with proteins involved in the cellular processes of these scorpion venomous glands. This is the first set of molecular masses and transcripts described from this species, in which various venom molecules have been identified. They belong to either known or unassigned types of scorpion venom peptides and proteins, and provide valuable information for evolutionary analysis and venomics.

  2. A study on the venom yield of venomous snake species from Argentina.

    PubMed

    de Roodt, A R; Dolab, J A; Galarce, P P; Gould, E; Litwin, S; Dokmetjian, J C; Segre, L; Vidal, J C

    1998-12-01

    A study on the venom yield of snakes from Argentina over a three year period was carried out on adult specimens of Bothrops alternatus (n = 74); Bothrops neuwiedii (n = 127); Bothrops ammodytoides (n = 30); Bothrops moojeni (n = 14); Bothrops jararaca (n = 14); B. jararacussu (n = 6); Crotalus durissus terrificus (n = 120) and Micrurus spp. (n = 6) as well as with 12 specimens of newborn C. d. terrificus kept in captivity. While for each species there was a positive correlation between venom yield and number of snakes milked, the correlation with the snake's body weights after individual milkings was even better, suggesting that the size of the snakes is more important in determining the venom yield than the number of snakes milked or the specimen's sex. Individual milkings indicated that, in addition to the snake size, when the amount of venom is normalized per 100 g body weight there is a species specific difference in venom yield. It follows the order B. jararacussu > B. moojeni approximately = B. jararaca approximately = B. alternatus > B. neuwiedii> Micrurus spp approximately = B. ammodytoides> C. d. terrificus. Although the venom yield per 100 g body weight of newborn C. d. terrificus specimens is 2-fold higher than that of adults, no correlation was observed between venom yield and body weight.

  3. Proteome analysis of brown spider venom: identification of loxnecrogin isoforms in Loxosceles gaucho venom.

    PubMed

    Machado, Leandro F; Laugesen, Sabrina; Botelho, Elvio D; Ricart, Carlos A O; Fontes, Wagner; Barbaro, Katia C; Roepstorff, Peter; Sousa, Marcelo V

    2005-05-01

    Brown spiders of the Loxosceles genus are distributed worldwide. In Brazil, eight species are found in Southern states, where the envenomation by Loxosceles venom (loxoscelism) is a health problem. The mechanism of the dermonecrotic action of Loxosceles venom is not totally understood. Two isoforms of dermonecrotic toxins (loxnecrogins) from L. gaucho venom have been previously purified, and showed sequence similarities to sphingomyelinase. Herein we employed a proteomic approach to obtain a global view of the venom proteome, with a particular interest in the loxnecrogin isoforms' pattern. Proteomic two-dimensional gel electrophoresis maps for L. gaucho, L. intermedia, and L. laeta venoms showed a major protein region (30-35 kDa, pI 3-10), where at least eight loxnecrogin isoforms could be separated and identified. Their characterization used a combined approach composed of Edman chemical sequencing, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and electrospray ionization-quadropole-time of flight tandem mass spectrometry leading to the identification of sphingomyelinases D. The venom was also pre-fractionated by gel filtration on a Superose 12 fast protein liqiud chromatography column, followed by capillary liquid chromatography-mass spectrometry. Eleven possible loxnecrogin isoforms around 30-32 kDa were detected. The identification of dermonecrotic toxin isoforms in L. gaucho venom is an important step towards understanding the physiopathology of the envenomation, leading to improvements in the immunotherapy of loxoscelism.

  4. Antinociceptive properties of Micrurus lemniscatus venom.

    PubMed

    Leite dos Santos, Gisele Graça; Casais e Silva, Luciana Lyra; Pereira Soares, Milena Botelho; Villarreal, Cristiane Flora

    2012-11-01

    The therapeutic potential of snake venoms for pain control has been previously demonstrated. In the present study, the antinociceptive effects of Micrurus lemniscatus venom (MlV) were investigated in experimental models of pain. The antinociceptive activity of MIV was evaluated using the writhing, formalin, and tail flick tests. Mice motor performance was assessed in the rota rod and open field tests. In a screening test for new antinociceptive substances--the writhing test--oral administration of MlV (19.7-1600 μg/kg) produced significant antinociceptive effect. The venom (1600 μg/kg) also inhibited both phases of the formalin test, confirming the antinociceptive activity. The administration of MlV (1600 μg/kg) did not cause motor impairment in the rota rod and open field tests, which excluded possible non-specific muscle relaxant or sedative effects of the venom. The MIV (177-1600 μg/kg) also increases the tail flick latency response, indicating a central antinociceptive effect for the venom. In this test, the MlV-induced antinociceptive effect was long-lasting and higher than that of morphine, an analgesic considered the gold standard. In another set of experiments, the mechanisms involved in the venom-induced antinociception were investigated through the use of pharmacological antagonists. The MlV (1600 μg/kg) antinociceptive effect was prevented by naloxone (5 mg/kg), a non-selective opioid receptor antagonist, suggesting that this effect is mediated by activation of opioid receptors. In addition, the pre-treatment with the μ-opioid receptor antagonist CTOP (1 mg/kg) blocked the venom antinociceptive effect, while the k-opioid receptor antagonist nor-BNI (0.5 mg/kg) or the δ-opioid receptor antagonist naltrindole (3 mg/kg) only partially reduced the venom-induced antinociception. The present study demonstrates, for the first time, that oral administration of M. lemniscatus venom, at doses that did not induce any motor performance alteration, produced

  5. Scorpion Venom and the Inflammatory Response

    PubMed Central

    Petricevich, Vera L.

    2010-01-01

    Scorpion venoms consist of a complex of several toxins that exhibit a wide range of biological properties and actions, as well as chemical compositions, toxicity, and pharmacokinetic and pharmacodynamic characteristics. These venoms are associated with high morbility and mortality, especially among children. Victims of envenoming by a scorpion suffer a variety of pathologies, involving mainly both sympathetic and parasympathetic stimulation as well as central manifestations such as irritability, hyperthermia, vomiting, profuse salivation, tremor, and convulsion. The clinical signs and symptoms observed in humans and experimental animals are related with an excessive systemic host inflammatory response to stings and stings, respectively. Although the pathophysiology of envenomation is complex and not yet fully understood, venom and immune responses are known to trigger the release of inflammatory mediators that are largely mediated by cytokines. In models of severe systemic inflammation produced by injection of high doses of venom or venoms products, the increase in production of proinflammatory cytokines significantly contributes to immunological imbalance, multiple organ dysfunction and death. The cytokines initiate a cascade of events that lead to illness behaviors such as fever, anorexia, and also physiological events in the host such as activation of vasodilatation, hypotension, and increased of vessel permeability. PMID:20300540

  6. Biochemical characterization of the Micrurus pyrrhocryptus venom.

    PubMed

    Dokmetjian, José Christian; Del Canto, Sergio; Vinzón, Sabrina; de Jiménez Bonino, Mirtha Biscoglio

    2009-03-01

    Snake venom toxicity is the consequence of a combination of peptides and proteins whose identification and characterization are of great importance to understand envenomation and develop new clinical treatments. The Elapinae subfamily includes coral snakes whose bite causes mainly neurotoxic effects which disable muscle contraction and paralyse the heart as well as inhibit respiration. However, the structure-function relationship of venom toxins has been investigated only for a few species. We herein study biological aspects of the Micrurus pyrrhocryptus venom such as LD(50), hemorrhagic, necrotic, coagulant, myotoxic and hemolytic activity as well as the ability of venom components to compete with alpha-Bungarotoxin for the ligand-binding site of the nicotinic acetylcholine receptor. Besides, we report the determination of the molecular mass and N-terminal sequence of toxins including PLA2s, short, long and weak neurotoxins. The complete sequence of one of the short neurotoxins has also been obtained, this being the first sequence of an alpha-neurotoxin determined in the M. pyrrhocryptus venom and one of the few fully determined in members of the Micrurus genus.

  7. [Allergy to hymenoptera venoms in children].

    PubMed

    Rancé, F; Abbal, M; Brémont, F; Dutau, G

    1999-01-01

    Incidence of hymenoptera venom allergy in children is about 0.4 to 0.8%. Clinical features usually range from urticaria to anaphylaxis. Fatal reactions can occur but with less frequency than in adults. Allergologic investigations must be performed in children with systemic or generalized reactions after hymenoptera stings, which may lead to venom immunotherapy. Venom immunotherapy is well reported, but protocols differ according to the authors: ultra-rush in 3 h, accelerated in 3 to 5 days and semi-rush in 2 to 8 weeks. Results are always excellent (90 to 100%). We report our experience with 91 children receiving venom immunotherapy. Clinical history and positivity of skin tests indicated immunotherapy. Clinical symptoms were anaphylaxis (15.3%), serious reaction (37.3%) strong reaction (34%), and mild reaction (7.6%). Changes in immunological parameters revealed wide individual variations, not differing from data in the literature, with no correlation with evolution of immunotherapy. Venom immunotherapy appeared with good tolerability in children, whatever the protocol used.

  8. Mast Cells Can Enhance Resistance to Snake and Honeybee Venoms

    NASA Astrophysics Data System (ADS)

    Metz, Martin; Piliponsky, Adrian M.; Chen, Ching-Cheng; Lammel, Verena; Åbrink, Magnus; Pejler, Gunnar; Tsai, Mindy; Galli, Stephen J.

    2006-07-01

    Snake or honeybee envenomation can cause substantial morbidity and mortality, and it has been proposed that the activation of mast cells by snake or insect venoms can contribute to these effects. We show, in contrast, that mast cells can significantly reduce snake-venom-induced pathology in mice, at least in part by releasing carboxypeptidase A and possibly other proteases, which can degrade venom components. Mast cells also significantly reduced the morbidity and mortality induced by honeybee venom. These findings identify a new biological function for mast cells in enhancing resistance to the morbidity and mortality induced by animal venoms.

  9. Components of Asobara venoms and their effects on hosts.

    PubMed

    Moreau, Sébastien J M; Vinchon, Sophie; Cherqui, Anas; Prévost, Geneviève

    2009-01-01

    Hymenoptera of the Asobara genus are endophagous parasitoids of Drosophila larvae. In these apocrita insects whose venom gland is associated with the female reproductive tract, the wasp venom is injected into the host along with the parasitoid egg during oviposition. We conducted a comparative study of the venom apparatuses from three Asobara spp.: the European Asobara tabida, the Asiatic A. japonica and the African A. citri. Light and electron microscopy of venom glands, together with the biochemical analysis of their contents, revealed important differences between Asobara spp. In addition, the physiological effects of female wasp's venom injected into Drosophila larvae differed greatly between the tested Asobara spp.

  10. Use of immunoturbidimetry to detect venom-antivenom binding using snake venoms.

    PubMed

    O'Leary, M A; Maduwage, K; Isbister, G K

    2013-01-01

    Immunoturbidimetry studies the phenomenon of immunoprecipitation of antigens and antibodies in solution, where there is the formation of large, polymeric insoluble immunocomplexes that increase the turbidity of the solution. We used immunoturbidimetry to investigate the interaction between commercial snake antivenoms and snake venoms, as well as cross-reactivity between different snake venoms. Serial dilutions of commercial snake antivenoms (100μl) in water were placed in the wells of a microtitre plate and 100μl of a venom solution (50μg/ml in water) was added. Absorbance readings were taken at 340nm every minute on a BioTek ELx808 plate reader at 37°C. Limits imposed were a 30minute cut-off and 0.004 as the lowest significant maximum increase. Reactions with rabbit antibodies were carried out similarly, except that antibody dilutions were in PBS. Mixing venom and antivenom/antibodies resulted in an immediate increase in turbidity, which either reached a maximum or continued to increase until a 30minute cut-off. There was a peak in absorbance readings for most Australian snake venoms mixed with the corresponding commercial antivenom, except for Pseudonaja textilis venom and brown snake antivenom. There was cross-reactivity between Naja naja venom from Sri Lanka and tiger snake antivenom indicated by turbidity when they were mixed. Mixing rabbit anti-snake antibodies with snake venoms resulted in increasing turbidity, but there was not a peak suggesting the antibodies were not sufficiently concentrated. The absorbance reading at pre-determined concentrations of rabbit antibodies mixed with different venoms was able to quantify the cross-reactivity between venoms. Indian antivenoms from two manufacturers were tested against four Sri Lankan snake venoms (Daboia russelli, N. naja, Echis carinatus and Bungarus caeruleus) and showed limited formation of immunocomplexes with antivenom from one manufacturer. The turbidity test provides an easy and rapid way to compare

  11. Combined snake venomics and venom gland transcriptomic analysis of the ocellated carpet viper, Echis ocellatus.

    PubMed

    Wagstaff, Simon C; Sanz, Libia; Juárez, Paula; Harrison, Robert A; Calvete, Juan J

    2009-01-30

    Snakebite in Africa causes thousands of deaths annually and considerable permanent physical disability. The saw-scaled viper, Echis ocellatus, represents the single most medically important snake species in West Africa. To provide a detailed compositional analysis of the venom of E. ocellatus for designing novel toxin-specific immunotherapy and to delineate sequence structure-function relationships of individual toxins, we characterised the venom proteome and the venom gland transcriptome. Whole E. ocellatus venom was fractionated by reverse-phase HPLC, followed by analysis of each chromatographic fraction using a combination of SDS-PAGE, N-terminal sequencing, MALDI-TOF mass fingerprinting, and CID-MS/MS of tryptic peptides. This analysis identified around 35 distinct proteins of molecular masses in the range of 5.5-110 kDa belonging to 8 different toxin families (disintegrin, DC-fragment, phospholipase A(2), cysteine-rich secretory protein, serine proteinase, C-type lectin, l-amino acid oxidase, and Zn(2+)-dependent metalloprotease). Comparison of the toxin composition of E. ocellatus venom determined using a proteomic approach, with the predicted proteome derived from assembly of 1000 EST sequences from a E. ocellatus venom gland cDNA library, shows some differences. Most notably, peptides derived from 26% of the venom proteins could not be ascribed an exact match in the transcriptome. Similarly, 64 (67%) out of the 95 putative toxin clusters reported in the transcriptome did not match to peptides detected in the venom proteome. These data suggest that the final composition of venom is influenced by transcriptional and post-translational mechanisms that may be more complex than previously appreciated. This, in turn, emphasises the value of combining proteomic and transcriptomic approaches to acquire a more complete understanding of the precise composition of snake venom, than would be gleaned from using one analysis alone. From a clinical perspective, the large

  12. Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

    PubMed Central

    Aird, Steven D.; da Silva, Nelson Jorge; Qiu, Lijun; Villar-Briones, Alejandro; Saddi, Vera Aparecida; Pires de Campos Telles, Mariana; Grau, Miguel L.; Mikheyev, Alexander S.

    2017-01-01

    Venom gland transcriptomes and proteomes of six Micrurus taxa (M. corallinus, M. lemniscatus carvalhoi, M. lemniscatus lemniscatus, M. paraensis, M. spixii spixii, and M. surinamensis) were investigated, providing the most comprehensive, quantitative data on Micrurus venom composition to date, and more than tripling the number of Micrurus venom protein sequences previously available. The six venomes differ dramatically. All are dominated by 2–6 toxin classes that account for 91–99% of the toxin transcripts. The M. s. spixii venome is compositionally the simplest. In it, three-finger toxins (3FTxs) and phospholipases A2 (PLA2s) comprise >99% of the toxin transcripts, which include only four additional toxin families at levels ≥0.1%. Micrurus l. lemniscatus venom is the most complex, with at least 17 toxin families. However, in each venome, multiple structural subclasses of 3FTXs and PLA2s are present. These almost certainly differ in pharmacology as well. All venoms also contain phospholipase B and vascular endothelial growth factors. Minor components (0.1–2.0%) are found in all venoms except that of M. s. spixii. Other toxin families are present in all six venoms at trace levels (<0.005%). Minor and trace venom components differ in each venom. Numerous novel toxin chemistries include 3FTxs with previously unknown 8- and 10-cysteine arrangements, resulting in new 3D structures and target specificities. 9-cysteine toxins raise the possibility of covalent, homodimeric 3FTxs or heterodimeric toxins with unknown pharmacologies. Probable muscarinic sequences may be reptile-specific homologs that promote hypotension via vascular mAChRs. The first complete sequences are presented for 3FTxs putatively responsible for liberating glutamate from rat brain synaptosomes. Micrurus C-type lectin-like proteins may have 6–9 cysteine residues and may be monomers, or homo- or heterodimers of unknown pharmacology. Novel KSPIs, 3× longer than any seen previously, appear to

  13. Full-Length Venom Protein cDNA Sequences from Venom-Derived mRNA: Exploring Compositional Variation and Adaptive Multigene Evolution.

    PubMed

    Modahl, Cassandra M; Mackessy, Stephen P

    2016-06-01

    Envenomation of humans by snakes is a complex and continuously evolving medical emergency, and treatment is made that much more difficult by the diverse biochemical composition of many venoms. Venomous snakes and their venoms also provide models for the study of molecular evolutionary processes leading to adaptation and genotype-phenotype relationships. To compare venom complexity and protein sequences, venom gland transcriptomes are assembled, which usually requires the sacrifice of snakes for tissue. However, toxin transcripts are also present in venoms, offering the possibility of obtaining cDNA sequences directly from venom. This study provides evidence that unknown full-length venom protein transcripts can be obtained from the venoms of multiple species from all major venomous snake families. These unknown venom protein cDNAs are obtained by the use of primers designed from conserved signal peptide sequences within each venom protein superfamily. This technique was used to assemble a partial venom gland transcriptome for the Middle American Rattlesnake (Crotalus simus tzabcan) by amplifying sequences for phospholipases A2, serine proteases, C-lectins, and metalloproteinases from within venom. Phospholipase A2 sequences were also recovered from the venoms of several rattlesnakes and an elapid snake (Pseudechis porphyriacus), and three-finger toxin sequences were recovered from multiple rear-fanged snake species, demonstrating that the three major clades of advanced snakes (Elapidae, Viperidae, Colubridae) have stable mRNA present in their venoms. These cDNA sequences from venom were then used to explore potential activities derived from protein sequence similarities and evolutionary histories within these large multigene superfamilies. Venom-derived sequences can also be used to aid in characterizing venoms that lack proteomic profiles and identify sequence characteristics indicating specific envenomation profiles. This approach, requiring only venom, provides

  14. Full-Length Venom Protein cDNA Sequences from Venom-Derived mRNA: Exploring Compositional Variation and Adaptive Multigene Evolution

    PubMed Central

    Modahl, Cassandra M.; Mackessy, Stephen P.

    2016-01-01

    Envenomation of humans by snakes is a complex and continuously evolving medical emergency, and treatment is made that much more difficult by the diverse biochemical composition of many venoms. Venomous snakes and their venoms also provide models for the study of molecular evolutionary processes leading to adaptation and genotype-phenotype relationships. To compare venom complexity and protein sequences, venom gland transcriptomes are assembled, which usually requires the sacrifice of snakes for tissue. However, toxin transcripts are also present in venoms, offering the possibility of obtaining cDNA sequences directly from venom. This study provides evidence that unknown full-length venom protein transcripts can be obtained from the venoms of multiple species from all major venomous snake families. These unknown venom protein cDNAs are obtained by the use of primers designed from conserved signal peptide sequences within each venom protein superfamily. This technique was used to assemble a partial venom gland transcriptome for the Middle American Rattlesnake (Crotalus simus tzabcan) by amplifying sequences for phospholipases A2, serine proteases, C-lectins, and metalloproteinases from within venom. Phospholipase A2 sequences were also recovered from the venoms of several rattlesnakes and an elapid snake (Pseudechis porphyriacus), and three-finger toxin sequences were recovered from multiple rear-fanged snake species, demonstrating that the three major clades of advanced snakes (Elapidae, Viperidae, Colubridae) have stable mRNA present in their venoms. These cDNA sequences from venom were then used to explore potential activities derived from protein sequence similarities and evolutionary histories within these large multigene superfamilies. Venom-derived sequences can also be used to aid in characterizing venoms that lack proteomic profiles and identify sequence characteristics indicating specific envenomation profiles. This approach, requiring only venom, provides

  15. Fibrin(ogen)olytic activity of bumblebee venom serine protease

    SciTech Connect

    Qiu Yuling; Choo, Young Moo; Yoon, Hyung Joo; Jia Jingming; Cui Zheng; Wang Dong; Kim, Doh Hoon; Sohn, Hung Dae; Jin, Byung Rae

    2011-09-01

    Bee venom is a rich source of pharmacologically active components; it has been used as an immunotherapy to treat bee venom hypersensitivity, and venom therapy has been applied as an alternative medicine. Here, we present evidence that the serine protease found in bumblebee venom exhibits fibrin(ogen)olytic activity. Compared to honeybee venom, bumblebee venom contains a higher content of serine protease, which is one of its major components. Venom serine proteases from bumblebees did not cross-react with antibodies against the honeybee venom serine protease. We provide functional evidence indicating that bumblebee (Bombus terrestris) venom serine protease (Bt-VSP) acts as a fibrin(ogen)olytic enzyme. Bt-VSP activates prothrombin and directly degrades fibrinogen into fibrin degradation products. However, Bt-VSP is not a plasminogen activator, and its fibrinolytic activity is less than that of plasmin. Taken together, our results define roles for Bt-VSP as a prothrombin activator, a thrombin-like protease, and a plasmin-like protease. These findings offer significant insight into the allergic reaction sequence that is initiated by bee venom serine protease and its potential usefulness as a clinical agent in the field of hemostasis and thrombosis. - Graphical abstract: Display Omitted Highlights: > Bumblebee venom serine protease (Bt-VSP) is a fibrin(ogen)olytic enzyme. > Bt-VSP activates prothrombin. > Bt-VSP directly degrades fibrinogen into fibrin degradation products. > Bt-VSP is a hemostatically active protein that is a potent clinical agent.

  16. Centipede venoms and their components: resources for potential therapeutic applications.

    PubMed

    Hakim, Md Abdul; Yang, Shilong; Lai, Ren

    2015-11-17

    Venomous animals have evolved with sophisticated bio-chemical strategies to arrest prey and defend themselves from natural predators. In recent years, peptide toxins from venomous animals have drawn considerable attention from researchers due to their surprising chemical, biochemical, and pharmacological diversity. Similar to other venomous animals, centipedes are one of the crucial venomous arthropods that have been used in traditional medicine for hundreds of years in China. Despite signifying pharmacological importance, very little is known about the active components of centipede venoms. More than 500 peptide sequences have been reported in centipede venomous glands by transcriptome analysis, but only a small number of peptide toxins from centipede has been functionally described. Like other venomous animals such as snakes, scorpions, and spiders, the venom of centipedes could be an excellent source of peptides for developing drugs for treatments as well as bio-insecticides for agrochemical applications. Although centipede venoms are yet to be adequately studied, the venom of centipedes as well as their components described to date, should be compiled to help further research. Therefore, based on previous reports, this review focusses on findings and possible therapeutic applications of centipede venoms as well as their components.

  17. Centipede Venoms and Their Components: Resources for Potential Therapeutic Applications

    PubMed Central

    Hakim, Md Abdul; Yang, Shilong; Lai, Ren

    2015-01-01

    Venomous animals have evolved with sophisticated bio-chemical strategies to arrest prey and defend themselves from natural predators. In recent years, peptide toxins from venomous animals have drawn considerable attention from researchers due to their surprising chemical, biochemical, and pharmacological diversity. Similar to other venomous animals, centipedes are one of the crucial venomous arthropods that have been used in traditional medicine for hundreds of years in China. Despite signifying pharmacological importance, very little is known about the active components of centipede venoms. More than 500 peptide sequences have been reported in centipede venomous glands by transcriptome analysis, but only a small number of peptide toxins from centipede has been functionally described. Like other venomous animals such as snakes, scorpions, and spiders, the venom of centipedes could be an excellent source of peptides for developing drugs for treatments as well as bio-insecticides for agrochemical applications. Although centipede venoms are yet to be adequately studied, the venom of centipedes as well as their components described to date, should be compiled to help further research. Therefore, based on previous reports, this review focusses on findings and possible therapeutic applications of centipede venoms as well as their components. PMID:26593947

  18. Tracing Monotreme Venom Evolution in the Genomics Era

    PubMed Central

    Whittington, Camilla M.; Belov, Katherine

    2014-01-01

    The monotremes (platypuses and echidnas) represent one of only four extant venomous mammalian lineages. Until recently, monotreme venom was poorly understood. However, the availability of the platypus genome and increasingly sophisticated genomic tools has allowed us to characterize platypus toxins, and provides a means of reconstructing the evolutionary history of monotreme venom. Here we review the physiology of platypus and echidna crural (venom) systems as well as pharmacological and genomic studies of monotreme toxins. Further, we synthesize current ideas about the evolution of the venom system, which in the platypus is likely to have been retained from a venomous ancestor, whilst being lost in the echidnas. We also outline several research directions and outstanding questions that would be productive to address in future research. An improved characterization of mammalian venoms will not only yield new toxins with potential therapeutic uses, but will also aid in our understanding of the way that this unusual trait evolves. PMID:24699339

  19. The humoral immune response induced by snake venom toxins.

    PubMed

    da Silva, Wilmar Dias; Tambourgi, Denise V

    2011-10-01

    This review summarizes the key contributions to our knowledge regarding the immune response induced by snake venom toxins, focusing particularly on the production of antibodies and their venom-neutralizing effects. We cover the past and present state of the art of anti-snake venom production, followed by an overview of the venomous snakes and their venoms. The toxic properties of relevant snake venom toxins are approached in some details, with particular emphasis on the molecular domains responsible for binding to cells or plasma components in victims. The interactions of these domains are also reviewed, particularly the putatively relevant epitopes, along with the immune system and the resulting antibodies. We also review trials aimed at reducing the quantities of non-relevant antibodies in the antivenoms by substituting whole venoms with purified toxins to immunize animals, or the immunogenicity of the heterologous antivenom antibodies by humanizing their molecules.

  20. Tracing monotreme venom evolution in the genomics era.

    PubMed

    Whittington, Camilla M; Belov, Katherine

    2014-04-02

    The monotremes (platypuses and echidnas) represent one of only four extant venomous mammalian lineages. Until recently, monotreme venom was poorly understood. However, the availability of the platypus genome and increasingly sophisticated genomic tools has allowed us to characterize platypus toxins, and provides a means of reconstructing the evolutionary history of monotreme venom. Here we review the physiology of platypus and echidna crural (venom) systems as well as pharmacological and genomic studies of monotreme toxins. Further, we synthesize current ideas about the evolution of the venom system, which in the platypus is likely to have been retained from a venomous ancestor, whilst being lost in the echidnas. We also outline several research directions and outstanding questions that would be productive to address in future research. An improved characterization of mammalian venoms will not only yield new toxins with potential therapeutic uses, but will also aid in our understanding of the way that this unusual trait evolves.

  1. Studies on sea snake venom

    PubMed Central

    TAMIYA, Nobuo; YAGI, Tatsuhiko

    2011-01-01

    Erabutoxins a and b are neurotoxins isolated from venom of a sea snake Laticauda semifasciata (erabu-umihebi). Amino acid sequences of the toxins indicated that the toxins are members of a superfamily consisting of short and long neurotoxins and cytotoxins found in sea snakes and terrestrial snakes. The short neurotoxins to which erabutoxins belong act by blocking the nicotinic acetylcholine receptor on the post synaptic membrane in a manner similar to that of curare. X-ray crystallography and NMR analyses showed that the toxins have a three-finger structure, in which three fingers made of three loops emerging from a dense core make a gently concave surface of the protein. The sequence comparison and the location of essential residues on the protein suggested the mechanism of binding of the toxin to the acetylcholine receptor. Classification of snakes by means of sequence comparison and that based on different morphological features were inconsistent, which led the authors to propose a hypothesis “Evolution without divergence.” PMID:21422738

  2. Studies on sea snake venom.

    PubMed

    Tamiya, Nobuo; Yagi, Tatsuhiko

    2011-01-01

    Erabutoxins a and b are neurotoxins isolated from venom of a sea snake Laticauda semifasciata (erabu-umihebi). Amino acid sequences of the toxins indicated that the toxins are members of a superfamily consisting of short and long neurotoxins and cytotoxins found in sea snakes and terrestrial snakes. The short neurotoxins to which erabutoxins belong act by blocking the nicotinic acetylcholine receptor on the post synaptic membrane in a manner similar to that of curare. X-ray crystallography and NMR analyses showed that the toxins have a three-finger structure, in which three fingers made of three loops emerging from a dense core make a gently concave surface of the protein. The sequence comparison and the location of essential residues on the protein suggested the mechanism of binding of the toxin to the acetylcholine receptor. Classification of snakes by means of sequence comparison and that based on different morphological features were inconsistent, which led the authors to propose a hypothesis "Evolution without divergence."

  3. The first venomous crustacean revealed by transcriptomics and functional morphology: remipede venom glands express a unique toxin cocktail dominated by enzymes and a neurotoxin.

    PubMed

    von Reumont, Björn M; Blanke, Alexander; Richter, Sandy; Alvarez, Fernando; Bleidorn, Christoph; Jenner, Ronald A

    2014-01-01

    Animal venoms have evolved many times. Venomous species are especially common in three of the four main groups of arthropods (Chelicerata, Myriapoda, and Hexapoda), which together represent tens of thousands of species of venomous spiders, scorpions, centipedes, and hymenopterans. Surprisingly, despite their great diversity of body plans, there is no unambiguous evidence that any crustacean is venomous. We provide the first conclusive evidence that the aquatic, blind, and cave-dwelling remipede crustaceans are venomous and that venoms evolved in all four major arthropod groups. We produced a three-dimensional reconstruction of the venom delivery apparatus of the remipede Speleonectes tulumensis, showing that remipedes can inject venom in a controlled manner. A transcriptomic profile of its venom glands shows that they express a unique cocktail of transcripts coding for known venom toxins, including a diversity of enzymes and a probable paralytic neurotoxin very similar to one described from spider venom. We screened a transcriptomic library obtained from whole animals and identified a nontoxin paralog of the remipede neurotoxin that is not expressed in the venom glands. This allowed us to reconstruct its probable evolutionary origin and underlines the importance of incorporating data derived from nonvenom gland tissue to elucidate the evolution of candidate venom proteins. This first glimpse into the venom of a crustacean and primitively aquatic arthropod reveals conspicuous differences from the venoms of other predatory arthropods such as centipedes, scorpions, and spiders and contributes valuable information for ultimately disentangling the many factors shaping the biology and evolution of venoms and venomous species.

  4. Quantitative Proteomic Analysis of Venoms from Russian Vipers of Pelias Group: Phospholipases A2 are the Main Venom Components

    PubMed Central

    Kovalchuk, Sergey I.; Ziganshin, Rustam H.; Starkov, Vladislav G.; Tsetlin, Victor I.; Utkin, Yuri N.

    2016-01-01

    Venoms of most Russian viper species are poorly characterized. Here, by quantitative chromato-mass-spectrometry, we analyzed protein and peptide compositions of venoms from four Vipera species (V. kaznakovi, V. renardi, V. orlovi and V. nikolskii) inhabiting different regions of Russia. In all these species, the main components were phospholipases A2, their content ranging from 24% in V. orlovi to 65% in V. nikolskii. Altogether, enzyme content in venom of V. nikolskii reached ~85%. Among the non-enzymatic proteins, the most abundant were disintegrins (14%) in the V. renardi venom, C-type lectin like (12.5%) in V. kaznakovi, cysteine-rich venom proteins (12%) in V. orlovi and venom endothelial growth factors (8%) in V. nikolskii. In total, 210 proteins and 512 endogenous peptides were identified in the four viper venoms. They represented 14 snake venom protein families, most of which were found in the venoms of Vipera snakes previously. However, phospholipase B and nucleotide degrading enzymes were reported here for the first time. Compositions of V. kaznakovi and V. orlovi venoms were described for the first time and showed the greatest similarity among the four venoms studied, which probably reflected close relationship between these species within the “kaznakovi” complex. PMID:27077884

  5. Quantitative Proteomic Analysis of Venoms from Russian Vipers of Pelias Group: Phospholipases A₂ are the Main Venom Components.

    PubMed

    Kovalchuk, Sergey I; Ziganshin, Rustam H; Starkov, Vladislav G; Tsetlin, Victor I; Utkin, Yuri N

    2016-04-12

    Venoms of most Russian viper species are poorly characterized. Here, by quantitative chromato-mass-spectrometry, we analyzed protein and peptide compositions of venoms from four Vipera species (V. kaznakovi, V. renardi, V. orlovi and V. nikolskii) inhabiting different regions of Russia. In all these species, the main components were phospholipases A₂, their content ranging from 24% in V. orlovi to 65% in V. nikolskii. Altogether, enzyme content in venom of V. nikolskii reached ~85%. Among the non-enzymatic proteins, the most abundant were disintegrins (14%) in the V. renardi venom, C-type lectin like (12.5%) in V. kaznakovi, cysteine-rich venom proteins (12%) in V. orlovi and venom endothelial growth factors (8%) in V. nikolskii. In total, 210 proteins and 512 endogenous peptides were identified in the four viper venoms. They represented 14 snake venom protein families, most of which were found in the venoms of Vipera snakes previously. However, phospholipase B and nucleotide degrading enzymes were reported here for the first time. Compositions of V. kaznakovi and V. orlovi venoms were described for the first time and showed the greatest similarity among the four venoms studied, which probably reflected close relationship between these species within the "kaznakovi" complex.

  6. King cobra (Ophiophagus hannah) bites in Myanmar: venom antigen levels and development of venom antibodies.

    PubMed

    Tun-Pe; Aye-Aye-Myint; Warrell, D A; Tin-Myint

    1995-03-01

    Venom, venom IgG and IgM antibody and total serum IgG levels following king cobra bites in two reptile handlers were measured by enzyme immunoassay. The patient in case 1 received antivenom while the patient in case 2 did not. Case 1 made a complete recovery following the bite and produced a high titre short-lived antibody. Venom antigen was not detected in the sample taken 11 hr after antivenom. Case 2 had experienced two recent minor king cobra bites and had received traditional immunization 4 weeks before the accident reported here. He had developed only local swelling and suffered no neurological symptoms. Venom antigen measured at 1.45 hr after the bite was 132 ng/ml; this rapidly fell to 45 ng/ml over the next 30 min, and was no longer detectable 14 hr after the bite. The pattern of venom IgG and IgM antibody responses in both cases was comparable, except that in case 2 the venom IgG peak was maintained for 13 days, compared with 1 day in case 1; in case 2 it subsequently fell to low levels 8 weeks after the bite. Venom IgM appeared 1 day after the bite, peaked at day 7-9, rapidly tailed off on day 12-16 and was then undetectable from day 20 onwards in both. Total IgG level remained within normal limits in both. It is possible that previous bites and recent immunization contributed to the boosting of the venom IgG response in case 2.

  7. Dialyzed venom skin tests for identifying yellow jacket-allergic patients not detected using standard venom.

    PubMed

    Golden, David B K; Kelly, Denise; Hamilton, Robert G; Wang, Nae-Yuh; Kagey-Sobotka, Anne

    2009-01-01

    The chance of a nonspecific intradermal skin test response at venom concentrations greater than 1.0 microg/mL limits the diagnostic range and can interfere with the diagnosis of some affected patients. To compare the diagnostic ranges and clinical detection rates of skin tests using dialyzed yellow jacket venom (DYJV) and undialyzed YJV (UYJV), particularly in patients who have had negative venom skin test results. Both DYJV and UYJV from the same original lot were diluted from 100 microg/mL to skin test concentrations of 0.01, 0.1, 1.0, 3.0, and 10 microg/mL. Participants included 10 nonallergic controls, 20 patients with a positive history and positive skin test results using UYJV, and 24 patients with a positive history but negative skin test results using UYJV (17 of whom had a positive IgE anti-YJV serology). Dialyzed venom skin test results were positive at 10 microg/mL or less in 79% of patients with a positive history but negative skin test reactions using UYJV. The dialyzed venom skin test results showed a half-log shift to the left from the undialyzed venom results in linear regression analysis, indicating a greater detection rate with skin tests using DYJV. Results of skin tests with dialyzed venom were positive in 3 of 4 patients who had negative undialyzed venom skin test results and who experienced a systemic reaction to challenge stings. The DYJV improves the ability of skin tests to detect yellow jacket allergy and should be subject to further study.

  8. Venomous snakes of Costa Rica: biological and medical implications of their venom proteomic profiles analyzed through the strategy of snake venomics.

    PubMed

    Lomonte, Bruno; Fernández, Julián; Sanz, Libia; Angulo, Yamileth; Sasa, Mahmood; Gutiérrez, José María; Calvete, Juan J

    2014-06-13

    In spite of its small territory of ~50,000km(2), Costa Rica harbors a remarkably rich biodiversity. Its herpetofauna includes 138 species of snakes, of which sixteen pit vipers (family Viperidae, subfamily Crotalinae), five coral snakes (family Elapidae, subfamily Elapinae), and one sea snake (Family Elapidae, subfamily Hydrophiinae) pose potential hazards to human and animal health. In recent years, knowledge on the composition of snake venoms has expanded dramatically thanks to the development of increasingly fast and sensitive analytical techniques in mass spectrometry and separation science applied to protein characterization. Among several analytical strategies to determine the overall protein/peptide composition of snake venoms, the methodology known as 'snake venomics' has proven particularly well suited and informative, by providing not only a catalog of protein types/families present in a venom, but also a semi-quantitative estimation of their relative abundances. Through a collaborative research initiative between Instituto de Biomedicina de Valencia (IBV) and Instituto Clodomiro Picado (ICP), this strategy has been applied to the study of venoms of Costa Rican snakes, aiming to obtain a deeper knowledge on their composition, geographic and ontogenic variations, relationships to taxonomy, correlation with toxic activities, and discovery of novel components. The proteomic profiles of venoms from sixteen out of the 22 species within the Viperidae and Elapidae families found in Costa Rica have been reported so far, and an integrative view of these studies is hereby presented. In line with other venomic projects by research groups focusing on a wide variety of snakes around the world, these studies contribute to a deeper understanding of the biochemical basis for the diverse toxic profiles evolved by venomous snakes. In addition, these studies provide opportunities to identify novel molecules of potential pharmacological interest. Furthermore, the

  9. Fossilized venom: the unusually conserved venom profiles of Heloderma species (beaded lizards and gila monsters).

    PubMed

    Koludarov, Ivan; Jackson, Timothy N W; Sunagar, Kartik; Nouwens, Amanda; Hendrikx, Iwan; Fry, Bryan G

    2014-12-22

    Research into snake venoms has revealed extensive variation at all taxonomic levels. Lizard venoms, however, have received scant research attention in general, and no studies of intraclade variation in lizard venom composition have been attempted to date. Despite their iconic status and proven usefulness in drug design and discovery, highly venomous helodermatid lizards (gila monsters and beaded lizards) have remained neglected by toxinological research. Proteomic comparisons of venoms of three helodermatid lizards in this study has unravelled an unusual similarity in venom-composition, despite the long evolutionary time (~30 million years) separating H. suspectum from the other two species included in this study (H. exasperatum and H. horridum). Moreover, several genes encoding the major helodermatid toxins appeared to be extremely well-conserved under the influence of negative selection (but with these results regarded as preliminary due to the scarcity of available sequences). While the feeding ecologies of all species of helodermatid lizard are broadly similar, there are significant morphological differences between species, which impact upon relative niche occupation.

  10. Outcome survey of insect venom allergic patients with venom immunotherapy in a rural population.

    PubMed

    Roesch, Alexander; Boerzsoenyi, Julia; Babilas, Philipp; Landthaler, Michael; Szeimies, Rolf-Markus

    2008-04-01

    Hymenoptera venom anaphylaxis is a frightening event that affects physical and psychical functioning. Retrospective survey of 182 Hymenoptera venom allergic patients living in a rural area using a questionnaire targeting on patients' satisfaction during therapy, fear of anaphylactic recurrences and changes in lifestyle before and after venom immunotherapy (VIT). Additionally, patients' self-assessment of quality of life, daily outdoor time and re-sting rate were recorded. 146 patients returned the questionnaire (58.9% male, 41.1% female, 25.3% honey bee allergic, 67.8% wasp allergic, 41.1% re-sting rate, mean follow-up time 6.5 years). Measurement of the parameters fear, satisfaction and changes in lifestyle revealed a significant improvement after VIT. This correlated with the patients'self-assessment of quality of life,when 89.7% declared an improvement after VIT. Although the improvement was higher in patients with re-stings, also patients without re-stings clearly benefited from VIT. Interestingly, females were significantly more affected by Hymenoptera venom allergy than males,whereas both genders showed a similar improvement after VIT. Patients with Hymenoptera venom sting allergy significantly benefit from VIT in regard to both biological and psychological outcome. VIT should still be provided to all Hymenoptera venom allergic patients as standard of care.

  11. Fossilized Venom: The Unusually Conserved Venom Profiles of Heloderma Species (Beaded Lizards and Gila Monsters)

    PubMed Central

    Koludarov, Ivan; Jackson, Timothy N. W.; Sunagar, Kartik; Nouwens, Amanda; Hendrikx, Iwan; Fry, Bryan G.

    2014-01-01

    Research into snake venoms has revealed extensive variation at all taxonomic levels. Lizard venoms, however, have received scant research attention in general, and no studies of intraclade variation in lizard venom composition have been attempted to date. Despite their iconic status and proven usefulness in drug design and discovery, highly venomous helodermatid lizards (gila monsters and beaded lizards) have remained neglected by toxinological research. Proteomic comparisons of venoms of three helodermatid lizards in this study has unravelled an unusual similarity in venom-composition, despite the long evolutionary time (~30 million years) separating H. suspectum from the other two species included in this study (H. exasperatum and H. horridum). Moreover, several genes encoding the major helodermatid toxins appeared to be extremely well-conserved under the influence of negative selection (but with these results regarded as preliminary due to the scarcity of available sequences). While the feeding ecologies of all species of helodermatid lizard are broadly similar, there are significant morphological differences between species, which impact upon relative niche occupation. PMID:25533521

  12. Centipede venom: recent discoveries and current state of knowledge.

    PubMed

    Undheim, Eivind A B; Fry, Bryan G; King, Glenn F

    2015-02-25

    Centipedes are among the oldest extant venomous predators on the planet. Armed with a pair of modified, venom-bearing limbs, they are an important group of predatory arthropods and are infamous for their ability to deliver painful stings. Despite this, very little is known about centipede venom and its composition. Advances in analytical tools, however, have recently provided the first detailed insights into the composition and evolution of centipede venoms. This has revealed that centipede venom proteins are highly diverse, with 61 phylogenetically distinct venom protein and peptide families. A number of these have been convergently recruited into the venoms of other animals, providing valuable information on potential underlying causes of the occasionally serious complications arising from human centipede envenomations. However, the majority of venom protein and peptide families bear no resemblance to any characterised protein or peptide family, highlighting the novelty of centipede venoms. This review highlights recent discoveries and summarises the current state of knowledge on the fascinating venom system of centipedes.

  13. Centipede Venom: Recent Discoveries and Current State of Knowledge

    PubMed Central

    Undheim, Eivind A. B.; Fry, Bryan G.; King, Glenn F.

    2015-01-01

    Centipedes are among the oldest extant venomous predators on the planet. Armed with a pair of modified, venom-bearing limbs, they are an important group of predatory arthropods and are infamous for their ability to deliver painful stings. Despite this, very little is known about centipede venom and its composition. Advances in analytical tools, however, have recently provided the first detailed insights into the composition and evolution of centipede venoms. This has revealed that centipede venom proteins are highly diverse, with 61 phylogenetically distinct venom protein and peptide families. A number of these have been convergently recruited into the venoms of other animals, providing valuable information on potential underlying causes of the occasionally serious complications arising from human centipede envenomations. However, the majority of venom protein and peptide families bear no resemblance to any characterised protein or peptide family, highlighting the novelty of centipede venoms. This review highlights recent discoveries and summarises the current state of knowledge on the fascinating venom system of centipedes. PMID:25723324

  14. Categorization of venoms according to bonding properties: An immunological overview.

    PubMed

    Ibrahim, Nihal M; El-Kady, Ebtsam M; Asker, Mohsen S

    2016-02-01

    In this report, we present a study on the antigenic cross-reactivity of various venoms from the most dangerous Egyptian snakes and scorpions belonging to families Elapidae, Viperidae and Buthidae. The study was carried out with special reference to bonding properties between venoms and antivenoms and their involvement in the formation of specific and/or cross-reactive interactions. The homologous polyclonal antivenoms showed high reactivity to the respective venoms and cross-reacted with varying degrees to other non-homologous venoms. Assorting the antivenoms according to their susceptibility to dissociation by different concentrations of NH4SCN revealed that most of the antibodies involved in homologous venom-antivenom interactions were highly avid; building up strong venom-antivenom bonding. Whereas cross-reactions due to heterologous interactions were mediated by less avid antibodies that ultimately led to the formation of venom-antivenom bonding of different power strengths depending on the antigenic similarity and hence on the phylogenetic relationship of the tested venom. A new parameter evaluating high and low avid interactions, designated as H/L value, for each antigen-antibody bonding was initiated and used as an indicator of bonding strength between different venom-antivenom partners. H/L values were many folds higher than 1 for homologous and closely related venoms, 1 or around 1 for cross-reactive venoms, whereas venoms from unrelated remote sources recorded H/L values far less than 1. Using well defined polyclonal antivenoms, H/L value was successfully used to assign eight unknown venoms to their animal families and the results were confirmed by species-specific ELISA and immunoblotting assays. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Simplification of intradermal skin testing in Hymenoptera venom allergic children.

    PubMed

    Cichocka-Jarosz, Ewa; Stobiecki, Marcin; Brzyski, Piotr; Rogatko, Iwona; Nittner-Marszalska, Marita; Sztefko, Krystyna; Czarnobilska, Ewa; Lis, Grzegorz; Nowak-Węgrzyn, Anna

    2017-03-01

    The direct comparison between children and adults with Hymenoptera venom anaphylaxis (HVA) has never been extensively reported. Severe HVA with IgE-documented mechanism is the recommendation for venom immunotherapy, regardless of age. To determine the differences in the basic diagnostic profile between children and adults with severe HVA and its practical implications. We reviewed the medical records of 91 children and 121 adults. Bee venom allergy was exposure dependent, regardless of age (P < .001). Atopy was more common in children (P = .01), whereas cardiovascular comorbidities were present almost exclusively in adults (P = .001). In the bee venom allergic group, specific IgE levels were significantly higher in children (29.5 kUA/L; interquartile range, 11.30-66.30 kUA/L) compared with adults (5.10 kUA/L; interquartile range, 2.03-8.30 kUA/L) (P < .001). Specific IgE levels for culprit insect venom were higher in bee venom allergic children compared with the wasp venom allergic children (P < .001). In adults, intradermal tests revealed higher sensitivity, accompanied by larger area of skin reactions, regardless of type of venom. At concentrations lower than 0.1 μg/mL, 16% of wasp venom allergic children and 39% of bee venom allergic children had positive intradermal test results. The median tryptase level was significantly higher in adults than in children for the entire study group (P = .002), as well as in bee (P = .002) and wasp venom allergic groups (P = .049). The basic diagnostic profile in severe HVA reactors is age dependent. Lower skin test reactivity to culprit venom in children may have practical application in starting the intradermal test procedure with higher venom concentrations. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Modulation of intracellular Ca2+ levels by Scorpaenidae venoms.

    PubMed

    Church, Jarrod E; Moldrich, Randal X; Beart, Philip M; Hodgson, Wayne C

    2003-05-01

    The crude venoms of the soldierfish (Gymnapistes marmoratus), the lionfish (Pterois volitans) and the stonefish (Synanceia trachynis) display pronounced neuromuscular activity. Since [Ca(2+)](i) is a key regulator in many aspects of neuromuscular function we sought to determine its involvement in the neuromuscular actions of the venoms. In the chick biventer cervicis muscle, all three venoms produced a sustained contraction (approx 20-30% of 1mM acetylcholine). Blockade of nicotinic receptors with tubocurarine (10 micro M) failed to attenuate the contractile response to either G. marmoratus venom or P. volitans venom, but produced slight inhibition of the response to S. trachynis venom. All three venoms produced a rise in intracellular Ca(2+) (approx. 200-300% of basal) in cultured murine cortical neurons. The Ca(2+)-channel blockers omega-conotoxin MVIIC, omega-conotoxin GVIA, omega-agatoxin IVa and nifedipine (each at 1 micro M) potentiated the increase in [Ca(2+)](i) in response to G. marmoratus venom and P. volitans venom, while attenuating the response to S. trachynis venom. Removal of extracellular Ca(2+), replacement of Ca(2+) with La(3+) (0.5mM), or addition of stonefish antivenom (3units/ml) inhibited both the venom-induced increase in [Ca(2+)](i) in cultured neurones and contraction in chick biventer cervicis muscle. Venom-induced increases in [Ca(2+)](i) correlated with an increased cell death of cultured neurones as measured using propidium iodide (1 micro g/ml). Morphological analysis revealed cellular swelling and neurite loss consistent with necrosis. These data indicate that the effects of all three venoms are due in part to an increase in intracellular Ca(2+), possibly via the formation of pores in the cellular membrane which, under certain conditions, can lead to necrosis.

  17. Early evolution of the venom system in lizards and snakes.

    PubMed

    Fry, Bryan G; Vidal, Nicolas; Norman, Janette A; Vonk, Freek J; Scheib, Holger; Ramjan, S F Ryan; Kuruppu, Sanjaya; Fung, Kim; Hedges, S Blair; Richardson, Michael K; Hodgson, Wayne C; Ignjatovic, Vera; Summerhayes, Robyn; Kochva, Elazar

    2006-02-02

    Among extant reptiles only two lineages are known to have evolved venom delivery systems, the advanced snakes and helodermatid lizards (Gila Monster and Beaded Lizard). Evolution of the venom system is thought to underlie the impressive radiation of the advanced snakes (2,500 of 3,000 snake species). In contrast, the lizard venom system is thought to be restricted to just two species and to have evolved independently from the snake venom system. Here we report the presence of venom toxins in two additional lizard lineages (Monitor Lizards and Iguania) and show that all lineages possessing toxin-secreting oral glands form a clade, demonstrating a single early origin of the venom system in lizards and snakes. Construction of gland complementary-DNA libraries and phylogenetic analysis of transcripts revealed that nine toxin types are shared between lizards and snakes. Toxinological analyses of venom components from the Lace Monitor Varanus varius showed potent effects on blood pressure and clotting ability, bioactivities associated with a rapid loss of consciousness and extensive bleeding in prey. The iguanian lizard Pogona barbata retains characteristics of the ancestral venom system, namely serial, lobular non-compound venom-secreting glands on both the upper and lower jaws, whereas the advanced snakes and anguimorph lizards (including Monitor Lizards, Gila Monster and Beaded Lizard) have more derived venom systems characterized by the loss of the mandibular (lower) or maxillary (upper) glands. Demonstration that the snakes, iguanians and anguimorphs form a single clade provides overwhelming support for a single, early origin of the venom system in lizards and snakes. These results provide new insights into the evolution of the venom system in squamate reptiles and open new avenues for biomedical research and drug design using hitherto unexplored venom proteins.

  18. Peptide toxins from Conus geographus venom.

    PubMed

    Gray, W R; Luque, A; Olivera, B M; Barrett, J; Cruz, L J

    1981-05-25

    Three homologous toxic peptides which cause postsynaptic inhibition at the vertebrate neuromuscular junction have been purified from the venom of the marine snail Conus geographus. Their amino acid sequences are: (formula see text) The biologically active peptides are monomeric, with internal disulfide bonds.

  19. Proteomics and deep sequencing comparison of seasonally active venom glands in the platypus reveals novel venom peptides and distinct expression profiles.

    PubMed

    Wong, Emily S W; Morgenstern, David; Mofiz, Ehtesham; Gombert, Sara; Morris, Katrina M; Temple-Smith, Peter; Renfree, Marilyn B; Whittington, Camilla M; King, Glenn F; Warren, Wesley C; Papenfuss, Anthony T; Belov, Katherine

    2012-11-01

    The platypus is a venomous monotreme. Male platypuses possess a spur on their hind legs that is connected to glands in the pelvic region. They produce venom only during the breeding season, presumably to fight off conspecifics. We have taken advantage of this unique seasonal production of venom to compare the transcriptomes of in- and out-of-season venom glands, in conjunction with proteomic analysis, to identify previously undiscovered venom genes. Comparison of the venom glands revealed distinct gene expression profiles that are consistent with changes in venom gland morphology and venom volumes in and out of the breeding season. Venom proteins were identified through shot-gun sequenced venom proteomes of three animals using RNA-seq-derived transcripts for peptide-spectral matching. 5,157 genes were expressed in the venom glands, 1,821 genes were up-regulated in the in-season gland, and 10 proteins were identified in the venom. New classes of platypus-venom proteins identified included antimicrobials, amide oxidase, serpin protease inhibitor, proteins associated with the mammalian stress response pathway, cytokines, and other immune molecules. Five putative toxins have only been identified in platypus venom: growth differentiation factor 15, nucleobindin-2, CD55, a CXC-chemokine, and corticotropin-releasing factor-binding protein. These novel venom proteins have potential biomedical and therapeutic applications and provide insights into venom evolution.

  20. Proteomics and Deep Sequencing Comparison of Seasonally Active Venom Glands in the Platypus Reveals Novel Venom Peptides and Distinct Expression Profiles*

    PubMed Central

    Wong, Emily S. W.; Morgenstern, David; Mofiz, Ehtesham; Gombert, Sara; Morris, Katrina M.; Temple-Smith, Peter; Renfree, Marilyn B.; Whittington, Camilla M.; King, Glenn F.; Warren, Wesley C.; Papenfuss, Anthony T.; Belov, Katherine

    2012-01-01

    The platypus is a venomous monotreme. Male platypuses possess a spur on their hind legs that is connected to glands in the pelvic region. They produce venom only during the breeding season, presumably to fight off conspecifics. We have taken advantage of this unique seasonal production of venom to compare the transcriptomes of in- and out-of-season venom glands, in conjunction with proteomic analysis, to identify previously undiscovered venom genes. Comparison of the venom glands revealed distinct gene expression profiles that are consistent with changes in venom gland morphology and venom volumes in and out of the breeding season. Venom proteins were identified through shot-gun sequenced venom proteomes of three animals using RNA-seq-derived transcripts for peptide-spectral matching. 5,157 genes were expressed in the venom glands, 1,821 genes were up-regulated in the in-season gland, and 10 proteins were identified in the venom. New classes of platypus-venom proteins identified included antimicrobials, amide oxidase, serpin protease inhibitor, proteins associated with the mammalian stress response pathway, cytokines, and other immune molecules. Five putative toxins have only been identified in platypus venom: growth differentiation factor 15, nucleobindin-2, CD55, a CXC-chemokine, and corticotropin-releasing factor-binding protein. These novel venom proteins have potential biomedical and therapeutic applications and provide insights into venom evolution. PMID:22899769

  1. Snake venomics across genus Lachesis. Ontogenetic changes in the venom composition of Lachesis stenophrys and comparative proteomics of the venoms of adult Lachesis melanocephala and Lachesis acrochorda.

    PubMed

    Madrigal, Marvin; Sanz, Libia; Flores-Díaz, Marietta; Sasa, Mahmood; Núñez, Vitelbina; Alape-Girón, Alberto; Calvete, Juan J

    2012-12-21

    We report the proteomic analysis of ontogenetic changes in venom composition of the Central American bushmaster, Lachesis stenophrys, and the characterization of the venom proteomes of two congeneric pitvipers, Lachesis melanocephala (black-headed bushmaster) and Lachesis acrochorda (Chochoan bushmaster). Along with the previous characterization of the venom proteome of Lachesis muta muta (from Bolivia), our present outcome enables a comparative overview of the composition and distribution of the toxic proteins across genus Lachesis. Comparative venomics revealed the close kinship of Central American L. stenophrys and L. melanocephala and support the elevation of L. acrochorda to species status. Major ontogenetic changes in the toxin composition of L. stenophrys venom involves quantitative changes in the concentration of vasoactive peptides and serine proteinases, which steadily decrease from birth to adulthood, and age-dependent de novo biosynthesis of Gal-lectin and snake venom metalloproteinases (SVMPs). The net result is a shift from a bradykinin-potentiating and C-type natriuretic peptide (BPP/C-NP)-rich and serine proteinase-rich venom in newborns and 2-years-old juveniles to a (PI>PIII) SVMP-rich venom in adults. Notwithstanding minor qualitative and quantitative differences, the venom arsenals of L. melanocephala and L. acrochorda are broadly similar between themselves and also closely mirror those of adult L. stenophrys and L. muta venoms. The high conservation of the overall composition of Central and South American bushmaster venoms provides the ground for rationalizing the "Lachesis syndrome", characterized by vagal syntomatology, sensorial disorders, hematologic, and cardiovascular manifestations, documented in envenomings by different species of this wide-ranging genus. This finding let us predict that monospecific Lachesic antivenoms may exhibit paraspecificity against all congeneric species. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. One Fish Two Fish.

    ERIC Educational Resources Information Center

    Hoffman, Michele

    1998-01-01

    This activity explains fisheries resource management to seven-year olds. First-grade students learn concepts such as offspring viability, life expectancy, and distribution of species, which help to determine when, where, and how people fish and the importance of fishing responsibly. Lists materials, procedures, and extensions. (SJR)

  3. One Fish Two Fish.

    ERIC Educational Resources Information Center

    Hoffman, Michele

    1998-01-01

    This activity explains fisheries resource management to seven-year olds. First-grade students learn concepts such as offspring viability, life expectancy, and distribution of species, which help to determine when, where, and how people fish and the importance of fishing responsibly. Lists materials, procedures, and extensions. (SJR)

  4. Bee venom hypersensitivity and its management: patients perception of venom desensitisation.

    PubMed

    Lui, C L; Heddle, R J; Kupa, A; Coates, T; Roberts-Thomson, P J

    1995-12-01

    The objectives of the study were to review bee venom immunotherapy from the patient's perspective: in particular its benefits and its problems, and to investigate any genetic tendency for bee venom hypersensitivity. A self administered, 9 item questionnaire was sent to 219 patients who had undergone either inpatient or outpatient bee venom immunotherapy at Flinders Medical Center. The clinic records of these patients were also reviewed. The controls for the genetic study were sought from patients, staff and students at Flinders University and Flinders Medical Centre. One hundred and forty-six questionnaires (some incomplete and anonymous) were received. The female to male ratio was 1:2.5. The age at the time of the initial anaphylactic reaction to a bee sting ranged between 2 to 59 years, with 67% of patients being less then 20 years old. Forty percent of patients underwent venom immunotherapy for a period less than 2 years with only 11% maintaining therapy for the recommended period of 5 years or more. Thirty three percent of patients stopped their therapy on their own accord. Bee stings occurring during bee venom immunotherapy (n = 56) were generally well tolerated except in 8 subjects, 7 of whom had not reached the maintenance dose. The reduction in systemic reactions to subsequent bee stings was significantly better in the study group receiving bee venom than in an historic control group treated with whole bee extract (p = 0.03). Fear of bee stings and restricted life styles were improved during or after venom immunotherapy. The frequency of a positive family history of systemic reactions to bee stings in the patient cohort was 31%, whereas in controls it was 15% (p = 0.013). Bee venom immunotherapy has dual benefits: patients are protected from subsequent sting anaphylaxis and there is reduced psychological morbidity. However, to be effective, venom immunotherapy requires a prolonged period of carefully supervised treatment and each venom injection can cause

  5. Snake venoms are integrated systems, but abundant venom proteins evolve more rapidly.

    PubMed

    Aird, Steven D; Aggarwal, Shikha; Villar-Briones, Alejandro; Tin, Mandy Man-Ying; Terada, Kouki; Mikheyev, Alexander S

    2015-08-28

    While many studies have shown that extracellular proteins evolve rapidly, how selection acts on them remains poorly understood. We used snake venoms to understand the interaction between ecology, expression level, and evolutionary rate in secreted protein systems. Venomous snakes employ well-integrated systems of proteins and organic constituents to immobilize prey. Venoms are generally optimized to subdue preferred prey more effectively than non-prey, and many venom protein families manifest positive selection and rapid gene family diversification. Although previous studies have illuminated how individual venom protein families evolve, how selection acts on venoms as integrated systems, is unknown. Using next-generation transcriptome sequencing and mass spectrometry, we examined microevolution in two pitvipers, allopatrically separated for at least 1.6 million years, and their hybrids. Transcriptomes of parental species had generally similar compositions in regard to protein families, but for a given protein family, the homologs present and concentrations thereof sometimes differed dramatically. For instance, a phospholipase A2 transcript comprising 73.4 % of the Protobothrops elegans transcriptome, was barely present in the P. flavoviridis transcriptome (<0.05 %). Hybrids produced most proteins found in both parental venoms. Protein evolutionary rates were positively correlated with transcriptomic and proteomic abundances, and the most abundant proteins showed positive selection. This pattern holds with the addition of four other published crotaline transcriptomes, from two more genera, and also for the recently published king cobra genome, suggesting that rapid evolution of abundant proteins may be generally true for snake venoms. Looking more broadly at Protobothrops, we show that rapid evolution of the most abundant components is due to positive selection, suggesting an interplay between abundance and adaptation. Given log-scale differences in toxin

  6. Transcriptome analysis of the venom gland of the scorpion Scorpiops jendeki: implication for the evolution of the scorpion venom arsenal

    PubMed Central

    Ma, Yibao; Zhao, Ruiming; He, Yawen; Li, Songryong; Liu, Jun; Wu, Yingliang; Cao, Zhijian; Li, Wenxin

    2009-01-01

    Background The family Euscorpiidae, which covers Europe, Asia, Africa, and America, is one of the most widely distributed scorpion groups. However, no studies have been conducted on the venom of a Euscorpiidae species yet. In this work, we performed a transcriptomic approach for characterizing the venom components from a Euscorpiidae scorpion, Scorpiops jendeki. Results There are ten known types of venom peptides and proteins obtained from Scorpiops jendeki. Great diversity is observed in primary sequences of most highly expressed types. The most highly expressed types are cytolytic peptides and serine proteases. Neurotoxins specific for sodium channels, which are major groups of venom components from Buthidae scorpions, are not detected in this study. In addition to those known types of venom peptides and proteins, we also obtain nine atypical types of venom molecules which haven't been observed in any other scorpion species studied to date. Conclusion This work provides the first set of cDNAs from Scorpiops jendeki, and one of the few transcriptomic analyses from a scorpion. This allows the characterization of a large number of venom molecules, belonging to either known or atypical types of scorpion venom peptides and proteins. Besides, our work could provide some clues to the evolution of the scorpion venom arsenal by comparison with venom data from other scorpion lineages. PMID:19570192

  7. Proteome and phosphoproteome analysis of honeybee (Apis mellifera) venom collected from electrical stimulation and manual extraction of the venom gland

    PubMed Central

    2013-01-01

    Background Honeybee venom is a complicated defensive toxin that has a wide range of pharmacologically active compounds. Some of these compounds are useful for human therapeutics. There are two major forms of honeybee venom used in pharmacological applications: manually (or reservoir disrupting) extracted glandular venom (GV), and venom extracted through the use of electrical stimulation (ESV). A proteome comparison of these two venom forms and an understanding of the phosphorylation status of ESV, are still very limited. Here, the proteomes of GV and ESV were compared using both gel-based and gel-free proteomics approaches and the phosphoproteome of ESV was determined through the use of TiO2 enrichment. Results Of the 43 proteins identified in GV, < 40% were venom toxins, and > 60% of the proteins were non-toxic proteins resulting from contamination by gland tissue damage during extraction and bee death. Of the 17 proteins identified in ESV, 14 proteins (>80%) were venom toxic proteins and most of them were found in higher abundance than in GV. Moreover, two novel proteins (dehydrogenase/reductase SDR family member 11-like and histone H2B.3-like) and three novel phosphorylation sites (icarapin (S43), phospholipase A-2 (T145), and apamin (T23)) were identified. Conclusions Our data demonstrate that venom extracted manually is different from venom extracted using ESV, and these differences may be important in their use as pharmacological agents. ESV may be more efficient than GV as a potential pharmacological source because of its higher venom protein content, production efficiency, and without the need to kill honeybee. The three newly identified phosphorylated venom proteins in ESV may elicit a different immune response through the specific recognition of antigenic determinants. The two novel venom proteins extend our proteome coverage of honeybee venom. PMID:24199871

  8. Antitumor effect of Bothrops jararaca venom.

    PubMed Central

    da Silva, Reinaldo J; da Silva, Márcia G; Vilela, Lízia C; Fecchio, Denise

    2002-01-01

    Many experimental studies have been carried out using snake venoms for the treatment of animal tumors, with controversial results. While some authors have reported an antitumor effect of treatment with specific snake venom fractions, others have reported no effects after this treatment. The aim of this study was to evaluate the effect of Bothrops jararaca venom (BjV) on Ehrlich ascites tumor (EAT) cells in vivo and in vitro. In the in vivo study, Swiss mice were inoculated with EAT cells by the intraperitoneal (i.p.) route and treated with BjV venom (0.4 mg/kg, i.p.), on the 1st, 4th, 7th, 10th, and 13th days. Mice were evaluated for total and differential cells number on the 2nd, 5th, 8th, 11th and 14th days. The survival time was also evaluated after 60 days of tumor growth. In the in vitro study, EAT and normal peritoneal cells were cultivated in the presence of different BjV concentrations (2.5, 5.0, 10.0, 20.0, 40.0, and 80 microg) and viability was verified after 3, 6, 12 and 24 h of cultivation. Results were analyzed statistically by the Kruskal-Wallis and Tukey tests at the 5% level of significance. It was observed that in vivo treatment with BjV induced tumor growth inhibition, increased animal survival time, decreased mortality, increased the influx of polymorphonuclear leukocytes on the early stages of tumor growth, and did not affect the mononuclear cells number. In vitro treatment with BjV produced a dose-dependent toxic effect on EAT and peritoneal cells, with higher effects against peritoneal cells. Taken together, our results demonstrate that BjV has an important antitumor effect. This is the first report showing this in vivo effect for this venom. PMID:12061431

  9. The strategy used by some piscivorous cone snails to capture their prey: the effects of their venoms on vertebrates and on isolated neuromuscular preparations.

    PubMed

    Le Gall, F; Favreau, P; Richard, G; Letourneux, Y; Molgó, J

    1999-07-01

    Three piscivorous Conus species, C. ermineus, C. consor and C. catus were acclimatized in aquaria. The study of their strategy to capture the prey and details of their radula's morphology revealed that all of them used a 'hook and line' strategy which consists of immobilizing the prey rapidly before engulfing it. The venoms from these piscivorous species clearly elicit, when injected into fish, an excitotoxic shock characterized by a sudden tetanus of the prey. In mammals, the venoms induce both flaccid paralysis via i.p. injection and seizures via i.c.v. injection. Intracellular recordings from frog nerve-muscle preparations revealed that the venoms from these Conus species first caused spontaneous synaptic potentials which in turn triggered muscle action potentials. Such spontaneous activity is due to an increased nerve terminal excitability. In addition, the venoms suppressed neuromuscular transmission probably by blocking postsynaptic nicotinic acetylcholine receptors. No direct effect of these Conus venoms was observed on the membrane of skeletal muscle fibres. In conclusion, C. ermineus, C. consor and C. catus, which have not securely tethered their prey used a mixture of toxins which target both pre-and postsynaptic elements of the neuromuscular junction and which produce rapid immobilization of their prey.

  10. Histological characterization of the special venom secretory cells in the stinger of rays in the northern waters of Persian Gulf and Oman Sea.

    PubMed

    Dehghani, Hadi; Sajjadi, Mir Masoud; Parto, Paria; Rajaian, Hamid; Mokhlesi, Amin

    2010-06-01

    Rays are common elasmobranches in the northern waters of Persian Gulf and Oman Sea that may have one or more mineralized serrated stingers on the whip-like tail. The stingers are covered by epidermal cells among which some can produce venom. When these animals are dorsally touched, the stinger can be introduced into the aggressor by a whip reflex mechanism of the tail when the pectoral fins are touched, causing severe mechanical injuries and inoculating the venom. The exact localization of the venom secretory cells in the stinger of different species is controversial, but it is known that the cells are preferentially located in the ventro-lateral grooves in marine stingrays. A comparative morphological characterization of the stinger epidermal tissue of different ray species in the northern part of Persian Gulf and Oman Sea was carried out in this study. EDTA was used for decalcification of stings and conventional histological processes were subsequently employed. The results indicated that structure of dermis and epidermis layers of stings in all species are similar to the structure of corresponding layers in other parts of fish's body. The results of the present study have shown that all examined species of Dasyatidae family, but not Myliobatidae and Gymnuridae families, had venom secretory cells. Distribution of venom secretory cells varies in each species and is often located around or inside the stinger ventro-lateral grooves. These differences among the stingers of various species may explain the envenomation severity in these species. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Human antibody fragments specific for Bothrops jararacussu venom reduce the toxicity of other Bothrops sp. venoms.

    PubMed

    Roncolato, Eduardo Crosara; Pucca, Manuela Berto; Funayama, Jaqueline Carlos; Bertolini, Thaís Barboza; Campos, Lucas Benício; Barbosa, José Elpidio

    2013-01-01

    Approximately 20,000 snakebites are registered each year in Brazil. The classical treatment for venomous snakebite involves the administration of sera obtained from immunized horses. Moreover, the production and care of horses is costly, and the use of heterologous sera can cause hypersensitivity reactions. The production of human antibody fragments by phage display technology is seen as a means of overcoming some of these disadvantages. The studies here attempted to test human monoclonal antibodies specific to Bothrops jararacussu against other Bothrops sp. venoms, using the Griffin.1 library of human single-chain fragment-variable (scFv) phage antibodies. Using the Griffin.1 phage antibody library, this laboratory previously produced scFvs capable of inhibiting the phospholipase and myotoxic activities of Bothrops jararacussu venom. The structural and functional similarities of the various forms of phospholipase A2 (PLA₂) in Bothrops venom served as the basis for the present study wherein the effectiveness of those same scFvs were evaluated against B. jararaca, B. neuwiedi, and B. moojeni venoms. Each clone was found to recognize all three Bothrops venoms, and purified scFvs partially inhibited their in vitro phospholipase activity. In vivo assays demonstrated that the scFv clone P2B7 reduced myotoxicity and increased the survival of animals that received the test venoms. The results here indicate that the scFv P2B7 is a candidate for inclusion in a mixture of specific antibodies to produce a human anti-bothropic sera. This data demonstrates that the human scFv P2B7 represents an alternative therapeutic approach to heterologous anti-bothropic sera available today.

  12. Antibacterial properties of KwaZulu natal snake venoms.

    PubMed

    Blaylock, R S

    2000-11-01

    The objective was to ascertain whether local snake venoms have antibacterial properties. The venoms of the common night adder (Causus rhombeatus), gaboon adder (Bitis gabonica), puff adder (Bitis arietans), black mamba (Dendroaspis polylepis), eastern green mamba (Dendroaspis augusticeps), forest cobra (Naja melanoleuca), snouted cobra (Naja annulifera) and Mozambique spitting cobra (Naja mossambica) were collected and, by gel diffusion, tested against the bacteria Staphylococcus aureus, Escherichia coli, Pseudomonas aeriginosa, Bacteriodes fragilis, Bacteroides intermedius, Clostridium sordellii and Clostridium perfringens. All snake venoms showed antibacterial activity, with the adders showing most activity against the aerobes while the cobras showed lesser, but equal activity against the aerobes and anaerobes. Black mamba venom only showed activity against C. perfringens. In conclusion, local snake venoms have antibacterial properties which are dependent on the venom and bacterial type; and in the Naja spp., for anaerobic bacteria, diminish in winter. There is liable to be more than one toxin component responsible.

  13. Animal venom studies: Current benefits and future developments.

    PubMed

    Utkin, Yuri N

    2015-05-26

    Poisonous organisms are represented in many taxa, including kingdom Animalia. During evolution, animals have developed special organs for production and injection of venoms. Animal venoms are complex mixtures, compositions of which depend on species producing venom. The most known and studied poisonous terrestrial animals are snakes, scorpions and spiders. Among marine animals, these are jellyfishes, anemones and cone snails. The toxic substances in the venom of these animals are mainly of protein and peptide origin. Recent studies have indicated that the single venom may contain up to several hundred different components producing diverse physiological effects. Bites or stings by certain poisonous species result in severe envenomations leading in some cases to death. This raises the problem of bite treatment. The most effective treatment so far is the application of antivenoms. To enhance the effectiveness of such treatments, the knowledge of venom composition is needed. On the other hand, venoms contain substances with unique biological properties, which can be used both in basic science and in clinical applications. The best example of toxin application in basic science is α-bungarotoxin the discovery of which made a big impact on the studies of nicotinic acetylcholine receptor. Today compositions of venom from many species have already been examined. Based on these data, one can conclude that venoms contain a large number of individual components belonging to a limited number of structural types. Often minor changes in the amino acid sequence give rise to new biological properties. Change in the living conditions of poisonous animals lead to alterations in the composition of venoms resulting in appearance of new toxins. At the same time introduction of new methods of proteomics and genomics lead to discoveries of new compounds, which may serve as research tools or as templates for the development of novel drugs. The application of these sensitive and

  14. Modern trends in animal venom research - omics and nanomaterials.

    PubMed

    Utkin, Yuri N

    2017-02-26

    Animal venom research is a specialized investigation field, in which a number of different methods are used and this array is constantly expanding. Thus, recently emerged omics and nanotechnologies have already been successfully applied to venom research. Animal venoms have been studied for quite a long time. The traditional reductionist approach has been to isolate individual toxins and then study their structure and function. Unfortunately, the characterization of the venom as a whole system and its multiple effects on an entire organism were not possible until recent times. The development of new methods in mass spectrometry and sequencing have allowed such characterizations of venom, encompassing the identification of new toxins present in venoms at extremely low concentrations to changes in metabolism of prey organisms after envenomation. In particular, this type of comprehensive research has become possible due to the development of the various omics technologies: Proteomics, peptidomics, transcriptomics, genomics and metabolomics. As in other research fields, these omics technologies ushered in a revolution for venom studies, which is now entering the era of big data. Nanotechnology is a very new branch of technology and developing at an extremely rapid pace. It has found application in many spheres and has not bypassed the venom studies. Nanomaterials are quite promising in medicine, and most studies combining venoms and nanomaterials are dedicated to medical applications. Conjugates of nanoparticles with venom components have been proposed for use as drugs or diagnostics. For example, nanoparticles conjugated with chlorotoxin - a toxin in scorpion venom, which has been shown to bind specifically to glioma cells - are considered as potential glioma-targeted drugs, and conjugates of neurotoxins with fluorescent semiconductor nanoparticles or quantum dots may be used to detect endogenous targets expressed in live cells. The data on application of omics and

  15. Animal venom studies: Current benefits and future developments

    PubMed Central

    Utkin, Yuri N

    2015-01-01

    Poisonous organisms are represented in many taxa, including kingdom Animalia. During evolution, animals have developed special organs for production and injection of venoms. Animal venoms are complex mixtures, compositions of which depend on species producing venom. The most known and studied poisonous terrestrial animals are snakes, scorpions and spiders. Among marine animals, these are jellyfishes, anemones and cone snails. The toxic substances in the venom of these animals are mainly of protein and peptide origin. Recent studies have indicated that the single venom may contain up to several hundred different components producing diverse physiological effects. Bites or stings by certain poisonous species result in severe envenomations leading in some cases to death. This raises the problem of bite treatment. The most effective treatment so far is the application of antivenoms. To enhance the effectiveness of such treatments, the knowledge of venom composition is needed. On the other hand, venoms contain substances with unique biological properties, which can be used both in basic science and in clinical applications. The best example of toxin application in basic science is α-bungarotoxin the discovery of which made a big impact on the studies of nicotinic acetylcholine receptor. Today compositions of venom from many species have already been examined. Based on these data, one can conclude that venoms contain a large number of individual components belonging to a limited number of structural types. Often minor changes in the amino acid sequence give rise to new biological properties. Change in the living conditions of poisonous animals lead to alterations in the composition of venoms resulting in appearance of new toxins. At the same time introduction of new methods of proteomics and genomics lead to discoveries of new compounds, which may serve as research tools or as templates for the development of novel drugs. The application of these sensitive and

  16. Widespread Chemical Detoxification of Alkaloid Venom by Formicine Ants.

    PubMed

    LeBrun, Edward G; Diebold, Peter J; Orr, Matthew R; Gilbert, Lawrence E

    2015-10-01

    The ability to detoxify defensive compounds of competitors provides key ecological advantages that can influence community-level processes. Although common in plants and bacteria, this type of detoxification interaction is extremely rare in animals. Here, using laboratory behavioral assays and analyses of videotaped interactions in South America, we report widespread venom detoxification among ants in the subfamily Formicinae. Across both data sets, nine formicine species, representing all major clades, used a stereotyped grooming behavior to self-apply formic acid (acidopore grooming) in response to fire ant (Solenopsis invicta and S. saevissima) venom exposure. In laboratory assays, this behavior increased the survivorship of species following exposure to S. invicta venom. Species expressed the behavior when exposed to additional alkaloid venoms, including both compositionally similar piperidine venom of an additional fire ant species and the pyrrolidine/pyrroline alkaloid venom of a Monomorium species. In addition, species expressed the behavior following exposure to the uncharacterized venom of a Crematogaster species. However, species did not express acidopore grooming when confronted with protein-based ant venoms or when exposed to monoterpenoid-based venom. This pattern, combined with the specific chemistry of the reaction of formic acid with venom alkaloids, indicates that alkaloid venoms are targets of detoxification grooming. Solenopsis thief ants, and Monomorium species stand out as brood-predators of formicine ants that produce piperidine, pyrrolidine, and pyrroline venom, providing an important ecological context for the use of detoxification behavior. Detoxification behavior also represents a mechanism that can influence the order of assemblage dominance hierarchies surrounding food competition. Thus, this behavior likely influences ant-assemblages through a variety of ecological pathways.

  17. Modern trends in animal venom research - omics and nanomaterials

    PubMed Central

    Utkin, Yuri N

    2017-01-01

    Animal venom research is a specialized investigation field, in which a number of different methods are used and this array is constantly expanding. Thus, recently emerged omics and nanotechnologies have already been successfully applied to venom research. Animal venoms have been studied for quite a long time. The traditional reductionist approach has been to isolate individual toxins and then study their structure and function. Unfortunately, the characterization of the venom as a whole system and its multiple effects on an entire organism were not possible until recent times. The development of new methods in mass spectrometry and sequencing have allowed such characterizations of venom, encompassing the identification of new toxins present in venoms at extremely low concentrations to changes in metabolism of prey organisms after envenomation. In particular, this type of comprehensive research has become possible due to the development of the various omics technologies: Proteomics, peptidomics, transcriptomics, genomics and metabolomics. As in other research fields, these omics technologies ushered in a revolution for venom studies, which is now entering the era of big data. Nanotechnology is a very new branch of technology and developing at an extremely rapid pace. It has found application in many spheres and has not bypassed the venom studies. Nanomaterials are quite promising in medicine, and most studies combining venoms and nanomaterials are dedicated to medical applications. Conjugates of nanoparticles with venom components have been proposed for use as drugs or diagnostics. For example, nanoparticles conjugated with chlorotoxin - a toxin in scorpion venom, which has been shown to bind specifically to glioma cells - are considered as potential glioma-targeted drugs, and conjugates of neurotoxins with fluorescent semiconductor nanoparticles or quantum dots may be used to detect endogenous targets expressed in live cells. The data on application of omics and

  18. Snake venomics: from the inventory of toxins to biology.

    PubMed

    Calvete, Juan J

    2013-12-01

    A deep understanding of the composition of venoms and of the principles governing the evolution of venomous systems is of applied importance for exploring the enormous potential of venoms as sources of chemical and pharmacological novelty but also to fight the dire consequences of snakebite envenomings. This goal is now within the reach of "omic" technologies. A central thesis developed in this essay is the view that making sense of the huge inventory of data gathered through "omic" approaches requires the integration of this information across the biological system. Key to this is the identification of evolutionary and ecological trends; without the evolutionary link, systems venomics is relegated to a set of miscellaneous facts. The interplay between chance and adaptation plays a central role in the evolution of biological systems (Monod, 1970). However, the evolution of venomous species and their venoms do not always follow the same course, and the identification of structural and functional convergences and divergences among venoms is often unpredictable by a phylogenetic hypothesis. Toxins sharing a structural fold present in venoms from phylogenetically distant snakes often share antigenic determinants. The deficit of antivenom supply in certain regions of the world can be mitigated in part through the optimized use of existing antivenoms, and through the design of novel broad-range polyspecific antivenoms. Proteomics-guided identification of evolutionary and immunoreactivity trends among homologous and heterologous venoms may aid in the replacement of the traditional geographic- and phylogenetic-driven hypotheses for antivenom production strategies by a more rationale approach based on a hypothesis-driven systems venomics approach. Selected applications of venomics and antivenomics for exploring the chemical space and immunological profile of venoms will illustrate the author's views on the impact these proteomics tools may have in the field of toxinology

  19. Toxinology of venoms from five Australian lesser known elapid snakes.

    PubMed

    Pycroft, Kyle; Fry, Bryan G; Isbister, Geoffrey K; Kuruppu, Sanjaya; Lawrence, Josie; Ian Smith, A; Hodgson, Wayne C

    2012-10-01

    Research into Australian elapid venoms has mainly focused on the seven genera of greatest clinical significance: Acanthophis, Hoplocephalus, Notechis, Oxyuranus, Pseudechis, Pseudonaja and Tropidechis. However, even small species represent a potential for causing severe clinical envenoming. Further, owing to taxonomic distinctiveness, these species are a potential source of novel toxins for use in drug design and development. This is the first study to characterize the venoms of Cryptophis boschmai, Denisonia devisi, Echiopsis curta, Hemiaspis signata and Vermicella annulata. MALDI analysis of each venom, over the range of 4-40 kDa, indicated components in the weight range for three finger toxins (6-8 kDa) and phospholipase A(2) (PLA(2) ; 12-14 kDA). Interestingly, C. boschmai venom was the only venom, which contained components > 25 kDa. All venoms (10 μg/ml) demonstrated in vitro neurotoxicity in the chick biventer cervicis nerve-muscle preparation, with a relative rank order of: H. signata ≥ D. devisi ≥ V. annulata = E. curta > C. boschmai. CSL polyvalent antivenom neutralized the inhibitory effects of C. boschmai venom but only delayed the inhibitory effect of the other venoms. All venoms displayed PLA(2) activity but over a wide range (i.e. 1-621 μmol/min./mg). The venoms of C. boschmai (60 μg/kg, i.v.), D. devisi (60 μg/kg, i.v.) and H. signata (60 μg/kg, i.v.) produced hypotensive effects in vivo in an anaesthetized rat preparation. H. signata displayed moderate pro-coagulant activity while the other venoms were weakly pro-coagulant. This study demonstrated that these understudied Australian elapids have varying pharmacological activity, with notable in vitro neurotoxicity for four of the venoms, and may produce mild to moderate effects following systemic envenoming. © 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.

  20. Studies on Bee Venom and Its Medical Uses

    NASA Astrophysics Data System (ADS)

    Ali, Mahmoud Abdu Al-Samie Mohamed

    2012-07-01

    Use of honey and other bee products in human treatments traced back thousands of years and healing properties are included in many religious texts including the Veda, Bible and Quran. Apitherapy is the use of honey bee products for medical purposes, this include bee venom, raw honey, royal jelly, pollen, propolis, and beeswax. Whereas bee venom therapy is the use of live bee stings (or injectable venom) to treat various diseases such as arthritis, rheumatoid arthritis, multiple sclerosis (MS), lupus, sciatica, low back pain, and tennis elbow to name a few. It refers to any use of venom to assist the body in healing itself. Bee venom contains at least 18 pharmacologically active components including various enzymes, peptides and amines. Sulfur is believed to be the main element in inducing the release of cortisol from the adrenal glands and in protecting the body from infections. Contact with bee venom produces a complex cascade of reactions in the human body. The bee venom is safe for human treatments, the median lethal dose (LD50) for an adult human is 2.8 mg of venom per kg of body weight, i.e. a person weighing 60 kg has a 50% chance of surviving injections totaling 168 mg of bee venom. Assuming each bee injects all its venom and no stings are quickly removed at a maximum of 0.3 mg venom per sting, 560 stings could well be lethal for such a person. For a child weighing 10 kg, as little as 93.33 stings could be fatal. However, most human deaths result from one or few bee stings due to allergic reactions, heart failure or suffocation from swelling around the neck or the mouth. As compare with other human diseases, accidents and other unusual cases, the bee venom is very safe for human treatments.

  1. Proteomic identification of gender molecular markers in Bothrops jararaca venom.

    PubMed

    Zelanis, André; Menezes, Milene C; Kitano, Eduardo S; Liberato, Tarcísio; Tashima, Alexandre K; Pinto, Antonio F M; Sherman, Nicholas E; Ho, Paulo L; Fox, Jay W; Serrano, Solange M T

    2016-04-29

    Variation in the snake venom proteome is a well-documented phenomenon; however, sex-based variation in the venom proteome/peptidome is poorly understood. Bothrops jararaca shows significant sexual size dimorphism and here we report a comparative proteomic/peptidomic analysis of venoms from male and female specimens and correlate it with the evaluation of important venom features. We demonstrate that adult male and female venoms have distinct profiles of proteolytic activity upon fibrinogen and gelatin. These differences were clearly reflected in their different profiles of SDS-PAGE, two-dimensional electrophoresis and glycosylated proteins. Identification of differential protein bands and spots between male or female venoms revealed gender-specific molecular markers. However, the proteome comparison by in-solution trypsin digestion and label-free quantification analysis showed that the overall profiles of male and female venoms are similar at the polypeptide chain level but show striking variation regarding their attached carbohydrate moieties. The analysis of the peptidomes of male and female venoms revealed different contents of peptides, while the bradykinin potentiating peptides (BPPs) showed rather similar profiles. Furthermore we confirmed the ubiquitous presence of four BPPs that lack the C-terminal Q-I-P-P sequence only in the female venom as gender molecular markers. As a result of these studies we demonstrate that the sexual size dimorphism is associated with differences in the venom proteome/peptidome in B. jararaca species. Moreover, gender-based variations contributed by different glycosylation levels in toxins impact venom complexity. Bothrops jararaca is primarily a nocturnal and generalist snake species, however, it exhibits a notable ontogenetic shift in diet and in venom proteome upon neonate to adult transition. As is common in the Bothrops genus, B. jararaca shows significant sexual dimorphism in snout-vent length and weight, with females being

  2. Venom Proteins from Parasitoid Wasps and Their Biological Functions.

    PubMed

    Moreau, Sébastien J M; Asgari, Sassan

    2015-06-26

    Parasitoid wasps are valuable biological control agents that suppress their host populations. Factors introduced by the female wasp at parasitization play significant roles in facilitating successful development of the parasitoid larva either inside (endoparasitoid) or outside (ectoparasitoid) the host. Wasp venoms consist of a complex cocktail of proteinacious and non-proteinacious components that may offer agrichemicals as well as pharmaceutical components to improve pest management or health related disorders. Undesirably, the constituents of only a small number of wasp venoms are known. In this article, we review the latest research on venom from parasitoid wasps with an emphasis on their biological function, applications and new approaches used in venom studies.

  3. Novel transcripts in the maxillary venom glands of advanced snakes.

    PubMed

    Fry, Bryan G; Scheib, Holger; de L M Junqueira de Azevedo, Inacio; Silva, Debora Andrade; Casewell, Nicholas R

    2012-06-01

    Venom proteins are added to reptile venoms through duplication of a body protein gene, with the duplicate tissue-specifically expressed in the venom gland. Molecular scaffolds are recruited from a wide range of tissues and with a similar level of diversity of ancestral activity. Transcriptome studies have proven an effective and efficient tool for the discovery of novel toxin scaffolds. In this study, we applied venom gland transcriptomics to a wide taxonomical diversity of advanced snakes and recovered transcripts encoding three novel protein scaffold types lacking sequence homology to any previously characterised snake toxin type: lipocalin, phospholipase A2 (type IIE) and vitelline membrane outer layer protein. In addition, the first snake maxillary venom gland isoforms were sequenced of ribonuclease, which was only recently sequenced from lizard mandibular venom glands. Further, novel isoforms were also recovered for the only recently characterised veficolin toxin class also shared between lizard and snake venoms. The additional complexity of snake venoms has important implications not only for understanding their molecular evolution, but also reinforces the tremendous importance of venoms as a diverse bio-resource.

  4. Venomic and transcriptomic analysis of centipede Scolopendra subspinipes dehaani.

    PubMed

    Liu, Zi-Chao; Zhang, Rong; Zhao, Feng; Chen, Zhong-Ming; Liu, Hao-Wen; Wang, Yan-Jie; Jiang, Ping; Zhang, Yong; Wu, Ying; Ding, Jiu-Ping; Lee, Wen-Hui; Zhang, Yun

    2012-12-07

    Centipedes have venom glands in their first pair of limbs, and their venoms contain a large number of components with different biochemical and pharmacological properties. However, information about the compositions and functions of their venoms is largely unknown. In this study, Scolopendra subspinipes dehaani venoms were systematically investigated by transcriptomic and proteomic analysis coupled with biological function assays. After random screening approximately 1500 independent clones, 1122 full length cDNA sequences, which encode 543 different proteins, were cloned from a constructed cDNA library using a pair of venom glands from a single centipede species. Neurotoxins, ion channel acting components and venom allergens were the main fractions of the crude venom as revealed by transcriptomic analysis. Meanwhile, 40 proteins/peptides were purified and characterized from crude venom of S. subspinipes dehaani. The N-terminal amino acid sequencing and mass spectrum results of 29 out of these 40 proteins or peptides matched well with their corresponding cDNAs. The purified proteins/peptides showed different pharmacological properties, including the following: (1) platelet aggregating activity; (2) anticoagulant activity; (3) phospholipase A(2) activity; (4) trypsin inhibiting activity; (5) voltage-gated potassium channel activities; (6) voltage-gated sodium channel activities; (7) voltage-gated calcium channel activities. Most of them showed no significant similarity to other protein sequences deposited in the known public database. This work provides the largest number of protein or peptide candidates with medical-pharmaceutical significance and reveals the toxin nature of centipede S. subspinipes dehaani venom.

  5. Two families of antimicrobial peptides from wasp (Vespa magnifica) venom.

    PubMed

    Xu, Xueqing; Li, Jianxu; Lu, Qiuming; Yang, Hailong; Zhang, Yungong; Lai, Ren

    2006-02-01

    The hornet possesses highly toxic venom, which is rich in toxin, enzymes and biologically active peptides. Many bioactive substances were identified from wasp venom. Two families of antimicrobial peptides were purified and characterized from the venom of the wasp, Vespamagnifica (Smith). The primary structures of these peptides are homologous to those of chemotactic peptides and mastoparans isolated from other vespid venoms. They also share similarity to temporins which are amphibian antimicrobial peptides identified from the skin of the frog, Ranaboylii. These peptides show antimicrobial activities against bacteria and fungi. However, they show little hemolytic activity against human blood red cells.

  6. [Use of medicinal plants against scorpionic and ophidian venoms].

    PubMed

    Memmi, A; Sansa, G; Rjeibi, I; El Ayeb, M; Srairi-Abid, N; Bellasfer, Z; Fekhih, A

    2007-01-01

    The scorpionic and ophidian envenomations are a serious public health problem in Tunisia especially in Southeastern regions. In these regions Artemisia campestris L is a plant well known which has a very important place in traditional medicine for its effectiveness against alleged venom of scorpions and snakes. In this work, we tested for the first time, the anti-venomous activity of Artemisia campestris L against the scorpion Androctonus australis garzonii and the viper Macrovipera lebetina venoms. Assays were conducted by fixing the dose of extract to3 mg/mouse while doses of venom are variable. The leaves of Artemisia campestris L were extracted by various organic solvents (Ether of oil, ethyl acetate, methanol and ethanol) and each extract was tested for its venom neutralizing capacity. For the ethanolic extract, a significant activity with respect to the venoms of scorpion Androctonus australis garzonii (Aag), was detected. Similarly, a significant neutralizing activity against the venom of a viper Macrovipera lebetina (Ml), was obtained with the dichloromethane extract. These results suggest the presence of two different type of chemical components in this plant: those neutralizing the venom of scorpion are soluble in ethanol whereas those neutralizing the venom of viper are soluble in dichloromethane.

  7. Diversity of peptide toxins from stinging ant venoms.

    PubMed

    Aili, Samira R; Touchard, Axel; Escoubas, Pierre; Padula, Matthew P; Orivel, Jérôme; Dejean, Alain; Nicholson, Graham M

    2014-12-15

    Ants (Hymenoptera: Formicidae) represent a taxonomically diverse group of arthropods comprising nearly 13,000 extant species. Sixteen ant subfamilies have individuals that possess a stinger and use their venom for purposes such as a defence against predators, competitors and microbial pathogens, for predation, as well as for social communication. They exhibit a range of activities including antimicrobial, haemolytic, cytolytic, paralytic, insecticidal and pain-producing pharmacologies. While ant venoms are known to be rich in alkaloids and hydrocarbons, ant venoms rich in peptides are becoming more common, yet remain understudied. Recent advances in mass spectrometry techniques have begun to reveal the true complexity of ant venom peptide composition. In the few venoms explored thus far, most peptide toxins appear to occur as small polycationic linear toxins, with antibacterial properties and insecticidal activity. Unlike other venomous animals, a number of ant venoms also contain a range of homodimeric and heterodimeric peptides with one or two interchain disulfide bonds possessing pore-forming, allergenic and paralytic actions. However, ant venoms seem to have only a small number of monomeric disulfide-linked peptides. The present review details the structure and pharmacology of known ant venom peptide toxins and their potential as a source of novel bioinsecticides and therapeutic agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. PARASITOID VENOM INDUCES METABOLIC CASCADES IN FLY HOSTS

    PubMed Central

    Mrinalini; Siebert, Aisha L.; Wright, Jeremy; Martinson, Ellen; Wheeler, David; Werren, John H.

    2016-01-01

    Parasitoid wasps inject insect hosts with a cocktail of venoms to manipulate the physiology, development, and immunity of the hosts and to promote development of the parasitoid offspring. The jewel wasp Nasonia vitripennis is a model parasitoid with at least 79 venom proteins. We conducted a high-throughput analysis of Nasonia venom effects on temporal changes of 249 metabolites in pupae of the flesh fly host (Sarcophaga bullata), over a five-day time course. Our results show that venom does not simply arrest the metabolism of the fly host. Rather, it targets specific metabolic processes while keeping hosts alive for at least five days post venom injection by the wasp. We found that venom: (a) Activates the sorbitol biosynthetic pathway while maintaining stable glucose levels, (b) Causes a shift in intermediary metabolism by switching to anaerobic metabolism and blocking the tricarboxylic acid cycle, (c) Arrests chitin biosynthesis that likely reflects developmental arrest of adult fly structures, (d) Elevates the majority of free amino acids, and (e) May be increasing phospholipid degradation. Despite sharing some metabolic effects with cold treatment, diapause, and hypoxia, the venom response is distinct from these conditions. Because Nasonia venom dramatically increases sorbitol levels without changing glucose levels, it could be a useful model for studying the regulation of the sorbitol pathway, which is relevant to diabetes research. Our findings generally support the view that parasitoid venoms are a rich source of bioactive molecules with potential biomedical applications. PMID:27867325

  9. THE PHOTODYNAMIC ACTION OF EOSIN AND ERYTHROSIN UPON SNAKE VENOM

    PubMed Central

    Noguchi, Hideyo

    1906-01-01

    Since the hæmolysins of the several venoms respond differently to photodynamic action, they may be regarded as possessing different chemical constitutions. As regards stability, cobra hæmolysin ranks first, daboia second, and Crotalus third. The toxicity of all the venoms is more or less diminished by eosin and erythrosin in sunlight. This reduction in toxicity depends upon chemical changes, of more or less profound nature, taking place in certain of the active principles of the venom. The more stabile the predominant active principles the less the reduction in toxicity, and vice versa. Venom-neurotoxins are highly resistant to photodynamic action, venom-hæmolysins are less resistant, while the hæmorrhagin and thrombokinase of Crotalus and daboia venoms exhibit weak powers of resistance to their action. Hence it follows that while cobra venom remained almost unaltered, rattlesnake and daboia venoms were greatly reduced in toxicity when mixed with the fluorescent dyes and exposed to sunlight. There is an interesting parallel between the action of eosin and erythrosin upon the different venoms and their reactions to other injurious agencies. For example, the hæmolysins of cobra and daboia venoms are more heat resistant than the hæmolysin of Crotalus venom, and the former are less injured by the dyes than the latter. The neurotoxin of the former venoms is also more heat stabile than that of the rattlesnake, and the same relative degree of resistance holds for this substance and the anilines. Just as the hæmorrhagin of rattlesnake venom and the thrombokinase of daboia venom are destroyed by a temperature of 75° C., so are they readily inactivated by the photo dynamic substances employed. The globulin-precipitating and blood corpuscle-protecting principle of cobra venom is relatively thermostabile and in contradistinction to the immunity-precipitins it is also unaffected by eosin and erythrosin. This study of the action of photodynamic substances upon snake

  10. [Venom as a cure--some notes on ancient medicine].

    PubMed

    Teichfischer, Philipp

    2015-01-01

    Very little is known today about the linguistics and facts relating to venoms in the ancient world. The article concerns itself initially with the terminology: How were venoms conceptualized and what position did they occupy among medicines and other poisons? Additionally ancient knowledge of the constitution and location of the venoms will be examined. Furthermore, it shall be outlined how it was perceived that the poisons actually took effect. The results of our investigations indicate that it was unlikely that venoms were used for medicinal purposes in ancient times.

  11. Inactivation of complement by Loxosceles reclusa spider venom.

    PubMed

    Gebel, H M; Finke, J H; Elgert, K D; Cambell, B J; Barrett, J T

    1979-07-01

    Zymosan depletion of serum complement in guinea pigs rendered them highly resistant to lesion by Loxosceles reclusa spider venom. Guinea pigs deficient in C4 of the complement system are as sensitive to the venom as normal guinea pigs. The injection of 35 micrograms of whole recluse venom intradermally into guinea pigs lowered their complement level by 35.7%. Brown recluse spider venom in concentrations as slight as 0.02 micrograms protein/ml can totally inactivate one CH50 of guinea pig complement in vitro. Bee, scorpion, and other spider venoms had no influence on the hemolytic titer of complement. Fractionation of recluse spider venom by Sephadex G-200 filtration separated the complement-inactivating property of the venom into three major regions which could be distinguished on the basis of heat stability as well as size. None was neutralized by antivenom. Polyacrylamide gel electrophoresis of venom resolved the complement inactivators into five fractions. Complement inactivated by whole venom or the Sephadex fractions could be restored to hemolytic activity by supplements of fresh serum but not by heat-inactivated serum, pure C3, pure C5, or C3 and C5 in combination.

  12. Chemical Punch Packed in Venoms Makes Centipedes Excellent Predators*

    PubMed Central

    Yang, Shilong; Liu, Zhonghua; Xiao, Yao; Li, Yuan; Rong, Mingqiang; Liang, Songping; Zhang, Zhiye; Yu, Haining; King, Glenn F.; Lai, Ren

    2012-01-01

    Centipedes are excellent predatory arthropods that inject venom to kill or immobilize their prey. Although centipedes have long been known to be venomous, their venoms remain largely unexplored. The chemical components responsible for centipede predation and the functional mechanisms are unknown. Twenty-six neurotoxin-like peptides belonging to ten groups were identified from the centipede venoms, Scolopendra subspinipes mutilans L. Koch by peptidomics combined with transcriptome analysis, revealing the diversity of neurotoxins. These neurotoxins each contain two to four intramolecular disulfide bridges, and in most cases the disulfide framework is different from that found in neurotoxins from the venoms of spiders, scorpions, marine cone snails, sea anemones, and snakes (5S animals). Several neurotoxins contain potential insecticidal abilities, and they are found to act on voltage-gated sodium, potassium, and calcium channels, respectively. Although these neurotoxins are functionally similar to the disulfide-rich neurotoxins found in the venoms of 5S animals in that they modulate the activity of voltage-gated ion channels, in almost all cases the primary structures of the centipede venom peptides are unique. This represents an interesting case of convergent evolution in which different venomous animals have evolved different molecular strategies for targeting the same ion channels in prey and predators. Moreover, the high level of biochemical diversity revealed in this study suggests that centipede venoms might be attractive subjects for prospecting and screening for peptide candidates with potential pharmaceutical or agrochemical applications. PMID:22595790

  13. Venom Proteins from Parasitoid Wasps and Their Biological Functions

    PubMed Central

    Moreau, Sébastien J. M.; Asgari, Sassan

    2015-01-01

    Parasitoid wasps are valuable biological control agents that suppress their host populations. Factors introduced by the female wasp at parasitization play significant roles in facilitating successful development of the parasitoid larva either inside (endoparasitoid) or outside (ectoparasitoid) the host. Wasp venoms consist of a complex cocktail of proteinacious and non-proteinacious components that may offer agrichemicals as well as pharmaceutical components to improve pest management or health related disorders. Undesirably, the constituents of only a small number of wasp venoms are known. In this article, we review the latest research on venom from parasitoid wasps with an emphasis on their biological function, applications and new approaches used in venom studies. PMID:26131769

  14. Dynamic Rearrangement in Snake Venom Gland Proteome: Insights into Bothrops jararaca Intraspecific Venom Variation.

    PubMed

    Augusto-de-Oliveira, César; Stuginski, Daniel R; Kitano, Eduardo S; Andrade-Silva, Débora; Liberato, Tarcísio; Fukushima, Isabella; Serrano, Solange M T; Zelanis, André

    2016-10-07

    We carried out an analysis of the venom gland proteome of Bothrops jararaca taking into account two distinct phases of its ontogenetic development (i.e., newborn and adult) and the marked sexual dimorphism recently reported on its venom proteome. Proteomic data analysis showed a dynamic rearrangement in the proteome landscape of B. jararaca venom gland upon development and gender-related changes. Differentially expressed proteins covered a number of biological pathways related to protein synthesis, including proteins associated with transcription and translation, which were found to be significantly higher expressed in the newborn venom gland. Our results suggest that the variation in the expression levels of cellular proteins might give rise to an even higher variation in the levels of the expressed toxins. Upon aging, the venom gland proteome repertoire related to the protein synthesis together with ecological traits would have an impact on the toxin repertoire, which, in the case of B. jararaca species, would enable the species to deal with different prey types during its lifespan. Proteomic data are available via ProteomeXchange with identifier PXD004186.

  15. Coevolution of venom function and venom resistance in a rattlesnake predator and its squirrel prey

    PubMed Central

    Biardi, James E.; Gibbs, H. Lisle

    2016-01-01

    Measuring local adaptation can provide insights into how coevolution occurs between predators and prey. Specifically, theory predicts that local adaptation in functionally matched traits of predators and prey will not be detected when coevolution is governed by escalating arms races, whereas it will be present when coevolution occurs through an alternate mechanism of phenotype matching. Here, we analyse local adaptation in venom activity and prey resistance across 12 populations of Northern Pacific rattlesnakes and California ground squirrels, an interaction that has often been described as an arms race. Assays of venom function and squirrel resistance show substantial geographical variation (influenced by site elevation) in both venom metalloproteinase activity and resistance factor effectiveness. We demonstrate local adaptation in the effectiveness of rattlesnake venom to overcoming present squirrel resistance, suggesting that phenotype matching plays a role in the coevolution of these molecular traits. Further, the predator was the locally adapted antagonist in this interaction, arguing that rattlesnakes are evolutionarily ahead of their squirrel prey. Phenotype matching needs to be considered as an important mechanism influencing coevolution between venomous animals and resistant prey. PMID:27122552

  16. Protease Inhibitors from Marine Venomous Animals and Their Counterparts in Terrestrial Venomous Animals

    PubMed Central

    Mourão, Caroline B.F.; Schwartz, Elisabeth F.

    2013-01-01

    The Kunitz-type protease inhibitors are the best-characterized family of serine protease inhibitors, probably due to their abundance in several organisms. These inhibitors consist of a chain of ~60 amino acid residues stabilized by three disulfide bridges, and was first observed in the bovine pancreatic trypsin inhibitor (BPTI)-like protease inhibitors, which strongly inhibit trypsin and chymotrypsin. In this review we present the protease inhibitors (PIs) described to date from marine venomous animals, such as from sea anemone extracts and Conus venom, as well as their counterparts in terrestrial venomous animals, such as snakes, scorpions, spiders, Anurans, and Hymenopterans. More emphasis was given to the Kunitz-type inhibitors, once they are found in all these organisms. Their biological sources, specificity against different proteases, and other molecular blanks (being also K+ channel blockers) are presented, followed by their molecular diversity. Whereas sea anemone, snakes and other venomous animals present mainly Kunitz-type inhibitors, PIs from Anurans present the major variety in structure length and number of Cys residues, with at least six distinguishable classes. A representative alignment of PIs from these venomous animals shows that, despite eventual differences in Cys assignment, the key-residues for the protease inhibitory activity in all of them occupy similar positions in primary sequence. The key-residues for the K+ channel blocking activity was also compared. PMID:23771044

  17. Snake Venom Metalloproteinases and Their Peptide Inhibitors from Myanmar Russell’s Viper Venom

    PubMed Central

    Yee, Khin Than; Pitts, Morgan; Tongyoo, Pumipat; Rojnuckarin, Ponlapat; Wilkinson, Mark C.

    2016-01-01

    Russell’s viper bites are potentially fatal from severe bleeding, renal failure and capillary leakage. Snake venom metalloproteinases (SVMPs) are attributed to these effects. In addition to specific antivenom therapy, endogenous inhibitors from snakes are of interest in studies of new treatment modalities for neutralization of the effect of toxins. Two major snake venom metalloproteinases (SVMPs): RVV-X and Daborhagin were purified from Myanmar Russell’s viper venom using a new purification strategy. Using the Next Generation Sequencing (NGS) approach to explore the Myanmar RV venom gland transcriptome, mRNAs of novel tripeptide SVMP inhibitors (SVMPIs) were discovered. Two novel endogenous tripeptides, pERW and pEKW were identified and isolated from the crude venom. Both purified SVMPs showed caseinolytic activity. Additionally, RVV-X displayed specific proteolytic activity towards gelatin and Daborhagin showed potent fibrinogenolytic activity. These activities were inhibited by metal chelators. Notably, the synthetic peptide inhibitors, pERW and pEKW, completely inhibit the gelatinolytic and fibrinogenolytic activities of respective SVMPs at 5 mM concentration. These complete inhibitory effects suggest that these tripeptides deserve further study for development of a therapeutic candidate for Russell’s viper envenomation. PMID:28042812

  18. Coevolution of venom function and venom resistance in a rattlesnake predator and its squirrel prey.

    PubMed

    Holding, Matthew L; Biardi, James E; Gibbs, H Lisle

    2016-04-27

    Measuring local adaptation can provide insights into how coevolution occurs between predators and prey. Specifically, theory predicts that local adaptation in functionally matched traits of predators and prey will not be detected when coevolution is governed by escalating arms races, whereas it will be present when coevolution occurs through an alternate mechanism of phenotype matching. Here, we analyse local adaptation in venom activity and prey resistance across 12 populations of Northern Pacific rattlesnakes and California ground squirrels, an interaction that has often been described as an arms race. Assays of venom function and squirrel resistance show substantial geographical variation (influenced by site elevation) in both venom metalloproteinase activity and resistance factor effectiveness. We demonstrate local adaptation in the effectiveness of rattlesnake venom to overcoming present squirrel resistance, suggesting that phenotype matching plays a role in the coevolution of these molecular traits. Further, the predator was the locally adapted antagonist in this interaction, arguing that rattlesnakes are evolutionarily ahead of their squirrel prey. Phenotype matching needs to be considered as an important mechanism influencing coevolution between venomous animals and resistant prey. © 2016 The Author(s).

  19. Observations on white and yellow venoms from an individual southern Pacific rattlesnake (Crotalus viridis helleri).

    PubMed

    Johnson, E K; Kardong, K V; Ownby, C L

    1987-01-01

    Biochemical differences in white and yellow venoms produced in the separate venom glands of an individual southern Pacific rattlesnake (Crotalus viridis helleri) were investigated. Compared to the yellow venom, the white venom contained fewer low molecular weight components and was considerably less toxic. Although the exact LD50 was not determined, the white venom did not produce toxic effects in mice when injected i.v. at concentrations up to 10 mg/kg. The i.v. LD50 of the yellow venom was approximately 1.6 mg/kg. Both white and yellow venoms had hemorrhagic activity, but the white venom caused less intradermal hemorrhage in mice. No L-amino acid oxidase activity was measured in the white venom and protease and phospholipase A2 activities of the white venom were much less than in the yellow venom. The white and yellow venoms both produced myonecrosis at 1, 3 and 24 hr after i.m. injection into mice, however, there were some qualitative differences in the myonecrosis produced. When the venom samples were reacted against Wyeth's polyvalent (Crotalidae) antivenom using immunodiffusion, three precipitin bands formed against the yellow venom, whereas only one formed against the white venom. When reacted against an antiserum to myotoxin alpha from C. viridis viridis venom, both the white and yellow venoms produced one precipitin band each.

  20. Proteomic characterization of venom of the medically important Southeast Asian Naja sumatrana (Equatorial spitting cobra).

    PubMed

    Yap, Michelle Khai Khun; Fung, Shin Yee; Tan, Kae Yi; Tan, Nget Hong

    2014-05-01

    The proteome of Naja sumatrana (Equatorial spitting cobra) venom was investigated by shotgun analysis and a combination of ion-exchange chromatography and reverse phase HPLC. Shotgun analysis revealed the presence of 39 proteins in the venom while the chromatographic approach identified 37 venom proteins. The results indicated that, like other Asiatic cobra venoms, N. sumatrana contains large number of three finger toxins and phospholipases A2, which together constitute 92.1% by weight of venom protein. However, only eight of the toxins can be considered as major venom toxins. These include two phospholipases A2, three neurotoxins (two long neurotoxins and a short neurotoxin) and three cardiotoxins. The eight major toxins have relative abundance of 1.6-27.2% venom proteins and together account for 89.8% (by weight) of total venom protein. Other venom proteins identified include Zn-metalloproteinase-disintegrin, Thaicobrin, CRISP, natriuretic peptide, complement depleting factors, cobra venom factors, venom nerve growth factor and cobra serum albumin. The proteome of N. sumatrana venom is similar to proteome of other Asiatic cobra venoms but differs from that of African spitting cobra venom. Our results confirm that the main toxic action of N. sumatrana venom is neurotoxic but the large amount of cardiotoxins and phospholipases A2 are likely to contribute significantly to the overall pathophysiological action of the venom. The differences in toxin distribution between N. sumatrana venom and African spitting cobra venoms suggest possible differences in the pathophysiological actions of N. sumatrana venom and the African spitting cobra venoms, and explain why antivenom raised against Asiatic cobra venom is not effective against African spitting cobra venoms. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. 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.

    PubMed

    Lomonte, Bruno; Pla, Davinia; Sasa, Mahmood; Tsai, Wan-Chih; Solórzano, Alejandro; Ureña-Díaz, Juan Manuel; Fernández-Montes, María Laura; Mora-Obando, Diana; Sanz, Libia; Gutiérrez, José María; Calvete, Juan J

    2014-05-30

    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 A2 (PLA2), 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 PLA2 (~20%) and a group of three isoforms of CRISPs (~9%). Whereas isolated pelamitoxin was highly lethal to mice, neither the PLA2 nor the CRISP fraction caused death. However, the PLA2 rapidly increased plasma creatine kinase activity after intramuscular injection, indicating its myotoxic action. Differing from myotoxic PLA2s of viperids, this PLA2 was not cytolytic to murine myogenic cells in vitro, suggesting possible differences in its mechanism of action. The median lethal dose (LD50) 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

  2. The unusual toxicity and stability properties of crude venom from isolated nematocysts of Pelagia noctiluca (Cnidaria, Scyphozoa).

    PubMed

    Marino, A; Crupi, R; Rizzo, G; Morabito, R; Musci, G; La Spada, G

    2007-09-17

    We have firstly investigated the toxicological activity by hemolytic assay of crude extract obtained by sonication of holotrichous isorhiza isolated nematocysts of the Scyphozoan Pelagia noctiluca, collected in the Strait of Messina. The hemolytic activity was both time- and dose-dependent on fish, rabbit, chicken and human red blood cells. At lowest doses rabbit and chicken erythrocytes were the most sensitive, whereas those of eel were the most resistant to the crude extract. Different storage conditions, such as -20 degrees C, -80 degrees C for up to 6 months and lyophilization, did not affect the stability of crude venom. Moreover, neither treatment at 4 degrees C, 20 degrees C and 37 degrees C for different time periods ranging between 30 min and 24 h, nor harsh thermal treatment at 80 degrees C and 100 degrees C affected the hemolytic power. The crude venom resulted even stable towards proteolysis and alkaline pH values.

  3. Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using omega-conotoxin from Conus magus venom

    SciTech Connect

    Olivera, B.M.; Cruz, L.J.; de Santos, V.; LeCheminant, G.W.; Griffin, D.; Zeikus, R.; McIntosh, M.; Galyean, R.; Varga, J.; Gray, W.R.; Rivier, J.

    1987-04-21

    The omega-conotoxins from the venom of fish-hunting cone snails are probably the most useful of presently available ligands for neuronal Ca channels from vertebrates. Two of these peptide toxins, omega-conotoxins MVIIA and MVIIB from the venom of Conus magus, were purified. The amino acid sequences show significant differences from omega-conotoxins from Conus geographus. Total synthesis of omega-conotoxin MVIIA was achieved, and biologically active radiolabeled toxin was produced by iodination. Although omega-conotoxins from C. geographus (GVIA) and C. magus (MVIIA) appear to compete for the same sites in mammalian brain, in amphibian brain the high-affinity binding of omega-conotoxin MVIIA has narrower specificity. In this system, it is demonstrated that a combination of two omega-conotoxins can be used for biochemically defining receptor subtypes and suggested that these correspond to subtypes of neutronal Ca/sup 2 +/ channels.

  4. Two novel antimicrobial peptides from centipede venoms.

    PubMed

    Peng, Kanfu; Kong, Yi; Zhai, Lei; Wu, Xiongfei; Jia, Peng; Liu, Jingze; Yu, Haining

    2010-01-01

    Centipede venoms are complex mixtures of biochemically and pharmacologically active components such as peptides and proteins. Very few are known about their pharmacological actions. The present work reports the structural and functional characterization of two antimicrobial peptides (scolopin 1 and -2) identified from centipede venoms of Scolopendra subspinipes mutilans by Sephadex gel filtration and reverse-phase high-performance liquid chromatography (RP-HPLC). The amino acid sequences of scolopin 1 and -2 were FLPKMSTKLRVPYRRGTKDYH and GILKKFMLHRGTKVYKMRTLSKRSH determined by Edman degradation and matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Both scolopin 1 and -2 showed strong antimicrobial activities against tested microorganisms including Gram-positive/negative bacteria and fungi. They also showed moderate hemolytic activity against both human and rabbit red cells. This is the first report of antimicrobial peptides from centipedes.

  5. Effects of gamma radiation on snake venoms

    NASA Astrophysics Data System (ADS)

    Nascimento, N.; Spencer, P. J.; Andrade, H. F.; Guarnieri, M. C.; Rogero, J. R.

    1998-06-01

    Ionizing radiation is able to detoxify several venoms, including snake venoms, without affecting significantly their immunogenic properties. Inn order to elucidate this phenomena, we conceived a comparative pharmacological study between native and irradiated (2,000 Gy) crotoxin, the main toxin of the South American rattlesnake Crotalus durissus terrificus. Crotoxin was isolated and purified by molecular exclusion chromatography, pI precipitation and, susbequentely submitted to irradiaiton. Gel filtration of the irradiated toxin resulted in some high molecular weight aggregates formation. Crotoxin toxicity decreased two folds after irradiation, as determined by LD 50 in mice. Native and irradiated crotoxin biodistribution ocured in the same general manner, with renal elimination. However, in contrast to irradiated crotoxin, the native form was initially retained in kidneys. A later concentration (2-3 hr) appeared in phagocytic mononuclear cells rich organs (liver and spleen) and neural junction rich organs (muscle and brain).

  6. Characterization of the gila monster (Heloderma suspectum suspectum) venom proteome.

    PubMed

    Sanggaard, Kristian W; Dyrlund, Thomas F; Thomsen, Line R; Nielsen, Tania A; Brøndum, Lars; Wang, Tobias; Thøgersen, Ida B; Enghild, Jan J

    2015-03-18

    The archetypical venomous lizard species are the helodermatids, the gila monsters (Heloderma suspectum) and the beaded lizards (Heloderma horridum). In the present study, the gila monster venom proteome was characterized using 2D-gel electrophoresis and tandem mass spectrometry-based de novo peptide sequencing followed by protein identification based on sequence homology. A total of 39 different proteins were identified out of the 58 selected spots that represent the major constituents of venom. Of these proteins, 19 have not previously been identified in helodermatid venom. The data showed that helodermatid venom is complex and that this complexity is caused by genetic isoforms and post-translational modifications including proteolytic processing. In addition, the venom proteome analysis revealed that the major constituents of the gila monster venom are kallikrein-like serine proteinases (EC 3.4.21) and phospholipase A2 (type III) enzymes (EC 3.1.1.4). A neuroendocrine convertase 1 homolog that most likely converts the proforms of the previously identified bioactive exendins into the mature and active forms was identified suggesting that these peptide toxins are secreted as proforms that are activated by proteolytic cleavage following secretion as opposed to being activated intracellularly. The presented global protein identification-analysis provides the first overview of the helodermatid venom composition. The helodermatid lizards are the classical venomous lizards, and the pharmacological potential of the venom from these species has been known for years; best illustrated by the identification of exendin-4, which is now used in the treatment of type 2 diabetes. Despite the potential, no global analyses of the protein components in the venom exist. A hindrance is the lack of a genome sequence because it prevents protein identification using a conventional approach where MS data are searched against predicted protein sequences based on the genome sequence

  7. Functional and Structural Diversification of the Anguimorpha Lizard Venom System*

    PubMed Central

    Fry, Bryan G.; Winter, Kelly; Norman, Janette A.; Roelants, Kim; Nabuurs, Rob J. A.; van Osch, Matthias J. P.; Teeuwisse, Wouter M.; van der Weerd, Louise; Mcnaughtan, Judith E.; Kwok, Hang Fai; Scheib, Holger; Greisman, Laura; Kochva, Elazar; Miller, Laurence J.; Gao, Fan; Karas, John; Scanlon, Denis; Lin, Feng; Kuruppu, Sanjaya; Shaw, Chris; Wong, Lily; Hodgson, Wayne C.

    2010-01-01

    Venom has only been recently discovered to be a basal trait of the Anguimorpha lizards. Consequently, very little is known about the timings of toxin recruitment events, venom protein molecular evolution, or even the relative physical diversifications of the venom system itself. A multidisciplinary approach was used to examine the evolution across the full taxonomical range of this ∼130 million-year-old clade. Analysis of cDNA libraries revealed complex venom transcriptomes. Most notably, three new cardioactive peptide toxin types were discovered (celestoxin, cholecystokinin, and YY peptides). The latter two represent additional examples of convergent use of genes in toxic arsenals, both having previously been documented as components of frog skin defensive chemical secretions. Two other novel venom gland-overexpressed modified versions of other protein frameworks were also recovered from the libraries (epididymal secretory protein and ribonuclease). Lectin, hyaluronidase, and veficolin toxin types were sequenced for the first time from lizard venoms and shown to be homologous to the snake venom forms. In contrast, phylogenetic analyses demonstrated that the lizard natriuretic peptide toxins were recruited independently of the form in snake venoms. The de novo evolution of helokinestatin peptide toxin encoding domains within the lizard venom natriuretic gene was revealed to be exclusive to the helodermatid/anguid subclade. New isoforms were sequenced for cysteine-rich secretory protein, kallikrein, and phospholipase A2 toxins. Venom gland morphological analysis revealed extensive evolutionary tinkering. Anguid glands are characterized by thin capsules and mixed glands, serous at the bottom of the lobule and mucous toward the apex. Twice, independently this arrangement was segregated into specialized serous protein-secreting glands with thick capsules with the mucous lobules now distinct (Heloderma and the Lanthanotus/Varanus clade). The results obtained highlight

  8. Functional and structural diversification of the Anguimorpha lizard venom system.

    PubMed

    Fry, Bryan G; Winter, Kelly; Norman, Janette A; Roelants, Kim; Nabuurs, Rob J A; van Osch, Matthias J P; Teeuwisse, Wouter M; van der Weerd, Louise; McNaughtan, Judith E; Kwok, Hang Fai; Scheib, Holger; Greisman, Laura; Kochva, Elazar; Miller, Laurence J; Gao, Fan; Karas, John; Scanlon, Denis; Lin, Feng; Kuruppu, Sanjaya; Shaw, Chris; Wong, Lily; Hodgson, Wayne C

    2010-11-01

    Venom has only been recently discovered to be a basal trait of the Anguimorpha lizards. Consequently, very little is known about the timings of toxin recruitment events, venom protein molecular evolution, or even the relative physical diversifications of the venom system itself. A multidisciplinary approach was used to examine the evolution across the full taxonomical range of this ∼130 million-year-old clade. Analysis of cDNA libraries revealed complex venom transcriptomes. Most notably, three new cardioactive peptide toxin types were discovered (celestoxin, cholecystokinin, and YY peptides). The latter two represent additional examples of convergent use of genes in toxic arsenals, both having previously been documented as components of frog skin defensive chemical secretions. Two other novel venom gland-overexpressed modified versions of other protein frameworks were also recovered from the libraries (epididymal secretory protein and ribonuclease). Lectin, hyaluronidase, and veficolin toxin types were sequenced for the first time from lizard venoms and shown to be homologous to the snake venom forms. In contrast, phylogenetic analyses demonstrated that the lizard natriuretic peptide toxins were recruited independently of the form in snake venoms. The de novo evolution of helokinestatin peptide toxin encoding domains within the lizard venom natriuretic gene was revealed to be exclusive to the helodermatid/anguid subclade. New isoforms were sequenced for cysteine-rich secretory protein, kallikrein, and phospholipase A(2) toxins. Venom gland morphological analysis revealed extensive evolutionary tinkering. Anguid glands are characterized by thin capsules and mixed glands, serous at the bottom of the lobule and mucous toward the apex. Twice, independently this arrangement was segregated into specialized serous protein-secreting glands with thick capsules with the mucous lobules now distinct (Heloderma and the Lanthanotus/Varanus clade). The results obtained

  9. Peptidomic and transcriptomic profiling of four distinct spider venoms.

    PubMed

    Oldrati, Vera; Koua, Dominique; Allard, Pierre-Marie; Hulo, Nicolas; Arrell, Miriam; Nentwig, Wolfgang; Lisacek, Frédérique; Wolfender, Jean-Luc; Kuhn-Nentwig, Lucia; Stöcklin, Reto

    2017-01-01

    Venom based research is exploited to find novel candidates for the development of innovative pharmacological tools, drug candidates and new ingredients for cosmetic and agrochemical industries. Moreover, venomics, as a well-established approach in systems biology, helps to elucidate the genetic mechanisms of the production of such a great molecular biodiversity. Today the advances made in the proteomics, transcriptomics and bioinformatics fields, favor venomics, allowing the in depth study of complex matrices and the elucidation even of minor compounds present in minute biological samples. The present study illustrates a rapid and efficient method developed for the elucidation of venom composition based on NextGen mRNA sequencing of venom glands and LC-MS/MS venom proteome profiling. The analysis of the comprehensive data obtained was focused on cysteine rich peptide toxins from four spider species originating from phylogenetically distant families for comparison purposes. The studied species were Heteropoda davidbowie (Sparassidae), Poecilotheria formosa (Theraphosidae), Viridasius fasciatus (Viridasiidae) and Latrodectus mactans (Theridiidae). This led to a high resolution profiling of 284 characterized cysteine rich peptides, 111 of which belong to the Inhibitor Cysteine Knot (ICK) structural motif. The analysis of H. davidbowie venom revealed a high richness in term of venom diversity: 95 peptide sequences were identified; out of these, 32 peptides presented the ICK structural motif and could be classified in six distinct families. The profiling of P. formosa venom highlighted the presence of 126 peptide sequences, with 52 ICK toxins belonging to three structural distinct families. V. fasciatus venom was shown to contain 49 peptide sequences, out of which 22 presented the ICK structural motif and were attributed to five families. The venom of L. mactans, until now studied for its large neurotoxins (Latrotoxins), revealed the presence of 14 cysteine rich

  10. Whole Transcriptome of the Venom Gland from Urodacus yaschenkoi Scorpion

    PubMed Central

    Juárez-González, Víctor Rivelino; Possani, Lourival D.

    2015-01-01

    Australian scorpion venoms have been poorly studied, probably because they do not pose an evident threat to humans. In addition, the continent has other medically important venomous animals capable of causing serious health problems. Urodacus yaschenkoi belongs to the most widely distributed family of Australian scorpions (Urodacidae) and it is found all over the continent, making it a useful model system for studying venom composition and evolution. This communication reports the whole set of mRNA transcripts produced by the venom gland. U. yaschenkoi venom is as complex as its overseas counterparts. These transcripts certainly code for several components similar to known scorpion venom components, such as: alpha-KTxs, beta-KTxs, calcins, protease inhibitors, antimicrobial peptides, sodium-channel toxins, toxin-like peptides, allergens, La1-like, hyaluronidases, ribosomal proteins, proteasome components and proteins related to cellular processes. A comparison with the venom gland transcriptome of Centruroides noxius (Buthidae) showed that these two scorpions have similar components related to biological processes, although important differences occur among the venom toxins. In contrast, a comparison with sequences reported for Urodacus manicatus revealed that these two Urodacidae species possess the same subfamily of scorpion toxins. A comparison with sequences of an U. yaschenkoi cDNA library previously reported by our group showed that both techniques are reliable for the description of the venom components, but the whole transcriptome generated with Next Generation Sequencing platform provides sequences of all transcripts expressed. Several of which were identified in the proteome, but many more transcripts were identified including uncommon transcripts. The information reported here constitutes a reference for non-Buthidae scorpion venoms, providing a comprehensive view of genes that are involved in venom production. Further, this work identifies new putative

  11. Whole Transcriptome of the Venom Gland from Urodacus yaschenkoi Scorpion.

    PubMed

    Luna-Ramírez, Karen; Quintero-Hernández, Verónica; Juárez-González, Víctor Rivelino; Possani, Lourival D

    2015-01-01

    Australian scorpion venoms have been poorly studied, probably because they do not pose an evident threat to humans. In addition, the continent has other medically important venomous animals capable of causing serious health problems. Urodacus yaschenkoi belongs to the most widely distributed family of Australian scorpions (Urodacidae) and it is found all over the continent, making it a useful model system for studying venom composition and evolution. This communication reports the whole set of mRNA transcripts produced by the venom gland. U. yaschenkoi venom is as complex as its overseas counterparts. These transcripts certainly code for several components similar to known scorpion venom components, such as: alpha-KTxs, beta-KTxs, calcins, protease inhibitors, antimicrobial peptides, sodium-channel toxins, toxin-like peptides, allergens, La1-like, hyaluronidases, ribosomal proteins, proteasome components and proteins related to cellular processes. A comparison with the venom gland transcriptome of Centruroides noxius (Buthidae) showed that these two scorpions have similar components related to biological processes, although important differences occur among the venom toxins. In contrast, a comparison with sequences reported for Urodacus manicatus revealed that these two Urodacidae species possess the same subfamily of scorpion toxins. A comparison with sequences of an U. yaschenkoi cDNA library previously reported by our group showed that both techniques are reliable for the description of the venom components, but the whole transcriptome generated with Next Generation Sequencing platform provides sequences of all transcripts expressed. Several of which were identified in the proteome, but many more transcripts were identified including uncommon transcripts. The information reported here constitutes a reference for non-Buthidae scorpion venoms, providing a comprehensive view of genes that are involved in venom production. Further, this work identifies new putative

  12. Pro-inflammatory activities in elapid snake venoms.

    PubMed Central

    Tambourgi, D. V.; dos Santos, M. C.; Furtado, M. de F.; de Freitas, M. C.; da Silva, W. D.; Kipnis, T. L.

    1994-01-01

    1. Snake venoms from the genera Micrurus (M. ibiboboca and M. spixii) and Naja (N. naja, N. melanoleuca and N. nigricollis) were analysed, using biological and immunochemical methods, to detect pro-inflammatory activities, cobra venom factor (COF), proteolytic enzymes, thrombin-like substances, haemorrhagic and oedema-producing substances. 2. The venoms of the five snake species activate the complement system (C) in normal human serum (NHS) in a dose-related fashion, at concentrations ranging from 5 micrograms to 200 micrograms ml-1 serum. Electrophoretic conversion of C3 was observed with all venoms in NHS containing normal concentrations of Ca2+ and Mg2+, but only by venoms from N. naja and N. melanoleuca when Ca2+ was chelated by adding Mg(2+)-EGTA. 3. Purified human C3 was electrophoretically converted, in the absence of other C components, by the venoms from N. naja, N. nigricollis and M. ibiboboca. However, only the venoms from N. naja and N. melanoleuca contained a 144 kDa protein revealed in Western blot with sera against COF or human C3. 4. All venoms, at minimum concentrations of 30 ng ml-1, were capable of lysing sheep red blood cells, also in a dose-related fashion, when incubated with these cells in presence of egg yolk as a source of lecithin. Although the venoms from M. spixii and N. nigricollis showed detectable thrombin-like activity, these and the other venoms were free of proteolytic activity when fibrin, gelatin and casein, were used as substrates. 5. When tested on mice skin, all five venoms were capable of inducing an increase in vascular permeability and oedema, but were devoid of haemorrhagic producing substances (haemorrhagins).(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 2 Figure 3 Figure 4 PMID:7921595

  13. Fish Allergy

    MedlinePlus

    ... can react to touching fish or breathing in vapors from cooking fish. A fish allergy can cause ... hives red spots swelling a drop in blood pressure , causing lightheadedness or loss of consciousness Your child ...

  14. City Fishing.

    ERIC Educational Resources Information Center

    Lange, Robert E.

    1979-01-01

    A program of supplying opportunities for fishing at locations within and near urban areas was developed. This effort included stocking, management of bodies of water for fishing, and presentation of fishing clinics for urban fishermen. (RE)

  15. Fish Hearing.

    ERIC Educational Resources Information Center

    Blaxter, J. H. S.

    1980-01-01

    Provides related information about hearing in fish, including the sensory stimulus of sound in the underwater environment, mechanoreceptors in fish, pressure perception and the swimbladder, specializations in sound conduction peculiar to certain fish families. Includes numerous figures. (CS)

  16. Comparative study of anticoagulant and procoagulant properties of 28 snake venoms from families Elapidae, Viperidae, and purified Russell's viper venom-factor X activator (RVV-X).

    PubMed

    Suntravat, Montamas; Nuchprayoon, Issarang; Pérez, John C

    2010-09-15

    Snake venoms consist of numerous molecules with diverse biological functions used for capturing prey. Each component of venom has a specific target, and alters the biological function of its target. Once these molecules are identified, characterized, and cloned; they could have medical applications. The activated clotting time (ACT) and clot rate were used for screening procoagulant and anticoagulant properties of 28 snake venoms. Crude venoms from Daboia russellii siamensis, Bothrops asper, Bothrops moojeni, and one Crotalus oreganus helleri from Wrightwood, CA, had procoagulant activity. These venoms induced a significant shortening of the ACT and showed a significant increase in the clot rate when compared to the negative control. Factor X activator activity was also measured in 28 venoms, and D. r. siamensis venom was 5-6 times higher than those of B. asper, B. moojeni, and C. o. helleri from Wrightwood County. Russell's viper venom-factor X activator (RVV-X) was purified from D. r. siamensis venom, and then procoagulant activity was evaluated by the ACT and clot rate. Other venoms, Crotalus atrox and two Naja pallida, had anticoagulant activity. A significant increase in the ACT and a significant decrease in the clot rate were observed after the addition of these venoms; therefore, the venoms were considered to have anticoagulant activity. Venoms from the same species did not always have the same ACT and clot rate profiles, but the profiles were an excellent way to identify procoagulant and anticoagulant activities in snake venoms.

  17. Specific immunotherapy using Hymenoptera venom: systematic review.

    PubMed

    Watanabe, Alexandra Sayuri; Fonseca, Luiz Augusto Marcondes; Galvão, Clóvis Eduardo Santos; Kalil, Jorge; Castro, Fabio Fernandes Morato

    2010-01-01

    The only effective treatment for patients who have severe reactions after Hymenoptera stings is venom immunotherapy. The aim of this study was to review the literature to assess the effects of venom immunotherapy among patients presenting severe reactions after Hymenoptera stings. Randomized controlled trials in the worldwide literature were reviewed. The manuscript was produced in the Discipline of Allergy and Clinical Immunology, Universidade de São Paulo (USP). Randomized controlled trials involving venom immunotherapy versus placebo or only patient follow-up were evaluated. The risk of systemic reactions after specific immunotherapy was evaluated by calculating odds ratios (OR) and their 95% confidence intervals. 2,273 abstracts were identified by the keywords search. Only four studies were included in this review. The chi-square test for heterogeneity showed that two studies were homogeneous and could be included in a meta-analysis. By combining the two studies, the odds ratio became significant: 0.29 (0.10-0.87). However, analysis on the severity of the reactions after immunotherapy showed that the benefits may not be so significant because the reactions were mostly similar to or milder than the original reaction. Specific immunotherapy should be recommended for adults and children with moderate to severe reactions, but there is no need to prescribe it for children with skin reactions alone, especially if the exposure is very sporadic. On the other hand, the risk-benefit relation should always be assessed in each case.

  18. Chem I Supplement: Bee Sting: The Chemistry of an Insect Venom.

    ERIC Educational Resources Information Center

    O'Connor, Rod; Peck, Larry

    1980-01-01

    Considers various aspects of bee stings including the physical mechanism of the venom apparatus in the bee, categorization of physiological responses of nonprotected individuals to bee sting, chemical composition of bee venom and the mechanisms of venom action, and areas of interest in the synthesis of bee venom. (CS)

  19. Detection of Snake Venom in Post-Antivenom Samples by Dissociation Treatment Followed by Enzyme Immunoassay

    PubMed Central

    Maduwage, Kalana P.; O’Leary, Margaret A.; Silva, Anjana; Isbister, Geoffrey K.

    2016-01-01

    Venom detection is crucial for confirmation of envenomation and snake type in snake-bite patients. Enzyme immunoassay (EIA) is used to detect venom, but antivenom in samples prevents venom detection. We aimed to detect snake venom in post-antivenom samples after dissociating venom-antivenom complexes with glycine-HCl (pH 2.2) and heating for 30 min at 950 °C. Serum samples underwent dissociation treatment and then Russell’s viper venom or Australian elapid venom measured by EIA. In confirmed Russell’s viper bites with venom detected pre-antivenom (positive controls), no venom was detected in untreated post-antivenom samples, but was after dissociation treatment. In 104 non-envenomed patients (negative controls), no venom was detected after dissociation treatment. In suspected Russell’s viper bites, ten patients with no pre-antivenom samples had venom detected in post-antivenom samples after dissociation treatment. In 20 patients with no venom detected pre-antivenom, 13 had venom detected post-antivenom after dissociation treatment. In another 85 suspected Russell’s viper bites with no venom detected pre-antivenom, 50 had venom detected after dissociation treatment. Dissociation treatment was also successful for Australian snake envenomation including taipan, mulga, tiger snake and brown snake. Snake venom can be detected by EIA in post-antivenom samples after dissociation treatment allowing confirmation of diagnosis of envenomation post-antivenom. PMID:27136587

  20. Chem I Supplement: Bee Sting: The Chemistry of an Insect Venom.

    ERIC Educational Resources Information Center

    O'Connor, Rod; Peck, Larry

    1980-01-01

    Considers various aspects of bee stings including the physical mechanism of the venom apparatus in the bee, categorization of physiological responses of nonprotected individuals to bee sting, chemical composition of bee venom and the mechanisms of venom action, and areas of interest in the synthesis of bee venom. (CS)

  1. Single venom-based immunotherapy effectively protects patients with double positive tests to honey bee and Vespula venom

    PubMed Central

    2013-01-01

    Background Referring to individuals with reactivity to honey bee and Vespula venom in diagnostic tests, the umbrella terms “double sensitization” or “double positivity” cover patients with true clinical double allergy and those allergic to a single venom with asymptomatic sensitization to the other. There is no international consensus on whether immunotherapy regimens should generally include both venoms in double sensitized patients. Objective We investigated the long-term outcome of single venom-based immunotherapy with regard to potential risk factors for treatment failure and specifically compared the risk of relapse in mono sensitized and double sensitized patients. Methods Re-sting data were obtained from 635 patients who had completed at least 3 years of immunotherapy between 1988 and 2008. The adequate venom for immunotherapy was selected using an algorithm based on clinical details and the results of diagnostic tests. Results Of 635 patients, 351 (55.3%) were double sensitized to both venoms. The overall re-exposure rate to Hymenoptera stings during and after immunotherapy was 62.4%; the relapse rate was 7.1% (6.0% in mono sensitized, 7.8% in double sensitized patients). Recurring anaphylaxis was statistically less severe than the index sting reaction (P = 0.004). Double sensitization was not significantly related to relapsing anaphylaxis (P = 0.56), but there was a tendency towards an increased risk of relapse in a subgroup of patients with equal reactivity to both venoms in diagnostic tests (P = 0.15). Conclusions Single venom-based immunotherapy over 3 to 5 years effectively and long-lastingly protects the vast majority of both mono sensitized and double sensitized Hymenoptera venom allergic patients. Double venom immunotherapy is indicated in clinically double allergic patients reporting systemic reactions to stings of both Hymenoptera and in those with equal reactivity to both venoms in diagnostic tests who have not reliably identified the

  2. Proteomic characterization of the venom and transcriptomic analysis of the venomous gland from the Mexican centipede Scolopendra viridis.

    PubMed

    González-Morales, Lidia; Pedraza-Escalona, Martha; Diego-Garcia, Elia; Restano-Cassulini, Rita; Batista, Cesar V F; Gutiérrez, Maria del Carmen; Possani, Lourival D

    2014-12-05

    This communication reports the results of proteomic, transcriptomic, biochemical and electrophysiological analysis of the soluble venom and venom glands of the Mexican centipede Scolopendra viridis Say (here thereafter abbreviated S. viridis). Separation of the soluble venom permitted to obtain 54 different fractions, from which a mass finger printing analysis permitted the identification of at least 86 components, where 70% of the molecules have low molecular masses. Two-dimensional electrophoretic separation of this venom revealed the presence of about forty proteins with molecular weights ranging from 17 to 58kDa. The novo sequencing of 149 peptides obtained by LC-MS/MS from the 2D-gels showed the presence of proteins with amino acid sequences similar to several enzymes and venom allergens type 3. Furthermore, a total of 180 sequences were obtained from a cDNA library prepared with two venomous glands. From this, 155 sequences correspond to complete genes containing more than 200 base pairs each. Comparative sequence analyses of these sequences indicated the presence of different types of enzymes and toxin-like genes. Two proteins with molecular weights around 37,000 and 42,000Da were shown to contain hyaluronidase activity. Electrophysiological assays performed with soluble venom show that it decreases mammalian sodium channel currents. Animal venoms of Scolopendra species have been scarcely studied, although they have been reported to contain several bioactive compounds, some of which with potential therapeutic interest. The Mexican centipede S. viridis contains a powerful venom, capable of inflicting immediate effects on their preys. This communication is focused on the identification and description of a proteomic and transcriptomic analysis of the protein components of this venom. Several amino acid sequences similar to reported enzymes are the principal components in the S. viridis venom, but also a low number of toxins were identified. This knowledge

  3. Region-specific neutralization of Indian cobra (Naja naja) venom by polyclonal antibody raised against the eastern regional venom: A comparative study of the venoms from three different geographical distributions.

    PubMed

    Shashidharamurthy, R; Kemparaju, K

    2007-01-01

    Indian cobra (Naja naja) venoms from different geographical locations vary in their composition, biochemical, and pharmacological properties. Venom samples from eastern, western and southern India are compared in this study. The venom from eastern region was found to be the most lethal of the three regional venoms. Monovalent antivenom (NNEV-IgG) prepared against the eastern venom was found to cross-react with the other two regional venoms. NNEV-IgG at an Ag:Ab ratio of 1:25 completely neutralized the lethality of eastern venom. At this ratio, it did not neutralize the other two venoms, but the survival time of experimental mice was extended significantly. Commercially available polyvalent antivenom neutralized the lethality of western venom at an Ag:Ab ratio of 1:60 and increased the survival time of experimental mice injected with eastern and southern venoms marginally. Further, NNEV-IgG neutralized the tested pharmacological and enzymatic activities of all the three venom samples dose dependently, with neutralization potency varying with the geographic origin of the tested venoms. Thus, the present study demonstrates the diversity in the immunological properties of venom from different geographical regions and underscores the importance of developing region-specific antivenoms for therapeutic purpose.

  4. Analysis of scorpion venom composition by Raman Spectroscopy

    NASA Astrophysics Data System (ADS)

    Martínez-Zérega, Brenda E.; González-Solís, José L.

    2015-01-01

    In this work we study the venom of two Centruroides scorpion species using Raman spectroscopy. The spectra analysis allows to determine the venoms chemical composition and to establish the main differences and similarities among the species. It is also shown that the use of Principal Component Analysis may help to tell apart between the scorpion species.

  5. 21 CFR 864.8950 - Russell viper venom reagent.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Russell viper venom reagent. 864.8950 Section 864.8950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8950 Russell viper venom...

  6. 21 CFR 864.8950 - Russell viper venom reagent.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Russell viper venom reagent. 864.8950 Section 864.8950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8950 Russell viper venom...

  7. 21 CFR 864.8950 - Russell viper venom reagent.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Russell viper venom reagent. 864.8950 Section 864.8950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8950 Russell viper venom...

  8. 21 CFR 864.8950 - Russell viper venom reagent.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Russell viper venom reagent. 864.8950 Section 864.8950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8950 Russell viper venom...

  9. Recent Advances in Research on Widow Spider Venoms and Toxins

    PubMed Central

    Yan, Shuai; Wang, Xianchun

    2015-01-01

    Widow spiders have received much attention due to the frequently reported human and animal injures caused by them. Elucidation of the molecular composition and action mechanism of the venoms and toxins has vast implications in the treatment of latrodectism and in the neurobiology and pharmaceutical research. In recent years, the studies of the widow spider venoms and the venom toxins, particularly the α-latrotoxin, have achieved many new advances; however, the mechanism of action of the venom toxins has not been completely clear. The widow spider is different from many other venomous animals in that it has toxic components not only in the venom glands but also in other parts of the adult spider body, newborn spiderlings, and even the eggs. More recently, the molecular basis for the toxicity outside the venom glands has been systematically investigated, with four proteinaceous toxic components being purified and preliminarily characterized, which has expanded our understanding of the widow spider toxins. This review presents a glance at the recent advances in the study on the venoms and toxins from the Latrodectus species. PMID:26633495

  10. Differential toxicity and venom gland gene expression in Centruroides vittatus.

    PubMed

    McElroy, Thomas; McReynolds, C Neal; Gulledge, Alyssa; Knight, Kelci R; Smith, Whitney E; Albrecht, Eric A

    2017-01-01

    Variation in venom toxicity and composition exists in many species. In this study, venom potency and venom gland gene expression was evaluated in Centruroides vittatus, size class I-II (immature) and size class IV (adults/penultimate instars) size classes. Venom toxicity was evaluated by probit analysis and returned ED50 values of 50.1 μg/g for class IV compared to 134.2 μg/g for class I-II 24 hours post injection, suggesting size class IV was 2.7 fold more potent. Next generation sequencing (NGS and qPCR were used to characterize venom gland gene expression. NGS data was assembled into 36,795 contigs, and annotated using BLASTx with UNIPROT. EdgeR analysis of the sequences showed statistically significant differential expression in transcripts associated with sodium and potassium channel modulation. Sodium channel modulator expression generally favored size class IV; in contrast, potassium channel modulators were favored in size class I-II expression. Real-time quantitative PCR of 14 venom toxin transcripts detected relative expression ratios that paralleled NGS data and identified potential family members or splice variants for several sodium channel modulators. Our data suggests ontogenetic differences in venom potency and venom related genes expression exist between size classes I-II and IV.

  11. Venom gland components of the ectoparasitoid wasp, Anisopteromalus calandrae

    USDA-ARS?s Scientific Manuscript database

    The wasp Anisopteromalus calandrae is a small ectoparasitoid that attacks stored product pest beetle larvae that develop inside grain kernels, and is thus a potential insect control tool. The components of the venom have not been studied, but venom peptides from other organisms have been identified ...

  12. Antimicrobial peptides from the venoms of Vespa bicolor Fabricius.

    PubMed

    Chen, Wenhu; Yang, Xinbo; Yang, Xiaolong; Zhai, Lei; Lu, Zekuan; Liu, Jingze; Yu, Haining

    2008-11-01

    Hornets possess highly toxic venoms, which are rich in toxins, enzymes and biologically active peptides. Many bioactive substances have been identified from wasp venoms. Vespa mastoparan (MP-VBs) and Vespa chemotatic peptide presenting antimicrobial action (VESP-VBs) were purified and characterized from the venom of the wasp, Vespa bicolor Fabricius. The precursors encoding VESP-VBs and MP-VBs were cloned from the cDNA library of the venomous glands. Analyzed by FAB-MS, the amino acid sequence and molecular mass for VESP-VB1 were FMPIIGRLMSGSL and 1420.6, for MP-VB1 were INMKASAAVAKKLL and 1456.5, respectively. The primary structures of these peptides are homologous to those of chemotactic peptides and mastoparans isolated from other vespid venoms. These peptides showed strong antimicrobial activities against bacteria and fungi and induced mast cell degranulation, but displayed almost no hemolytic activity towards human blood red cells.

  13. Scorpion venom components as potential candidates for drug development.

    PubMed

    Ortiz, Ernesto; Gurrola, Georgina B; Schwartz, Elisabeth Ferroni; Possani, Lourival D

    2015-01-01

    Scorpions are well known for their dangerous stings that can result in severe consequences for human beings, including death. Neurotoxins present in their venoms are responsible for their toxicity. Due to their medical relevance, toxins have been the driving force in the scorpion natural compounds research field. On the other hand, for thousands of years, scorpions and their venoms have been applied in traditional medicine, mainly in Asia and Africa. With the remarkable growth in the number of characterized scorpion venom components, several drug candidates have been found with the potential to tackle many of the emerging global medical threats. Scorpions have become a valuable source of biologically active molecules, from novel antibiotics to potential anticancer therapeutics. Other venom components have drawn attention as useful scaffolds for the development of drugs. This review summarizes the most promising candidates for drug development that have been isolated from scorpion venoms.

  14. Snake Venom: Any Clue for Antibiotics and CAM?

    PubMed Central

    2005-01-01

    Lately several naturally occurring peptides presenting antimicrobial activity have been described in the literature. However, snake venoms, which are an enormous source of peptides, have not been fully explored for searching such molecules. The aim of this work is to review the basis of antimicrobial mechanisms revealing snake venom as a feasible source for searching an antibiotic prototype. Therefore, it includes (i) a description of the constituents of the snake venoms involved in their main biological effects during the envenomation process; (ii) examples of snake venom molecules of commercial use; (iii) mechanisms of action of known antibiotics; and (iv) how the microorganisms can be resistant to antibiotics. This review also shows that snake venoms are not totally unexplored sources for antibiotics and complementary and alternative medicine (CAM). PMID:15841277

  15. Antibacterial activity of the venom of Heterometrus xanthopus

    PubMed Central

    Ahmed, Umair; Mujaddad-ur-Rehman, Malik; Khalid, Nauman; Fawad, Sardar Atiq; Fatima, Anees

    2012-01-01

    Heterometrus xanthopus (Scorpion) is one of the most venomous and ancient arthropods. Its venom contains anti-microbial peptides like hadrurin, scorpine, Pandinin 1, and Pandinin 2 that are able to effectively kill multidrug-resistant pathogens. The present study was conducted to evaluate the anti-bacterial activity of H. xanthopus venom. Six Gram-positive and Gram-negative bacterial strains were tested against 1/100, 1/10, and 1/1 fractions of distilled water diluted and crude venom. 1/100 and 1/10 dilutions were not successful in any of the six bacterial strains studied while the 1/1 dilution was effective on Bacillus subtilis ATCC 6633, Salmonella typhimurium ATCC 14028, and Pseudomonas aeruginosa ATCC 27853 with highest zone of inhibition were obtained on B. subtilis. Crude venom was effective against Enterococcus faecalis ATCC 14506, B. subtilis, S. typhimurium, and P. aeruginosa. The most effective results were observed on B. subtilis. PMID:23087515

  16. Antibacterial activity of the venom of Heterometrus xanthopus.

    PubMed

    Ahmed, Umair; Mujaddad-Ur-Rehman, Malik; Khalid, Nauman; Fawad, Sardar Atiq; Fatima, Anees

    2012-01-01

    Heterometrus xanthopus (Scorpion) is one of the most venomous and ancient arthropods. Its venom contains anti-microbial peptides like hadrurin, scorpine, Pandinin 1, and Pandinin 2 that are able to effectively kill multidrug-resistant pathogens. The present study was conducted to evaluate the anti-bacterial activity of H. xanthopus venom. Six Gram-positive and Gram-negative bacterial strains were tested against 1/100, 1/10, and 1/1 fractions of distilled water diluted and crude venom. 1/100 and 1/10 dilutions were not successful in any of the six bacterial strains studied while the 1/1 dilution was effective on Bacillus subtilis ATCC 6633, Salmonella typhimurium ATCC 14028, and Pseudomonas aeruginosa ATCC 27853 with highest zone of inhibition were obtained on B. subtilis. Crude venom was effective against Enterococcus faecalis ATCC 14506, B. subtilis, S. typhimurium, and P. aeruginosa. The most effective results were observed on B. subtilis.

  17. Therapeutic potential of snake venom in cancer therapy: current perspectives.

    PubMed

    Vyas, Vivek Kumar; Brahmbhatt, Keyur; Bhatt, Hardik; Parmar, Utsav

    2013-02-01

    Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer. Snake venom toxins contributed significantly to the treatment of many medical conditions. There are many published studies describing and elucidating the anti-cancer potential of snake venom. Cancer therapy is one of the main areas for the use of protein peptides and enzymes originating from animals of different species. Some of these proteins or peptides and enzymes from snake venom when isolated and evaluated may bind specifically to cancer cell membranes, affecting the migration and proliferation of these cells. Some of substances found in the snake venom present a great potential as anti-tumor agent. In this review, we presented the main results of recent years of research involving the active compounds of snake venom that have anticancer activity.

  18. Brown spider (Loxosceles genus) venom toxins: tools for biological purposes.

    PubMed

    Chaim, Olga Meiri; Trevisan-Silva, Dilza; Chaves-Moreira, Daniele; Wille, Ana Carolina M; Ferrer, Valéria Pereira; Matsubara, Fernando Hitomi; Mangili, Oldemir Carlos; da Silveira, Rafael Bertoni; Gremski, Luiza Helena; Gremski, Waldemiro; Senff-Ribeiro, Andrea; Veiga, Silvio Sanches

    2011-03-01

    Venomous animals use their venoms as tools for defense or predation. These venoms are complex mixtures, mainly enriched of proteic toxins or peptides with several, and different, biological activities. In general, spider venom is rich in biologically active molecules that are useful in experimental protocols for pharmacology, biochemistry, cell biology and immunology, as well as putative tools for biotechnology and industries. Spider venoms have recently garnered much attention from several research groups worldwide. Brown spider (Loxosceles genus) venom is enriched in low molecular mass proteins (5-40 kDa). Although their venom is produced in minute volumes (a few microliters), and contain only tens of micrograms of protein, the use of techniques based on molecular biology and proteomic analysis has afforded rational projects in the area and permitted the discovery and identification of a great number of novel toxins. The brown spider phospholipase-D family is undoubtedly the most investigated and characterized, although other important toxins, such as low molecular mass insecticidal peptides, metalloproteases and hyaluronidases have also been identified and featured in literature. The molecular pathways of the action of these toxins have been reported and brought new insights in the field of biotechnology. Herein, we shall see how recent reports describing discoveries in the area of brown spider venom have expanded biotechnological uses of molecules identified in these venoms, with special emphasis on the construction of a cDNA library for venom glands, transcriptome analysis, proteomic projects, recombinant expression of different proteic toxins, and finally structural descriptions based on crystallography of toxins.

  19. Integrative Approach Reveals Composition of Endoparasitoid Wasp Venoms

    PubMed Central

    Mobley, James A.; Bowersock, Gregory J.; Taylor, James; Schlenke, Todd A.

    2013-01-01

    The fruit fly Drosophila melanogaster and its endoparasitoid wasps are a developing model system for interactions between host immune responses and parasite virulence mechanisms. In this system, wasps use diverse venom cocktails to suppress the conserved fly cellular encapsulation response. Although numerous genetic tools allow detailed characterization of fly immune genes, lack of wasp genomic information has hindered characterization of the parasite side of the interaction. Here, we use high-throughput nucleic acid and amino acid sequencing methods to describe the venoms of two related Drosophila endoparasitoids with distinct infection strategies, Leptopilina boulardi and L. heterotoma. Using RNA-seq, we assembled and quantified libraries of transcript sequences from female wasp abdomens. Next, we used mass spectrometry to sequence peptides derived from dissected venom gland lumens. We then mapped the peptide spectral data against the abdomen transcriptomes to identify a set of putative venom genes for each wasp species. Our approach captured the three venom genes previously characterized in L. boulardi by traditional cDNA cloning methods as well as numerous new venom genes that were subsequently validated by a combination of RT-PCR, blast comparisons, and secretion signal sequence search. Overall, 129 proteins were found to comprise L. boulardi venom and 176 proteins were found to comprise L. heterotoma venom. We found significant overlap in L. boulardi and L. heterotoma venom composition but also distinct differences that may underlie their unique infection strategies. Our joint transcriptomic-proteomic approach for endoparasitoid wasp venoms is generally applicable to identification of functional protein subsets from any non-genome sequenced organism. PMID:23717546

  20. Preparation of a novel antivenom against Atractaspis and Walterinnesia venoms.

    PubMed

    Ismail, M; Al-Ahaidib, M S; Abdoon, N; Abd-Elsalam, M A

    2007-01-01

    The two deadly snakes, Walterinnesia aegyptia (black desert cobra) and Atractaspis microlepidota (mole viper) share a common habitat in the central, eastern and western provinces of Saudi Arabia. Bites by either snake were characterized by rapid death, sometimes before reaching any medical facility. Confusing reports of "a black snake bite" are frequently found. The NAVPC had succeeded in preparing a highly effective antivenom against W. aegyptia venom which is now available in the market, but no antivenom against Atractaspis venom is found worldwide. This is probably because of the low molecular weight of sarafotoxins in the venom and hence their poor antigenic properties. At the NAVPC, sarafotoxins were separated by sequential gel filtration of A. microlepidota venom, while toxin T(III) of W. aegyptia venom obtained by cation exchange chromatography and gel filtration. Conjugation of the two toxins was carried out using glutaraldehyde in a two-step procedure followed by exhaustive dialysis. The conjugate was utilized to hyperimmunize 3-years old horses for 10 months, applying a low-dosage protocol and immunostimulants; the crude venoms of both snakes being added during the last 2 months. The F(ab')2 fraction of the antivenom was obtained by pH-guided salt precipitation, enzyme digestion and tangential desalting and filtration. The bivalent antivenom obtained protected mice and rats against the lethal effects of both venoms and rescued the rats challenged with lethal doses of the venoms in recovery experiments. It also neutralized the haemorrhagic, necrotizing and the cardiotoxic effects of A. microlepidota venom and the neuromuscular blocking effect of W. aegyptia venom. The antivenom offers a good rescue potential to those who are bitten by "a black snake" in Saudi Arabia.

  1. Effect of suramin on myotoxicity of some crotalid snake venoms.

    PubMed

    Arruda, E Z; Silva, N M V; Moraes, R A M; Melo, P A

    2002-06-01

    We investigated the protective effect of suramin, an enzyme inhibitor and an uncoupler of G protein from receptors, on the myotoxic activity in mice of different crotalid snake venoms (A.c. laticinctus, C.v. viridis, C.d. terrificus, B. jararacussu, B. moojeni, B. alternatus, B. jararaca, L. muta). Myotoxicity was evaluated in vivo by injecting im the venoms (0.5 or 1.0 mg/kg) dissolved in physiological saline solution (0.1 ml) and measuring plasma creatine kinase (CK) activity. Two experimental approaches were used in mice (N = 5 for each group). In protocol A, 1 mg of each venom was incubated with 1.0 mg suramin (15 min, 37 degrees C, in vitro), and then injected im into the mice at a dose of 1.0 mg/kg (in vivo). In protocol B, venoms, 1.0 mg/kg, were injected im 15 min prior to suramin (1.0 mg/kg, iv). Before and 2 h after the im injection blood was collected by orbital puncture. Plasma was separated and stored at 4 degrees C for determination of CK activity using a diagnostic kit from Sigma. Preincubation of some venoms (C.v. viridis, A.c. laticinctus, C.d. terrificus and B. jararacussu) with suramin reduced (37-76%) the increase in plasma CK, except for B. alternatus, B. jararaca or L. muta venoms. Injection of suramin after the venom partially protected (34-51%) against the myotoxicity of B. jararacussu, A.c. laticinctus and C.d. terrificus venom, and did not protect against C.v. viridis, L. muta, B. moojeni, B. alternatus or B. jararaca venoms. These results show that suramin has an antimyotoxic effect against some, but not all the North and South American crotalid snake venoms studied here.

  2. Virocidal activity of Egyptian scorpion venoms against hepatitis C virus.

    PubMed

    El-Bitar, Alaa M H; Sarhan, Moustafa M H; Aoki, Chie; Takahara, Yusuke; Komoto, Mari; Deng, Lin; Moustafa, Mohsen A; Hotta, Hak

    2015-03-24

    Hepatitis C virus (HCV) is a major global health problem, causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Development of well-tolerated regimens with high cure rates and fewer side effects is still much needed. Recently, natural antimicrobial peptides (AMPs) are attracting more attention as biological compounds and can be a good template to develop therapeutic agents, including antiviral agents against a variety of viruses. Various AMPs have been characterized from the venom of different venomous animals including scorpions. The possible antiviral activities of crude venoms obtained from five Egyptian scorpion species (Leiurus quinquestriatus, Androctonus amoreuxi, A. australis, A. bicolor and Scorpio maurus palmatus) were evaluated by a cell culture method using Huh7.5 cells and the J6/JFH1-P47 strain of HCV. Time-of-addition experiments and inactivation of enzymatic activities of the venoms were carried out to determine the characteristics of the anti-HCV activities. S. maurus palmatus and A. australis venoms showed anti-HCV activities, with 50% inhibitory concentrations (IC₅₀) being 6.3 ± 1.6 and 88.3 ± 5.8 μg/ml, respectively. S. maurus palmatus venom (30 μg/ml) impaired HCV infectivity in culture medium, but not inside the cells, through virocidal effect. The anti-HCV activity of this venom was not inhibited by a metalloprotease inhibitor or heating at 60°C. The antiviral activity was directed preferentially against HCV. S. maurus palmatus venom is considered as a good natural source for characterization and development of novel anti-HCV agents targeting the entry step. To our knowledge, this is the first report describing antiviral activities of Egyptian scorpion venoms against HCV, and may open a new approach towards discovering antiviral compounds derived from scorpion venoms.

  3. Analgesic effect of Persian Gulf Conus textile venom

    PubMed Central

    Tabaraki, Nasim; Shahbazzadeh, Delavar; Moradi, Ali Mashinchian; Vosughi, Gholamhossein; Mostafavi, Pargol Ghavam

    2014-01-01

    Objective(s): Cone snails are estimated to consist of up to 700 species. The venom of these snails has yielded a rich source of novel peptides. This study was aimed to study the analgesic effect of Persian Gulf Conus textile and its comparison with morphine in mouse model. Materials and Methods: Samples were collected in Larak Island. The venom ducts were Isolated and kept on ice then homogenized. The mixture centrifuged at 10000 × g for 20 min. Supernatant was considered as extracted venom. The protein profile of venom determined using 15% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Venom was administered intraperitoneally (IP) to evaluate the LD50 in Swiss albino mice. Different concentrations of Conus textile venom were injected intrathecally to mice to evaluate their analgesic effect in comparison to morphine. Injection was carried out between the L5 and L6 vertebrae. Differences between groups in the first and second phase were tested with Two-Way analysis of variance (ANOVA). Results: SDS-PAGE indicated 12 bands ranged between 6 and 180 KDa. Finally, ten ng of Conus crude venom showed the best analgesic activity in formalin test. No death observed up to 100 mg/kg. Analgesic activity of crude venom was more significant (P<0.05) in acute pain than inflammatory pain. The analgesic effect of 10 ng Conus venom was the same as morphine for reduction of inflammatory pain (P=0.27). Conclusion: The venom of Persian Gulf Conus textile contains an analgesic component for reliving of acute pain which can lead to find an analgesic drug. PMID:25729549

  4. Integrative approach reveals composition of endoparasitoid wasp venoms.

    PubMed

    Goecks, Jeremy; Mortimer, Nathan T; Mobley, James A; Bowersock, Gregory J; Taylor, James; Schlenke, Todd A

    2013-01-01

    The fruit fly Drosophila melanogaster and its endoparasitoid wasps are a developing model system for interactions between host immune responses and parasite virulence mechanisms. In this system, wasps use diverse venom cocktails to suppress the conserved fly cellular encapsulation response. Although numerous genetic tools allow detailed characterization of fly immune genes, lack of wasp genomic information has hindered characterization of the parasite side of the interaction. Here, we use high-throughput nucleic acid and amino acid sequencing methods to describe the venoms of two related Drosophila endoparasitoids with distinct infection strategies, Leptopilina boulardi and L. heterotoma. Using RNA-seq, we assembled and quantified libraries of transcript sequences from female wasp abdomens. Next, we used mass spectrometry to sequence peptides derived from dissected venom gland lumens. We then mapped the peptide spectral data against the abdomen transcriptomes to identify a set of putative venom genes for each wasp species. Our approach captured the three venom genes previously characterized in L. boulardi by traditional cDNA cloning methods as well as numerous new venom genes that were subsequently validated by a combination of RT-PCR, blast comparisons, and secretion signal sequence search. Overall, 129 proteins were found to comprise L. boulardi venom and 176 proteins were found to comprise L. heterotoma venom. We found significant overlap in L. boulardi and L. heterotoma venom composition but also distinct differences that may underlie their unique infection strategies. Our joint transcriptomic-proteomic approach for endoparasitoid wasp venoms is generally applicable to identification of functional protein subsets from any non-genome sequenced organism.

  5. Brown Spider (Loxosceles genus) Venom Toxins: Tools for Biological Purposes

    PubMed Central

    Chaim, Olga Meiri; Trevisan-Silva, Dilza; Chaves-Moreira, Daniele; Wille, Ana Carolina M.; Ferrer, Valéria Pereira; Matsubara, Fernando Hitomi; Mangili, Oldemir Carlos; da Silveira, Rafael Bertoni; Gremski, Luiza Helena; Gremski, Waldemiro; Senff-Ribeiro, Andrea; Veiga, Silvio Sanches

    2011-01-01

    Venomous animals use their venoms as tools for defense or predation. These venoms are complex mixtures, mainly enriched of proteic toxins or peptides with several, and different, biological activities. In general, spider venom is rich in biologically active molecules that are useful in experimental protocols for pharmacology, biochemistry, cell biology and immunology, as well as putative tools for biotechnology and industries. Spider venoms have recently garnered much attention from several research groups worldwide. Brown spider (Loxosceles genus) venom is enriched in low molecular mass proteins (5–40 kDa). Although their venom is produced in minute volumes (a few microliters), and contain only tens of micrograms of protein, the use of techniques based on molecular biology and proteomic analysis has afforded rational projects in the area and permitted the discovery and identification of a great number of novel toxins. The brown spider phospholipase-D family is undoubtedly the most investigated and characterized, although other important toxins, such as low molecular mass insecticidal peptides, metalloproteases and hyaluronidases have also been identified and featured in literature. The molecular pathways of the action of these toxins have been reported and brought new insights in the field of biotechnology. Herein, we shall see how recent reports describing discoveries in the area of brown spider venom have expanded biotechnological uses of molecules identified in these venoms, with special emphasis on the construction of a cDNA library for venom glands, transcriptome analysis, proteomic projects, recombinant expression of different proteic toxins, and finally structural descriptions based on crystallography of toxins. PMID:22069711

  6. The genesis of an exceptionally lethal venom in the timber rattlesnake (Crotalus horridus) revealed through comparative venom-gland transcriptomics

    PubMed Central

    2013-01-01

    Background Snake venoms generally show sequence and quantitative variation within and between species, but some rattlesnakes have undergone exceptionally rapid, dramatic shifts in the composition, lethality, and pharmacological effects of their venoms. Such shifts have occurred within species, most notably in Mojave (Crotalus scutulatus), South American (C. durissus), and timber (C. horridus) rattlesnakes, resulting in some populations with extremely potent, neurotoxic venoms without the hemorrhagic effects typical of rattlesnake bites. Results To better understand the evolutionary changes that resulted in the potent venom of a population of C. horridus from northern Florida, we sequenced the venom-gland transcriptome of an animal from this population for comparison with the previously described transcriptome of the eastern diamondback rattlesnake (C. adamanteus), a congener with a more typical rattlesnake venom. Relative to the toxin transcription of C. adamanteus, which consisted primarily of snake-venom metalloproteinases, C-type lectins, snake-venom serine proteinases, and myotoxin-A, the toxin transcription of C. horridus was far simpler in composition and consisted almost entirely of snake-venom serine proteinases, phospholipases A2, and bradykinin-potentiating and C-type natriuretic peptides. Crotalus horridus lacked significant expression of the hemorrhagic snake-venom metalloproteinases and C-type lectins. Evolution of shared toxin families involved differential expansion and loss of toxin clades within each species and pronounced differences in the highly expressed toxin paralogs. Toxin genes showed significantly higher rates of nonsynonymous substitution than nontoxin genes. The expression patterns of nontoxin genes were conserved between species, despite the vast differences in toxin expression. Conclusions Our results represent the first complete, sequence-based comparison between the venoms of closely related snake species and reveal in unprecedented

  7. The First Venomous Crustacean Revealed by Transcriptomics and Functional Morphology: Remipede Venom Glands Express a Unique Toxin Cocktail Dominated by Enzymes and a Neurotoxin

    PubMed Central

    von Reumont, Björn M.; Blanke, Alexander; Richter, Sandy; Alvarez, Fernando; Bleidorn, Christoph; Jenner, Ronald A.

    2014-01-01

    Animal venoms have evolved many times. Venomous species are especially common in three of the four main groups of arthropods (Chelicerata, Myriapoda, and Hexapoda), which together represent tens of thousands of species of venomous spiders, scorpions, centipedes, and hymenopterans. Surprisingly, despite their great diversity of body plans, there is no unambiguous evidence that any crustacean is venomous. We provide the first conclusive evidence that the aquatic, blind, and cave-dwelling remipede crustaceans are venomous and that venoms evolved in all four major arthropod groups. We produced a three-dimensional reconstruction of the venom delivery apparatus of the remipede Speleonectes tulumensis, showing that remipedes can inject venom in a controlled manner. A transcriptomic profile of its venom glands shows that they express a unique cocktail of transcripts coding for known venom toxins, including a diversity of enzymes and a probable paralytic neurotoxin very similar to one described from spider venom. We screened a transcriptomic library obtained from whole animals and identified a nontoxin paralog of the remipede neurotoxin that is not expressed in the venom glands. This allowed us to reconstruct its probable evolutionary origin and underlines the importance of incorporating data derived from nonvenom gland tissue to elucidate the evolution of candidate venom proteins. This first glimpse into the venom of a crustacean and primitively aquatic arthropod reveals conspicuous differences from the venoms of other predatory arthropods such as centipedes, scorpions, and spiders and contributes valuable information for ultimately disentangling the many factors shaping the biology and evolution of venoms and venomous species. PMID:24132120

  8. Biological activities of Peristrophe bivalvis extracts: promising potential for anti-snake venoms against Naja kaouthia and Trimeresurus albolabris venoms.

    PubMed

    Phaopongthai, Jatuporn; Noiphrom, Jureeporn; Phaopongthai, Supat; Pakmanee, Narumol; Sichaem, Jirapast

    2016-01-01

    This study evaluates the in vitro anti-snake venom potential of Peristrophe bivalvis (PB) extracts against Naja kaouthia (NK) and Trimeresurus albolabris (TA) venoms, including inhibition of cytotoxic effects and enzymatic activities, and the binding-precipitation of extracts and venom proteins analysis. In addition, the antioxidant, cytotoxic and in vivo acute oral toxic activities of PB extracts are also reported. The in vitro cytotoxic and enzymatic analysis reveals that the ethanol extracts of stems and leaves of PB showed good anti-snake venom activity against NK and TA venoms. In addition, the antioxidant result indicated that only the ethanol extract of leaves exhibited weak DPPH radical-scavenging activity. The ethanol whole-plant extract of PB also showed no cytotoxicity against four cell lines. Moreover, the in vivo acute oral toxicity result of the ethanol whole-plant extract showed that all treated rats did not exhibit abnormal toxic signs or deaths.

  9. Ontogenesis, gender, and molting influence the venom yield in the spider Coremiocnemis tropix (Araneae, Theraphosidae)

    PubMed Central

    Herzig, Volker

    2010-01-01

    The demand for spider venom increases along with the growing popularity of venoms-based research. A deeper understanding of factors that influence the venom yield in spiders would therefore be of interest to both commercial venom suppliers and research facilities. The present study addresses the influence of several factors on the venom yield by systematically analyzing the data obtained from 1773 electrical milkings of the Australian theraphosid spider Coremiocnemis tropix. Gender and ontogenesis were found to cause a major effect on the venom yield, as adult female C. tropix yielded significantly more venom than adult males. During ontogenesis, the venom yield increased with increasing size of the spiders. Furthermore, a significant reduction in the venom yield during the 50-day time interval preceding a molt was found. On the other hand, extended milking intervals (up to 449 days) and different states of nutrition (as an indication of how well the spider was fed) did not significantly affect the venom yield. Overall, the present findings suggest that venom production in spiders is carefully balanced between the demand for venom and the energy costs associated with its production. It can therefore be concluded that, in line with the venom optimization hypothesis, venom is a precious resource for spiders, which have implemented control mechanisms to ensure economical venom production and usage. PMID:21544186

  10. Deep venomics reveals the mechanism for expanded peptide diversity in cone snail venom.

    PubMed

    Dutertre, Sébastien; Jin, Ai-hua; Kaas, Quentin; Jones, Alun; Alewood, Paul F; Lewis, Richard J

    2013-02-01

    Cone snails produce highly complex venom comprising mostly small biologically active peptides known as conotoxins or conopeptides. Early estimates that suggested 50-200 venom peptides are produced per species have been recently increased at least 10-fold using advanced mass spectrometry. To uncover the mechanism(s) responsible for generating this impressive diversity, we used an integrated approach combining second-generation transcriptome sequencing with high sensitivity proteomics. From the venom gland transcriptome of Conus marmoreus, a total of 105 conopeptide precursor sequences from 13 gene superfamilies were identified. Over 60% of these precursors belonged to the three gene superfamilies O1, T, and M, consistent with their high levels of expression, which suggests these conotoxins play an important role in prey capture and/or defense. Seven gene superfamilies not previously identified in C. marmoreus, including five novel superfamilies, were also discovered. To confirm the expression of toxins identified at the transcript level, the injected venom of C. marmoreus was comprehensively analyzed by mass spectrometry, revealing 2710 and 3172 peptides using MALDI and ESI-MS, respectively, and 6254 peptides using an ESI-MS TripleTOF 5600 instrument. All conopeptides derived from transcriptomic sequences could be matched to masses obtained on the TripleTOF within 100 ppm accuracy, with 66 (63%) providing MS/MS coverage that unambiguously confirmed these matches. Comprehensive integration of transcriptomic and proteomic data revealed for the first time that the vast majority of the conopeptide diversity arises from a more limited set of genes through a process of variable peptide processing, which generates conopeptides with alternative cleavage sites, heterogeneous post-translational modifications, and highly variable N- and C-terminal truncations. Variable peptide processing is expected to contribute to the evolution of venoms, and explains how a limited set of

  11. Deep Venomics Reveals the Mechanism for Expanded Peptide Diversity in Cone Snail Venom*

    PubMed Central

    Dutertre, Sébastien; Jin, Ai-hua; Kaas, Quentin; Jones, Alun; Alewood, Paul F.; Lewis, Richard J.

    2013-01-01

    Cone snails produce highly complex venom comprising mostly small biologically active peptides known as conotoxins or conopeptides. Early estimates that suggested 50–200 venom peptides are produced per species have been recently increased at least 10-fold using advanced mass spectrometry. To uncover the mechanism(s) responsible for generating this impressive diversity, we used an integrated approach combining second-generation transcriptome sequencing with high sensitivity proteomics. From the venom gland transcriptome of Conus marmoreus, a total of 105 conopeptide precursor sequences from 13 gene superfamilies were identified. Over 60% of these precursors belonged to the three gene superfamilies O1, T, and M, consistent with their high levels of expression, which suggests these conotoxins play an important role in prey capture and/or defense. Seven gene superfamilies not previously identified in C. marmoreus, including five novel superfamilies, were also discovered. To confirm the expression of toxins identified at the transcript level, the injected venom of C. marmoreus was comprehensively analyzed by mass spectrometry, revealing 2710 and 3172 peptides using MALDI and ESI-MS, respectively, and 6254 peptides using an ESI-MS TripleTOF 5600 instrument. All conopeptides derived from transcriptomic sequences could be matched to masses obtained on the TripleTOF within 100 ppm accuracy, with 66 (63%) providing MS/MS coverage that unambiguously confirmed these matches. Comprehensive integration of transcriptomic and proteomic data revealed for the first time that the vast majority of the conopeptide diversity arises from a more limited set of genes through a process of variable peptide processing, which generates conopeptides with alternative cleavage sites, heterogeneous post-translational modifications, and highly variable N- and C-terminal truncations. Variable peptide processing is expected to contribute to the evolution of venoms, and explains how a limited set of

  12. Mass Fingerprinting of the Venom and Transcriptome of Venom Gland of Scorpion Centruroides tecomanus

    PubMed Central

    Valdez-Velázquez, Laura L.; Quintero-Hernández, Verónica; Romero-Gutiérrez, Maria Teresa; Coronas, Fredy I. V.; Possani, Lourival D.

    2013-01-01

    Centruroides tecomanus is a Mexican scorpion endemic of the State of Colima, that causes human fatalities. This communication describes a proteome analysis obtained from milked venom and a transcriptome analysis from a cDNA library constructed from two pairs of venom glands of this scorpion. High perfomance liquid chromatography separation of soluble venom produced 80 fractions, from which at least 104 individual components were identified by mass spectrometry analysis, showing to contain molecular masses from 259 to 44,392 Da. Most of these components are within the expected molecular masses for Na+- and K+-channel specific toxic peptides, supporting the clinical findings of intoxication, when humans are stung by this scorpion. From the cDNA library 162 clones were randomly chosen, from which 130 sequences of good quality were identified and were clustered in 28 contigs containing, each, two or more expressed sequence tags (EST) and 49 singlets with only one EST. Deduced amino acid sequence analysis from 53% of the total ESTs showed that 81% (24 sequences) are similar to known toxic peptides that affect Na+-channel activity, and 19% (7 unique sequences) are similar to K+-channel especific toxins. Out of the 31 sequences, at least 8 peptides were confirmed by direct Edman degradation, using components isolated directly from the venom. The remaining 19%, 4%, 4%, 15% and 5% of the ESTs correspond respectively to proteins involved in cellular processes, antimicrobial peptides, venom components, proteins without defined function and sequences without similarity in databases. Among the cloned genes are those similar to metalloproteinases. PMID:23840487

  13. Chironex fleckeri (Box Jellyfish) Venom Proteins

    PubMed Central

    Brinkman, Diane L.; Konstantakopoulos, Nicki; McInerney, Bernie V.; Mulvenna, Jason; Seymour, Jamie E.; Isbister, Geoffrey K.; Hodgson, Wayne C.

    2014-01-01

    The box jellyfish Chironex fleckeri produces extremely potent and rapid-acting venom that is harmful to humans and lethal to prey. Here, we describe the characterization of two C. fleckeri venom proteins, CfTX-A (∼40 kDa) and CfTX-B (∼42 kDa), which were isolated from C. fleckeri venom using size exclusion chromatography and cation exchange chromatography. Full-length cDNA sequences encoding CfTX-A and -B and a third putative toxin, CfTX-Bt, were subsequently retrieved from a C. fleckeri tentacle cDNA library. Bioinformatic analyses revealed that the new toxins belong to a small family of potent cnidarian pore-forming toxins that includes two other C. fleckeri toxins, CfTX-1 and CfTX-2. Phylogenetic inferences from amino acid sequences of the toxin family grouped CfTX-A, -B, and -Bt in a separate clade from CfTX-1 and -2, suggesting that the C. fleckeri toxins have diversified structurally and functionally during evolution. Comparative bioactivity assays revealed that CfTX-1/2 (25 μg kg−1) caused profound effects on the cardiovascular system of anesthetized rats, whereas CfTX-A/B elicited only minor effects at the same dose. Conversely, the hemolytic activity of CfTX-A/B (HU50 = 5 ng ml−1) was at least 30 times greater than that of CfTX-1/2. Structural homology between the cubozoan toxins and insecticidal three-domain Cry toxins (δ-endotoxins) suggests that the toxins have a similar pore-forming mechanism of action involving α-helices of the N-terminal domain, whereas structural diversification among toxin members may modulate target specificity. Expansion of the cnidarian toxin family therefore provides new insights into the evolutionary diversification of box jellyfish toxins from a structural and functional perspective. PMID:24403082

  14. Venomics, lethality and neutralization of Naja kaouthia (monocled cobra) venoms from three different geographical regions of Southeast Asia.

    PubMed

    Tan, Kae Yi; Tan, Choo Hock; Fung, Shin Yee; Tan, Nget Hong

    2015-04-29

    Previous studies showed that venoms of the monocled cobra, Naja kaouthia from Thailand and Malaysia are substantially different in their median lethal doses. The intraspecific venom variations of N. kaouthia, however, have not been fully elucidated. Here we investigated the venom proteomes of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V) through reverse-phase HPLC, SDS-PAGE and tandem mass spectrometry. The venom proteins comprise 13 toxin families, with three-finger toxins being the most abundant (63-77%) and the most varied (11-18 isoforms) among the three populations. NK-T has the highest content of neurotoxins (50%, predominantly long neurotoxins), followed by NK-V (29%, predominantly weak neurotoxins and some short neurotoxins), while NK-M has the least (18%, some weak neurotoxins but less short and long neurotoxins). On the other hand, cytotoxins constitute the main bulk of toxins in NK-M and NK-V venoms (up to 45% each), but less in NK-T venom (27%). The three venoms show different lethal potencies that generally reflect the proteomic findings. Despite the proteomic variations, the use of Thai monovalent and Neuro polyvalent antivenoms for N. kaouthia envenomation in the three regions is appropriate as the different venoms were neutralized by the antivenoms albeit at different degrees of effectiveness. Biogeographical variations were observed in the venom proteome of monocled cobra (Naja kaouthia) from Malaysia, Thailand and Vietnam. The Thai N. kaouthia venom is particularly rich in long neurotoxins, while the Malaysian and Vietnamese specimens were predominated with cytotoxins. The differentially expressed toxin profile accounts for the discrepancy in the lethal dose of the venom from different populations. Commercially available Thai antivenoms (monovalent and polyvalent) were able to neutralize the three venoms at different effective doses, hence supporting their uses in the three regions. While dose adjustment according to

  15. Exploring the venom proteome of the western diamondback rattlesnake, Crotalus atrox, via snake venomics and combinatorial peptide ligand library approaches.

    PubMed

    Calvete, Juan J; Fasoli, Elisa; Sanz, Libia; Boschetti, Egisto; Righetti, Pier Giorgio

    2009-06-01

    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

  16. [Drug or plant substances which antagonize venoms or potentiate antivenins].

    PubMed

    Chippaux, J P; Rakotonirina, V S; Rakotonirina, A; Dzikouk, G

    1997-01-01

    Dendroaspis jamesoni (Elapidae) and Echis oceliatus (Viperidae) are responsible for most of severe evenomation in Cameroon. Toxicity of venoms of these two species has been measured using mice according to the method of Spearman & Kàrber. The effect on experimental envenomation of various drugs (atropine, promethazine, neostigmine, hydrocortisone, pentosane sulfuric polyester, heparin, tranexamic acid and aminocaproic acid) and plant extracts (Schumanniophyton magnificum, Bidens pilosa, Securidaca longepedunculata and Garcinia lucida) has been observed associated or not with the antivenom lpser Afrique (SAV). The venom of D. jamesoni contains neurotoxins agonizing and antagonising acetylcholine. The toxicity of the venom did not depend on the route of injection. Atropine, promethazine, neostigmine and hydrocortisone protected animals against a venom dose up to 2 LD50. Moreover, atropine and promethazine potentiated the SAV. Similar results have been obtained with extracts from S. magnificum and B. pilosa. The venom of E. ocellatus induces haemorrhage and necrosis. The toxicity increased by 3-fold when the venom was injected through intravenous or intraperitoneal route, compared to intramuscular route. Pentosane sulfuric polyester and tranexamic acid protected mice against doses up to 3 LD50. Pentosane sulfuric polyester, hydrocortisone, heparin and aminocaproic acid increased the SAV protective titre by 50%. However, tried plant extracts weakly antagonised the venom and did not potentiate the SAV.

  17. Micrurus snake venoms activate human complement system and generate anaphylatoxins

    PubMed Central

    2012-01-01

    Background The genus Micrurus, coral snakes (Serpentes, Elapidae), comprises more than 120 species and subspecies distributed from the south United States to the south of South America. Micrurus snake bites can cause death by muscle paralysis and further respiratory arrest within a few hours after envenomation. Clinical observations show mainly neurotoxic symptoms, although other biological activities have also been experimentally observed, including cardiotoxicity, hemolysis, edema and myotoxicity. Results In the present study we have investigated the action of venoms from seven species of snakes from the genus Micrurus on the complement system in in vitro studies. Several of the Micrurus species could consume the classical and/or the lectin pathways, but not the alternative pathway, and C3a, C4a and C5a were generated in sera treated with the venoms as result of this complement activation. Micrurus venoms were also able to directly cleave the α chain of the component C3, but not of the C4, which was inhibited by 1,10 Phenanthroline, suggesting the presence of a C3α chain specific metalloprotease in Micrurus spp venoms. Furthermore, complement activation was in part associated with the cleavage of C1-Inhibitor by protease(s) present in the venoms, which disrupts complement activation control. Conclusion Micrurus venoms can activate the complement system, generating a significant amount of anaphylatoxins, which may assist due to their vasodilatory effects, to enhance the spreading of other venom components during the envenomation process. PMID:22248157

  18. Scyphozoan jellyfish venom metalloproteinases and their role in the cytotoxicity.

    PubMed

    Lee, Hyunkyoung; Jung, Eun-sun; Kang, Changkeun; Yoon, Won Duk; Kim, Jong-Shu; Kim, Euikyung

    2011-09-01

    The present study, for the first time, comparatively investigated the enzymatic activities (proteases and hyaluronidases) in the venoms of four Scyphozoan jellyfish species, including Nemopilema nomurai, Rhopilema esculenta, Cyanea nozakii, and Aurelia aurita. For this, various zymographic analyses were performed using assay specific substrates. Interestingly, all the four jellyfish venoms showed gelatinolytic, caseinolytic, and fibrinolytic activities, each of which contains a multitude of enzyme components with molecular weights between 17 and 130 kDa. These four jellyfish venoms demonstrated a huge variation in their proteolytic activities in quantitative and qualitative manner depending on the species. Most of these enzymatic activities were disappeared by the treatment of 1,10-phenanthroline, suggesting they might be belonged to metalloproteinases. Toxicological significance of these venom proteases was examined by comparing their proteolytic activity and the cytotoxicity in NIH 3T3 cells. The relative cytotoxic potency was C. nozakii > N. nomurai > A. aurita > R. esculenta. The cytotoxicity of jellyfish venom shows a positive correlation with its overall proteolytic activity. The metalloproteinases appear to play an important role in the induction of jellyfish venom toxicities. In conclusion, the present report proposes a novel finding of Scyphozoan jellyfish venom metalloproteinases and their potential role in the cytotoxicity.

  19. Effects of snake venom polypeptides on central nervous system.

    PubMed

    Osipov, Alexey; Utkin, Yuri

    2012-12-01

    The nervous system is a primary target for animal venoms as the impairment of its function results in the fast and efficient immobilization or death of a prey. There are numerous evidences about effects of crude snake venoms or isolated toxins on peripheral nervous system. However, the data on their interactions with the central nervous system (CNS) are not abundant, as the blood-brain barrier (BBB) impedes penetration of these compounds into brain. This updated review presents the data about interaction of snake venom polypeptides with CNS. Such data will be described according to three main modes of interactions: - Direct in vivo interaction of CNS with venom polypeptides either capable to penetrate BBB or injected into the brain. - In vitro interactions of cell or sub-cellular fractions of CNS with crude venoms or purified toxins. - Indirect effects of snake venoms or their components on functioning of CNS under different conditions. Although the venom components penetrating BBB are not numerous, they seem to be the most suitable candidates for the leads in drug design. The compounds with other modes of action are more abundant and better studied, but the lack of the data about their ability to penetrate BBB may substantially aggravate the potentials for their medical perspectives. Nevertheless, many such compounds are used for research of CNS in vitro. These investigations may give invaluable information for understanding the molecular basis of CNS diseases and thus lay the basis for targeted drug design. This aspect also will be outlined in the review.

  20. Effects of Animal Venoms and Toxins on Hallmarks of Cancer.

    PubMed

    Chaisakul, Janeyuth; Hodgson, Wayne C; Kuruppu, Sanjaya; Prasongsook, Naiyarat

    2016-01-01

    Animal venoms are a cocktail of proteins and peptides, targeting vital physiological processes. Venoms have evolved to assist in the capture and digestion of prey. Key venom components often include neurotoxins, myotoxins, cardiotoxins, hematoxins and catalytic enzymes. The pharmacological activities of venom components have been investigated as a source of potential therapeutic agents. Interestingly, a number of animal toxins display profound anticancer effects. These include toxins purified from snake, bee and scorpion venoms effecting cancer cell proliferation, migration, invasion, apoptotic activity and neovascularization. Indeed, the mechanism behind the anticancer effect of certain toxins is similar to that of agents currently used in chemotherapy. For example, Lebein is a snake venom disintegrin which generates anti-angiogenic effects by inhibiting vascular endothelial growth factors (VEGF). In this review article, we highlight the biological activities of animal toxins on the multiple steps of tumour formation or hallmarks of cancer. We also discuss recent progress in the discovery of lead compounds for anticancer drug development from venom components.

  1. Ancient Venom Systems: A Review on Cnidaria Toxins.

    PubMed

    Jouiaei, Mahdokht; Yanagihara, Angel A; Madio, Bruno; Nevalainen, Timo J; Alewood, Paul F; Fry, Bryan G

    2015-06-18

    Cnidarians are the oldest extant lineage of venomous animals. Despite their simple anatomy, they are capable of subduing or repelling prey and predator species that are far more complex and recently evolved. Utilizing specialized penetrating nematocysts, cnidarians inject the nematocyst content or "venom" that initiates toxic and immunological reactions in the envenomated organism. These venoms contain enzymes, potent pore forming toxins, and neurotoxins. Enzymes include lipolytic and proteolytic proteins that catabolize prey tissues. Cnidarian pore forming toxins self-assemble to form robust membrane pores that can cause cell death via osmotic lysis. Neurotoxins exhibit rapid ion channel specific activities. In addition, certain cnidarian venoms contain or induce the release of host vasodilatory biogenic amines such as serotonin, histamine, bunodosine and caissarone accelerating the pathogenic effects of other venom enzymes and porins. The cnidarian attacking/defending mechanism is fast and efficient, and massive envenomation of humans may result in death, in some cases within a few minutes to an hour after sting. The complexity of venom components represents a unique therapeutic challenge and probably reflects the ancient evolutionary history of the cnidarian venom system. Thus, they are invaluable as a therapeutic target for sting treatment or as lead compounds for drug design.

  2. Effects of Animal Venoms and Toxins on Hallmarks of Cancer

    PubMed Central

    Chaisakul, Janeyuth; Hodgson, Wayne C.; Kuruppu, Sanjaya; Prasongsook, Naiyarat

    2016-01-01

    Animal venoms are a cocktail of proteins and peptides, targeting vital physiological processes. Venoms have evolved to assist in the capture and digestion of prey. Key venom components often include neurotoxins, myotoxins, cardiotoxins, hematoxins and catalytic enzymes. The pharmacological activities of venom components have been investigated as a source of potential therapeutic agents. Interestingly, a number of animal toxins display profound anticancer effects. These include toxins purified from snake, bee and scorpion venoms effecting cancer cell proliferation, migration, invasion, apoptotic activity and neovascularization. Indeed, the mechanism behind the anticancer effect of certain toxins is similar to that of agents currently used in chemotherapy. For example, Lebein is a snake venom disintegrin which generates anti-angiogenic effects by inhibiting vascular endothelial growth factors (VEGF). In this review article, we highlight the biological activities of animal toxins on the multiple steps of tumour formation or hallmarks of cancer. We also discuss recent progress in the discovery of lead compounds for anticancer drug development from venom components. PMID:27471574

  3. Role of the inflammasome in defense against venoms

    PubMed Central

    Palm, Noah W.; Medzhitov, Ruslan

    2013-01-01

    Venoms consist of a complex mixture of toxic components that are used by a variety of animal species for defense and predation. Envenomation of mammalian species leads to an acute inflammatory response and can lead to the development of IgE-dependent venom allergy. However, the mechanisms by which the innate immune system detects envenomation and initiates inflammatory and allergic responses to venoms remain largely unknown. Here we show that bee venom is detected by the NOD-like receptor family, pyrin domain-containing 3 inflammasome and can trigger activation of caspase-1 and the subsequent processing and unconventional secretion of the leaderless proinflammatory cytokine IL-1β in macrophages. Whereas activation of the inflammasome by bee venom induces a caspase-1–dependent inflammatory response, characterized by recruitment of neutrophils to the site or envenomation, the inflammasome is dispensable for the allergic response to bee venom. Finally, we find that caspase-1–deficient mice are more susceptible to the noxious effects of bee and snake venoms, suggesting that a caspase-1–dependent immune response can protect against the damaging effects of envenomation. PMID:23297192

  4. Alkaline Phosphatase from Venom of the Endoparasitoid Wasp, Pteromalus puparum

    PubMed Central

    Zhu, Jia-Ying; Yin Ye, Gong; Fang, Qi; Hu, Cui

    2010-01-01

    Using chromogenic substrates 5-bromo-4-chloro-3′-indolyl phosphate and nitro blue tetrazolium, alkaline phosphatase (ALPase) was histochemically detected in the venom apparatus of an endoparasitoid wasp, Pteromalus puparum L. (Hymenoptera: Pteromalidae). Ultrastructural observations demonstrated its presence in the secretory vesicles and nuclei of the venom gland secretory cells. Using p-nitrophenyl phosphate as substrate to measure enzyme activity, the venom ALPase was found to be temperature dependent with bivalent cation effects. The full-length cDNA sequence of ALPase was amplified from the cDNA library of the venom apparatus of P. puparum, providing the first molecular characterization of ALPase in the venom of a parasitoid wasp. The cDNA consisted of 2645 bp with a 1623 bp open reading frame coding for 541 deduced amino acids with a predicted molecular mass of 59.83 kDa and pI of 6.98. Using multiple sequence alignment, the deduced amino acid sequence shared high identity to its counterparts from other insects. A signal peptide and a long conserved ALPase gene family signature sequence were observed. The amino acid sequence of this venom protein was characterized with different potential glycosylation, myristoylation, phosphorylation sites and metal ligand sites. The transcript of the ALPase gene was detected by RT-PCR in the venom apparatus with development related expression after adult wasp emergence, suggesting a possible correlation with the oviposition process. PMID:20575745

  5. Autonomic neurotoxicity of jellyfish and marine animal venoms.

    PubMed

    Burnett, J W; Weinrich, D; Williamson, J A; Fenner, P J; Lutz, L L; Bloom, D A

    1998-04-01

    Venoms and poisons of jellyfish and other marine animals can induce damage to the human nervous and circulatory systems. Clues to the pathogenesis and clinical manifestations of these lesions can be obtained from data of human envenomations and animal experimentation. Because many investigators are unaware that marine animal venoms have autonomic actions, this paper aims to elucidate the broad antagonistic or toxic effects these compounds have on the autonomic nervous system. Marine venoms can affect ion transport of particularly sodium and calcium, induce channels or pores in neural and muscular cellular membranes, alter intracellular membranes of organelles and release mediators of inflammation. The box jellyfish, particularly Chironex fleckeri, in the Indo-Pacific region, is the world's most venomous marine animal and is responsible for autonomic disorders in patients. The symptoms induced by these venoms are vasospasm, cardiac irregularities, peripheral neuropathy, aphonia, ophthalmic abnormalities and parasympathetic dysautonomia. Cases of Irukandji syndrome, caused by the jellyfish Carukia barnesi, have symptoms that mimic excessive catecholamine release. Coelenterate venoms can also target the myocardium, Purkinje fiber, A-V node or aortic ring. Actions on nerves, as well as skeletal, smooth or cardiac muscle occur. Recent studies indicate that the hepatic P-450 enzyme family may be injured by these compounds. The multiplicity of these venom activities means that a thorough understanding of the sting pathogenesis will be essential in devising effective therapies.

  6. [Plasminogen activator from Agkistrodon halys halys venom].

    PubMed

    Karbovs'kyĭ, V L; Levkiv, M Iu; Savchuk, O M; Hornyts'ka, O V; Volkov, H L; Bukhan, Ts

    2006-01-01

    Plasminogen activator "Ahh-32" from Agkistrodon halys halys venom has been isolated and purified using affinity and ion-exchange chromatography. The purified enzyme consists of the single peptide-chain with molecular weigth of 32 kDa. It can convert free plasminogen into active form--plasmin. "Ahh-32" was inhibited by DFP and benzamidine. Besides, the enzyme influences significantly the activation of plasminogen by streptokinase without having effect on analogical process in case of usage of tissue tipe plasminogen activator. The obtained protein can be used as an instrument under investigation of protein-protein interactions in haemostasis system.

  7. Anti-snake venom activities of ethanolic extract of fruits of Piper longum L. (Piperaceae) against Russell's viper venom: characterization of piperine as active principle.

    PubMed

    Shenoy, P A; Nipate, S S; Sonpetkar, J M; Salvi, N C; Waghmare, A B; Chaudhari, P D

    2013-05-20

    Piper longum L. fruits have been traditionally used against snakebites in north-eastern and southern region of India. To examine the ability of ethanolic extract of fruits of Piper longum L., Piperaceae (PLE) and piperine, one of the main active principles of Piper longum, to inhibit the Russell's viper (Doboia russelii, Viperidae) snake venom activities. Anti-snake venom activities of ethanolic extract of fruits of Piper longum L. (Piperaceae) and piperine against Russell's viper venom was studied in embryonated fertile chicken eggs, mice and rats by using various models as follows: inhibition of venom lethal action, inhibition of venom haemorrhagic action (in vitro), inhibition of venom haemorrhagic action (in vivo), inhibition of venom necrotizing action, inhibition of venom defibrinogenating action, inhibition of venom induced paw edema, inhibition of venom induced mast cell degranulation, creatine kinase assay and assay for catalase activity. PLE was found to inhibit the venom induced haemorrhage in embryonated fertile chicken eggs. Administration of PLE and piperine significantly (p<0.01) inhibited venom induced lethality, haemorrhage, necrosis, defibrinogenation and inflammatory paw edema in mice in a dose dependent manner. PLE and piperine also significantly (p<0.01) reduced venom induced mast cell degranulation in rats. Venom induced decrease in catalase enzyme levels in mice kidney tissue and increase in creatine kinase enzyme levels in mice serum were significantly (p<0.01) reversed by administration of both PLE and piperine. PLE possesses good anti-snake venom properties and piperine is one of the compounds responsible for the effective venom neutralizing ability of the plant. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Neutralization of Apis mellifera bee venom activities by suramin.

    PubMed

    El-Kik, Camila Z; Fernandes, Fabrício F A; Tomaz, Marcelo Amorim; Gaban, Glauco A; Fonseca, Tatiane F; Calil-Elias, Sabrina; Oliveira, Suellen D S; Silva, Claudia L M; Martinez, Ana Maria Blanco; Melo, Paulo A

    2013-06-01

    In this work we evaluated the ability of suramin, a polysulfonated naphthylurea derivative, to antagonize the cytotoxic and enzymatic effects of the crude venom of Apis mellifera. Suramin was efficient to decrease the lethality in a dose-dependent way. The hemoconcentration caused by lethal dose injection of bee venom was abolished by suramin (30 μg/g). The edematogenic activity of the venom (0.3 μg/g) was antagonized by suramin (10 μg/g) in all treatment protocols. The changes in the vascular permeability caused by A. mellifera (1 μg/g) venom were inhibited by suramin (30 μg/g) in the pre- and posttreatment as well as when the venom was preincubated with suramin. In addition, suramin also inhibited cultured endothelial cell lesion, as well as in vitro myotoxicity, evaluated in mouse extensor digitorum longus muscle, which was inhibited by suramin (10 and 25 μM), decreasing the rate of CK release, showing that suramin protected the sarcolemma against damage induced by components of bee venom (2.5 μg/mL). Moreover, suramin inhibited the in vivo myotoxicity induced by i.m. injection of A. mellifera venom in mice (0.5 μg/g). The analysis of the area under the plasma CK vs. time curve showed that preincubation, pre- and posttreatment with suramin (30 μg/g) inhibited bee venom myotoxic activity in mice by about 89%, 45% and 40%, respectively. Suramin markedly inhibited the PLA2 activity in a concentration-dependent way (1-30 μM). Being suramin a polyanion molecule, the effects observed may be due to the interaction of its charges with the polycation components present in A. mellifera bee venom. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. EAACI Guidelines on Allergen Immunotherapy: Hymenoptera venom allergy.

    PubMed

    Sturm, Gunter J; Varga, Eva-Maria; Roberts, Graham; Mosbech, Holger; Bilò, M Beatrice; Akdis, Cezmi A; Antolín-Amérigo, Darío; Cichocka-Jarosz, Ewa; Gawlik, Radoslaw; Jakob, Thilo; Kosnik, Mitja; Lange, Joanna; Mingomataj, Ervin; Mitsias, Dimitris I; Ollert, Markus; Oude Elberink, Joanna N G; Pfaar, Oliver; Pitsios, Constantinos; Pravettoni, Valerio; Ruëff, Franziska; Sin, Betül Ayşe; Agache, Ioana; Angier, Elizabeth; Arasi, Stefania; Calderón, Moises A; Fernandez-Rivas, Montserrat; Halken, Susanne; Jutel, Marek; Lau, Susanne; Pajno, Giovanni B; van Ree, Ronald; Ryan, Dermot; Spranger, Otto; van Wijk, Roy Gerth; Dhami, Sangeeta; Zaman, Hadar; Sheikh, Aziz; Muraro, Antonella

    2017-07-27

    Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid or ant sting. Systemic allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate-to-severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1 -antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom allergic children and adults to prevent further moderate to severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline auto-injector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Enzymatic analysis of venom from Cuban scorpion Rhopalurus junceus

    PubMed Central

    Díaz-García, Alexis; Ruiz-Fuentes, Jenny Laura; Yglesias-Rivera, Arianna; Rodríguez-Sánchez, Hermis; Riquenes Garlobo, Yanelis; Fleitas Martinez, Osmel; Fraga Castro, José A

    2015-01-01

    Rhopalurus junceus scorpion venom has been identified as a natural extract with anticancer potential. Interestingly, this scorpion venom does not cause adverse symptoms in humans. However, there is scarce information about its composition and enzymatic activity. In this work, we determined the electrophoretic profile of the venom, the gelatinase and caseinolytic activity, and the phospholipase A2 (PLA2) and hemolytic activity. The effect of different venom doses (6.25, 12.5 and 25 mg/kg) on gastrocnemius muscle was also measured as CK and LDH activity in serum. The presence of hyaluronidase was determined by turbidimetric assay. The effect of different fractions obtained by gel filtration chromatography were evaluated at different concentrations (0.05, 0.1, 0.2, 0.4, 0.6mg/ml) against lung cancer cell A549 and lung normal cell MRC-5 using MTT assay. The electrophoretic profile demonstrated the presence of proteins bands around 67kDa, 43kDa, 18.4kDa and a majority band below 14.3kDa. The venom did not showed caseinolytic, gelatinase, PLA2 and hemolytic activity even at highest venom concentration used in the study. Scorpion venom only showed a significant toxic effect on gastrocnemius muscles identified by CK and LDH release after subcutaneous injection of 12.5 and 25mg/kg. Low molecular weight fractions (<4kDa) induced a significant cytotoxicity in A549 cells while high molecular weight proteins (45–60kDa) were responsible for hyaluronidase activity and toxic effect against MRC-5. Experiments indicate that Rhopalurus junceus scorpion venom has low enzymatic activity, which could contribute to the low toxic potential of this scorpion venom. PMID:26605039

  11. Effect of brown spider venom on basement membrane structures.

    PubMed

    Veiga, S S; Feitosa, L; dos Santos, V L; de Souza, G A; Ribeiro, A S; Mangili, O C; Porcionatto, M A; Nader, H B; Dietrich, C P; Brentani, R R; Gremski, W

    2000-07-01

    Loxoscelism or necrotic arachnidism are terms used to describe lesions and reactions induced by bites (envenomation) from spiders of the genus Loxosceles. Envenomation has been reported to provoke dermonecrosis and haemorrhage at the bite site and haemolysis, disseminated intravascular coagulation and renal failure. The purpose of this work was to study the effect of the venom of the brown spider Loxosceles intermedia on basement membrane structures and on its major constituent molecules. Light microscopy observations showed that L. intermedia venom obtained through electric shock, which reproduces two major signals of Loxoscelism in the laboratory, exhibits activity toward basement membrane structures in mouse Engelbreth-Holm-Swarm (EHS) sarcoma. Basement degradation was seen by a reduced periodic acid-Schiff (PAS) and alcian blue staining as well as by a reduced immunostaining for laminin when compared to control experiments. Electron microscopy studies confirmed the above results, showing the action of the venom on EHS-basement membranes and demonstrating that these tissue structures are susceptible to the venom. Using purified components of the basement membrane, we determined through SDS-PAGE and agarose gel that the venom is not active toward laminin or type IV collagen, but is capable of cleaving entactin and endothelial heparan sulphate proteoglycan. In addition, when EHS tissue was incubated with venom we detected a release of laminin into the supernatant, corroborating the occurrence of some basement membrane disruption. The venom-degrading effect on entactin was blocked by 1, 10-phenanthroline, but not by other protease inhibitors such as PMSF, NEM or pepstatin-A. By using light microscopy associated with PAS staining we were able to identify that 1,10-phenanthroline also inhibits EHS-basement membrane disruption evoked by venom, corroborating that a metalloprotease of venom is involved in these effects. Degradation of these extracellular matrix

  12. Immobilizing and lethal effects of spider venoms on the cockroach and the common mealbeetle.

    PubMed

    Friedel, T; Nentwig, W

    1989-01-01

    Immobilizing and lethal effects of the venoms obtained from six spider species (Brachypelma albopilosum, Atrax robustus, Cupiennius salei, Selenops mexicanus, Tegenaria atrica, Argiope bruennichi) were tested on Blatta orientalis (cockroach) and Tenebrio molitor (common mealbeetle). The immobilizing effects were quantified by measuring insect locomotor activity in circle arenas observed over 72 hr after venom injection. Both insect species showed cramps, quivering and jerking of the limbs as well as flaccid paralysis after venom injection. Through relative toxicity of the venoms tested is the same in T. molitor and B. orientalis, T. molitor is absolutely less sensitive to spider venoms. The effects on locomotor activity show time characteristics specific for each venom. A dependence of the venom paralyzing effects on insect locomotor activity, low intensity of the initial excitatory phase of the venom effects and partial recovery of the insects was found with A. bruennichi and T. atrica venom. The maximal venom yields of A. bruennichi and S. mexicanus are not lethal to B. orientalis, indicating that the mere immobilizing effects of spider venoms are far more crucial to prey capture than their lethal effects. The contribution of a variety of differently acting neurotoxic components in spider venoms to the observed venom effects on insects and the significance of the venoms in spider nutrition, hunting behaviour and ecology are discussed.

  13. Production and packaging of a biological arsenal: Evolution of centipede venoms under morphological constraint

    PubMed Central

    Undheim, Eivind A. B.; Hamilton, Brett R.; Kurniawan, Nyoman D.; Bowlay, Greg; Cribb, Bronwen W.; Merritt, David J.; Fry, Bryan G.; King, Glenn F.; Venter, Deon J.

    2015-01-01

    Venom represents one of the most extreme manifestations of a chemical arms race. Venoms are complex biochemical arsenals, often containing hundreds to thousands of unique protein toxins. Despite their utility for prey capture, venoms are energetically expensive commodities, and consequently it is hypothesized that venom complexity is inversely related to the capacity of a venomous animal to physically subdue prey. Centipedes, one of the oldest yet least-studied venomous lineages, appear to defy this rule. Although scutigeromorph centipedes produce less complex venom than those secreted by scolopendrid centipedes, they appear to rely heavily on venom for prey capture. We show that the venom glands are large and well developed in both scutigerid and scolopendrid species, but that scutigerid forcipules lack the adaptations that allow scolopendrids to inflict physical damage on prey and predators. Moreover, we reveal that scolopendrid venom glands have evolved to accommodate a much larger number of secretory cells and, by using imaging mass spectrometry, we demonstrate that toxin production is heterogeneous across these secretory units. We propose that the differences in venom complexity between centipede orders are largely a result of morphological restrictions of the venom gland, and consequently there is a strong correlation between the morphological and biochemical complexity of this unique venom system. The current data add to the growing body of evidence that toxins are not expressed in a spatially homogenous manner within venom glands, and they suggest that the link between ecology and toxin evolution is more complex than previously thought. PMID:25775536

  14. Production and packaging of a biological arsenal: evolution of centipede venoms under morphological constraint.

    PubMed

    Undheim, Eivind A B; Hamilton, Brett R; Kurniawan, Nyoman D; Bowlay, Greg; Cribb, Bronwen W; Merritt, David J; Fry, Bryan G; King, Glenn F; Venter, Deon J

    2015-03-31

    Venom represents one of the most extreme manifestations of a chemical arms race. Venoms are complex biochemical arsenals, often containing hundreds to thousands of unique protein toxins. Despite their utility for prey capture, venoms are energetically expensive commodities, and consequently it is hypothesized that venom complexity is inversely related to the capacity of a venomous animal to physically subdue prey. Centipedes, one of the oldest yet least-studied venomous lineages, appear to defy this rule. Although scutigeromorph centipedes produce less complex venom than those secreted by scolopendrid centipedes, they appear to rely heavily on venom for prey capture. We show that the venom glands are large and well developed in both scutigerid and scolopendrid species, but that scutigerid forcipules lack the adaptations that allow scolopendrids to inflict physical damage on prey and predators. Moreover, we reveal that scolopendrid venom glands have evolved to accommodate a much larger number of secretory cells and, by using imaging mass spectrometry, we demonstrate that toxin production is heterogeneous across these secretory units. We propose that the differences in venom complexity between centipede orders are largely a result of morphological restrictions of the venom gland, and consequently there is a strong correlation between the morphological and biochemical complexity of this unique venom system. The current data add to the growing body of evidence that toxins are not expressed in a spatially homogenous manner within venom glands, and they suggest that the link between ecology and toxin evolution is more complex than previously thought.

  15. Quantity, analysis, and lethality of European and Africanized honey bee venoms.

    PubMed

    Schumacher, M J; Schmidt, J O; Egen, N B; Lowry, J E

    1990-07-01

    Venom from Africanized honey bees (derived mainly from Apis mellifera scutellata) was compared with venom from domestic, European bees by study of lethality, immunological cross-reactivity, venom yield, isoelectric focusing (IEF) patterns, and melittin titers. The LD50s of European and Africanized bee venom by iv injection in mice were similar. In venom neutralization experiments, Africanized bee venom was mixed with antibodies from a beekeeper exposed only to European bees and used to challenge mice. Survival times of mice given these mixtures were significantly prolonged, indicating that human serum antibodies to European bee venom neutralized the lethal effects of Africanized bee venom. Reservoirs from Africanized bees contained less venom than European bees (94 and 147 micrograms venom/bee, respectively) and Africanized bee venom had a lower melittin content. The IEF patterns of venom from individual European bees varied considerably, as did IEF patterns of individual Africanized bees. Pools of venom from 1,000 bees of each population of A. mellifera showed noticeable but less obvious electrophoretic differences. The findings suggest that multiple stinging, and not increased venom potency or delivery, is the cause of serious reactions from Africanized bee attacks.

  16. Label-Free (XIC) Quantification of Venom Procoagulant and Neurotoxin Expression in Related Australian Elapid Snakes Gives Insight into Venom Toxicity Evolution.

    PubMed

    Skejic, Jure; Steer, David L; Dunstan, Nathan; Hodgson, Wayne C

    2015-11-06

    This study demonstrates a direct role of venom protein expression alteration in the evolution of snake venom toxicity. Avian skeletal muscle contractile response to exogenously administered acetylcholine is completely inhibited upon exposure to South Australian and largely preserved following exposure to Queensland eastern brown snake Pseudonaja textilis venom, indicating potent postsynaptic neurotoxicity of the former and lack thereof of the latter venom. Label-free quantitative proteomics reveals extremely large differences in the expression of postsynaptic three-finger α-neurotoxins in these venoms, explaining the difference in the muscle contractile response and suggesting that the type of toxicity induced by venom can be modified by altered expression of venom proteins. Furthermore, the onset of neuromuscular paralysis in the rat phrenic nerve-diaphragm preparation occurs sooner upon exposure to the venom (10 μg/mL) with high expression of α-neurotoxins than the venoms containing predominately presynaptic β-neurotoxins. The study also finds that the onset of rat plasma coagulation is faster following exposure to the venoms with higher expression of venom prothrombin activator subunits. This is the first quantitative proteomic study that uses extracted ion chromatogram peak areas (MS1 XIC) of distinct homologous tryptic peptides to directly show the differences in the expression of venom proteins.

  17. Preliminary Fractionation of Tiger Rattlesnake (Crotalus tigris) Venom

    DTIC Science & Technology

    1990-01-31

    any gross tissue pathology examined and noted. The LD5 0 was cal LulJud by the Spearman - Karber method (WORLD I EALTH ORGANIZATION, 1981). Venom samples...Veterans I lospital, Venom Research Laboratory, Salt I ,ku City, IJI). Mojave toxin was purified from .QL1culuj1a s . cuu ilJ venom by the method of...minfi Protein 11 unit according to the method of LAEMMI, 1(1970). Apparent nioluctilar weights were determined by Andrews plots. Protuins wtere delected

  18. [Snake venom metalloproteinases: structure, biosynthesis and function(s)].

    PubMed

    Limam, I; El Ayeb, M; Marrakchi, N

    2010-01-01

    The biochemical and the pharmacological characterization of snake venoms revealed an important structural and functional polymorphism of proteins which they contain. Among them, snake venom metalloproteases (SVMPs) constitute approximatively 20 to 60% of the whole venom proteins. During the last decades, a significant progress was performed against structure studies and the biosynthesis of the SVMPs. Indeed, several metalloproteases were isolated and characterized against their structural and pharmacological properties. In this review, we report the most important properties concerning the classification, the structure of the various domains of the SVMPs as well as their biosynthesis and their activities as potential therapeutic agents.

  19. Evolution and diversification of the Toxicofera reptile venom system.

    PubMed

    Fry, Bryan G; Vidal, Nicolas; van der Weerd, Louise; Kochva, Elazar; Renjifo, Camila

    2009-03-06

    The diversification of the reptile venom system has been an area of major research but of great controversy. In this review we examine the historical and modern-day efforts of all aspects of the venom system including dentition, glands and secreted toxins and highlight areas of future research opportunities. We use multidisciplinary techniques, including magnetic resonance imaging of venom glands through to molecular phylogenetic reconstruction of toxin evolutionary history, to illustrate the diversity within this integrated weapons system and map the timing of toxin recruitment events over the toxicoferan organismal evolutionary tree.

  20. Cone snail venomics: from novel biology to novel therapeutics.

    PubMed

    Prashanth, Jutty Rajan; Brust, Andreas; Jin, Ai-Hua; Alewood, Paul F; Dutertre, Sébastien; Lewis, Richard J

    2014-10-01

    Peptide neurotoxins from cone snails called conotoxins are renowned for their therapeutic potential to treat pain and several neurodegenerative diseases. Inefficient assay-guided discovery methods have been replaced by high-throughput bioassays integrated with advanced MS and next-generation sequencing, ushering in the era of 'venomics'. In this review, we focus on the impact of venomics on the understanding of cone snail biology as well as the application of venomics to accelerate the discovery of new conotoxins. We also discuss the continued importance of medicinal chemistry approaches to optimize conotoxins for clinical use, with a descriptive case study of MrIA featured.

  1. Venomics of Bungarus caeruleus (Indian krait): Comparable venom profiles, variable immunoreactivities among specimens from Sri Lanka, India and Pakistan.

    PubMed

    Oh, Angeline Mei Feng; Tan, Choo Hock; Ariaranee, Gnanathasan Christeine; Quraishi, Naeem; Tan, Nget Hong

    2017-07-05

    The Indian krait (Bungarus caeruleus) is one of the "Big Four" venomous snakes widely distributed in South Asia. The present venomic study reveals that its venom (Sri Lankan origin) is predominated by phospholipases A2 (64.5% of total proteins), in which at least 4.6% are presynaptically-acting β-bungarotoxin A-chains. Three-finger toxins (19.0%) are the second most abundant, comprising 15.6% κ-neurotoxins, the potent postsynaptically-acting long neurotoxins. Comparative chromatography showed that venom samples from Sri Lanka, India and Pakistan did not exhibit significant variation. These venoms exhibited high immunoreactivity toward VINS Indian Polyvalent Antivenom (VPAV). The Pakistani krait venom, however, had a relatively lower degree of binding, consistent with its moderate neutralization by VPAV (potency=0.3mg venom neutralized per ml antivenom) while the Sri Lankan and Indian venoms were more effectively neutralized (potency of 0.44 mg/ml and 0.48 mg/ml, respectively). Importantly, VPAV was able to neutralize the Sri Lankan and Indian venoms to a comparable extent, supporting its use in Sri Lanka especially in the current situation where Sri Lanka-specific antivenom is unavailable against this species. The findings also indicate that the Pakistani B. caeruleus venom is immunologically less comparable and should be incorporated in the production of a pan-regional, polyspecific antivenom. The Indian krait or blue krait, Bungarus caeruleus, is a highly venomous snake that contributes to the snakebite envenoming problem in South Asia. This is a less aggressive snake species but its accidental bite can cause rapid and severe neurotoxicity, in which the patient may succumb to paralysis, respiratory failure and death within a short frame of time. The proteomic analysis of its venom (sourced from Sri Lanka) unveils its content that well correlates to its envenoming pathophysiology, driven primarily by the abundant presynaptic and postsynaptic neurotoxins (

  2. Snake venomics of monocled cobra (Naja kaouthia) and investigation of human IgG response against venom toxins.

    PubMed

    Laustsen, Andreas H; Gutiérrez, José María; Lohse, Brian; Rasmussen, Arne R; Fernández, Julián; Milbo, Christina; Lomonte, Bruno

    2015-06-01

    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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Lachesis muta muta venom: immunological differences compared with Bothrops atrox venom and importance of specific antivenom therapy.

    PubMed

    Colombini, M; Fernandes, I; Cardoso, D F; Moura-da-Silva, A M

    2001-05-01

    Lachesis muta muta and Bothrops atrox snakes are responsible for most accidents occurring in the Amazon. The clinical features of the accidents are similar; however, there are still controversies about the efficacy of Bothrops antivenoms for treating L. m. muta accidents. In this work, we evaluated the antigenic cross-reactivity between these venoms using polyclonal and monoclonal antibodies and the efficacy of B. atrox and L. m. muta experimental antivenoms in cross-neutralizing the main toxic activities of each venom. Electrophoretic patterns differed consistently between the species. However, antigenic cross-reactivity was extensive except for a few bands. Several species-specific monoclonal antibodies were obtained by immunization of Balb/c mice with L. m. muta whole venom or B. atrox and L. m. muta specific antigens. The monoclonal antibodies specific to L. m. muta recognized different bands of this venom and the antibodies specific to B. atrox recognized a complex pattern on whole venom by Western blotting. These antibodies are important tools for developing an immunoassay able to discriminate patients bitten by these snakes. The experiments involving cross-neutralization of the main activities of the venoms showed that hemorrhage and blood incoagulability induced by B. atrox venom were similarly neutralized by both B. atrox and L. m. muta antivenoms. However, B. atrox antivenom partially neutralized the hemorrhage and completely failed in neutralizing coagulopathy induced by L. m. muta venom. Therefore, antigenic variation between B. atrox and L. m. muta venoms does occur and the use of specific antivenom is suggested for patients bitten by Lachesis snakes.

  4. Effects of venom immunotherapy on serum level of CCL5/RANTES in patients with Hymenoptera venom allergy.

    PubMed

    Gawlik, Radoslaw; Glück, Joanna; Jawor, Barbara; Rogala, Barbara

    2015-01-01

    Hymenoptera venoms are known to cause life-threatening IgE-mediated anaphylactic reactions in allergic individuals. Venom immunotherapy is a recommended treatment of insect allergy with still the mechanism not being completely understood. We decided to assess the serum CCL5/RANTES level in patients who experienced severe anaphylactic reaction to Hymenoptera venom and to find out changes in the course of immunotherapy. Twenty patients (9 men, 11 women, mean age: 31.91 ± 7.63 years) with history of anaphylactic reaction after insect sting were included into the study. Diagnosis was made according to sIgE and skin tests. All of them were enrolled into rush venom immunotherapy with bee or wasp venom extracts (Pharmalgen, ALK-Abello, Horsholm, Denmark). Serum levels of CCL5/RANTES were measured using a commercially available ELISA kit (R&D Systems, Minneapolis, MN). CCL5/RANTES serum concentration are higher in insect venom allergic patients than in healthy controls (887.5 ± 322.77 versus 387.27 ± 85.11 pg/ml). Serum concentration of CCL5/RANTES in insect venom allergic patient was significantly reduced in the course of allergen immunotherapy already after 6 days of vaccination (887.5 ± 322.77 versus 567.32 ± 92.16 pg/ml). CCL5/RANTES serum doesn't correlate with specific IgE. Chemokine CCL5/RANTES participates in allergic inflammation induced by Hymenoptera venom allergens. Specific immunotherapy reduces chemokine CCL5/RANTES serum level already after initial days of venom immunotherapy.

  5. Recombinant phospholipase A1 (Ves v 1) from yellow jacket venom for improved diagnosis of hymenoptera venom hypersensitivity.

    PubMed

    Seismann, Henning; Blank, Simon; Cifuentes, Liliana; Braren, Ingke; Bredehorst, Reinhard; Grunwald, Thomas; Ollert, Markus; Spillner, Edzard

    2010-04-01

    Hymenoptera venoms are known to cause life-threatening IgE-mediated anaphylactic reactions in allergic individuals. Proper diagnosis of hymenoptera venom allergy using venom extracts is severely affected by molecular cross-reactivities. Although non-glycosylated marker allergens would facilitate the identification of the culprit venom, the major allergen phospholipase A1 (Ves v 1) from yellow jacket venom (YJV) remained unavailable so far. Expression of Ves v 1 as wild type and enzymatically inactivated mutant and Ves v 5 in insect cells yielded soluble proteins that were purified via affinity chromatography. Functionality of the recombinant allergens was assessed by enzymatic and biophysical analyses as well as basophil activation tests. Diagnostic relevance was addressed by ELISA-based analyses of sera of YJV-sensitized patients. Both major allergens Ves v 1 and Ves v 5 could be produced in insect cells in secreted soluble form. The recombinant proteins exhibited their particular biochemical and functional characteristics and were capable for activation of human basophils. Assessment of IgE reactivity of sera of YJV-sensitized and double-sensitized patients emphasised the relevance of Ves v 1 in hymenoptera venom allergy. In contrast to the use of singular molecules the combined use of both molecules enabled a reliable assignment of sensitisation to YJV for more than 90% of double-sensitised patients. The recombinant availability of Ves v 1 from yellow jacket venom will contribute to a more detailed understanding of the molecular and allergological mechanisms of insect venoms and may provide a valuable tool for diagnostic and therapeutic approaches in hymenoptera venom allergy.

  6. Recombinant phospholipase A1 (Ves v 1) from yellow jacket venom for improved diagnosis of hymenoptera venom hypersensitivity

    PubMed Central

    2010-01-01

    Background Hymenoptera venoms are known to cause life-threatening IgE-mediated anaphylactic reactions in allergic individuals. Proper diagnosis of hymenoptera venom allergy using venom extracts is severely affected by molecular cross-reactivities. Although non-glycosylated marker allergens would facilitate the identification of the culprit venom, the major allergen phospholipase A1 (Ves v 1) from yellow jacket venom (YJV) remained unavailable so far. Methods Expression of Ves v 1 as wild type and enzymatically inactivated mutant and Ves v 5 in insect cells yielded soluble proteins that were purified via affinity chromatography. Functionality of the recombinant allergens was assessed by enzymatic and biophysical analyses as well as basophil activation tests. Diagnostic relevance was addressed by ELISA-based analyses of sera of YJV-sensitized patients. Results Both major allergens Ves v 1 and Ves v 5 could be produced in insect cells in secreted soluble form. The recombinant proteins exhibited their particular biochemical and functional characteristics and were capable for activation of human basophils. Assessment of IgE reactivity of sera of YJV-sensitized and double-sensitized patients emphasised the relevance of Ves v 1 in hymenoptera venom allergy. In contrast to the use of singular molecules the combined use of both molecules enabled a reliable assignment of sensitisation to YJV for more than 90% of double-sensitised patients. Conclusions The recombinant availability of Ves v 1 from yellow jacket venom will contribute to a more detailed understanding of the molecular and allergological mechanisms of insect venoms and may provide a valuable tool for diagnostic and therapeutic approaches in hymenoptera venom allergy. PMID:20359368

  7. Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones.

    PubMed

    Moran, Yehu; Genikhovich, Grigory; Gordon, Dalia; Wienkoop, Stefanie; Zenkert, Claudia; Ozbek, Suat; Technau, Ulrich; Gurevitz, Michael

    2012-04-07

    Jellyfish, hydras, corals and sea anemones (phylum Cnidaria) are known for their venomous stinging cells, nematocytes, used for prey and defence. Here we show, however, that the potent Type I neurotoxin of the sea anemone Nematostella vectensis, Nv1, is confined to ectodermal gland cells rather than nematocytes. We demonstrate massive Nv1 secretion upon encounter with a crustacean prey. Concomitant discharge of nematocysts probably pierces the prey, expediting toxin penetration. Toxin efficiency in sea water is further demonstrated by the rapid paralysis of fish or crustacean larvae upon application of recombinant Nv1 into their medium. Analysis of other anemone species reveals that in Anthopleura elegantissima, Type I neurotoxins also appear in gland cells, whereas in the common species Anemonia viridis, Type I toxins are localized to both nematocytes and ectodermal gland cells. The nematocyte-based and gland cell-based envenomation mechanisms may reflect substantial differences in the ecology and feeding habits of sea anemone species. Overall, the immunolocalization of neurotoxins to gland cells changes the common view in the literature that sea anemone neurotoxins are produced and delivered only by stinging nematocytes, and raises the possibility that this toxin-secretion mechanism is an ancestral evolutionary state of the venom delivery machinery in sea anemones.

  8. Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones

    PubMed Central

    Moran, Yehu; Genikhovich, Grigory; Gordon, Dalia; Wienkoop, Stefanie; Zenkert, Claudia; Özbek, Suat; Technau, Ulrich; Gurevitz, Michael

    2012-01-01

    Jellyfish, hydras, corals and sea anemones (phylum Cnidaria) are known for their venomous stinging cells, nematocytes, used for prey and defence. Here we show, however, that the potent Type I neurotoxin of the sea anemone Nematostella vectensis, Nv1, is confined to ectodermal gland cells rather than nematocytes. We demonstrate massive Nv1 secretion upon encounter with a crustacean prey. Concomitant discharge of nematocysts probably pierces the prey, expediting toxin penetration. Toxin efficiency in sea water is further demonstrated by the rapid paralysis of fish or crustacean larvae upon application of recombinant Nv1 into their medium. Analysis of other anemone species reveals that in Anthopleura elegantissima, Type I neurotoxins also appear in gland cells, whereas in the common species Anemonia viridis, Type I toxins are localized to both nematocytes and ectodermal gland cells. The nematocyte-based and gland cell-based envenomation mechanisms may reflect substantial differences in the ecology and feeding habits of sea anemone species. Overall, the immunolocalization of neurotoxins to gland cells changes the common view in the literature that sea anemone neurotoxins are produced and delivered only by stinging nematocytes, and raises the possibility that this toxin-secretion mechanism is an ancestral evolutionary state of the venom delivery machinery in sea anemones. PMID:22048953

  9. Spider-venom peptides as bioinsecticides.

    PubMed

    Windley, Monique J; Herzig, Volker; Dziemborowicz, Sławomir A; Hardy, Margaret C; King, Glenn F; Nicholson, Graham M

    2012-03-01

    Over 10,000 arthropod species are currently considered to be pest organisms. They are estimated to contribute to the destruction of ~14% of the world's annual crop production and transmit many pathogens. Presently, arthropod pests of agricultural and health significance are controlled predominantly through the use of chemical insecticides. Unfortunately, the widespread use of these agrochemicals has resulted in genetic selection pressure that has led to the development of insecticide-resistant arthropods, as well as concerns over human health and the environment. Bioinsecticides represent a new generation of insecticides that utilise organisms or their derivatives (e.g., transgenic plants, recombinant baculoviruses, toxin-fusion proteins and peptidomimetics) and show promise as environmentally-friendly alternatives to conventional agrochemicals. Spider-venom peptides are now being investigated as potential sources of bioinsecticides. With an estimated 100,000 species, spiders are one of the most successful arthropod predators. Their venom has proven to be a rich source of hyperstable insecticidal mini-proteins that cause insect paralysis or lethality through the modulation of ion channels, receptors and enzymes. Many newly characterized insecticidal spider toxins target novel sites in insects. Here we review the structure and pharmacology of these toxins and discuss the potential of this vast peptide library for the discovery of novel bioinsecticides.

  10. The insecticidal potential of venom peptides.

    PubMed

    Smith, Jennifer J; Herzig, Volker; King, Glenn F; Alewood, Paul F

    2013-10-01

    Pest insect species are a burden to humans as they destroy crops and serve as vectors for a wide range of diseases including malaria and dengue. Chemical insecticides are currently the dominant approach for combating these pests. However, the de-registration of key classes of chemical insecticides due to their perceived ecological and human health risks in combination with the development of insecticide resistance in many pest insect populations has created an urgent need for improved methods of insect pest control. The venoms of arthropod predators such as spiders and scorpions are a promising source of novel insecticidal peptides that often have different modes of action to extant chemical insecticides. These peptides have been optimized via a prey-predator arms race spanning hundreds of millions of years to target specific types of insect ion channels and receptors. Here we review the current literature on insecticidal venom peptides, with a particular focus on their structural and pharmacological diversity, and discuss their potential for deployment as insecticides.

  11. Spider-Venom Peptides as Bioinsecticides

    PubMed Central

    Windley, Monique J.; Herzig, Volker; Dziemborowicz, Sławomir A.; Hardy, Margaret C.; King, Glenn F.; Nicholson, Graham M.

    2012-01-01

    Over 10,000 arthropod species are currently considered to be pest organisms. They are estimated to contribute to the destruction of ~14% of the world’s annual crop production and transmit many pathogens. Presently, arthropod pests of agricultural and health significance are controlled predominantly through the use of chemical insecticides. Unfortunately, the widespread use of these agrochemicals has resulted in genetic selection pressure that has led to the development of insecticide-resistant arthropods, as well as concerns over human health and the environment. Bioinsecticides represent a new generation of insecticides that utilise organisms or their derivatives (e.g., transgenic plants, recombinant baculoviruses, toxin-fusion proteins and peptidomimetics) and show promise as environmentally-friendly alternatives to conventional agrochemicals. Spider-venom peptides are now being investigated as potential sources of bioinsecticides. With an estimated 100,000 species, spiders are one of the most successful arthropod predators. Their venom has proven to be a rich source of hyperstable insecticidal mini-proteins that cause insect paralysis or lethality through the modulation of ion channels, receptors and enzymes. Many newly characterized insecticidal spider toxins target novel sites in insects. Here we review the structure and pharmacology of these toxins and discuss the potential of this vast peptide library for the discovery of novel bioinsecticides. PMID:22741062

  12. Antarctic Fishes.

    ERIC Educational Resources Information Center

    Eastman, Joseph T.; DeVries, Arthur L.

    1986-01-01

    Explains the adaptations to Antarctic waters that Notothenioidei, a group of advanced bony fishes, have exhibited. Discusses the fishes' mechanisms of production of antifreeze properties and their capacities for neutral buoyancy in water. (ML)

  13. Fish Allergy

    MedlinePlus

    ... Basics Facts and Statistics NIAID Resources Allergens Peanut Tree Nuts Milk Egg Wheat Soy Fish Shellfish Sesame ... Basics Facts and Statistics NIAID Resources Allergens Peanut Tree Nuts Milk Egg Wheat Soy Fish Shellfish Sesame ...

  14. Antarctic Fishes.

    ERIC Educational Resources Information Center

    Eastman, Joseph T.; DeVries, Arthur L.

    1986-01-01

    Explains the adaptations to Antarctic waters that Notothenioidei, a group of advanced bony fishes, have exhibited. Discusses the fishes' mechanisms of production of antifreeze properties and their capacities for neutral buoyancy in water. (ML)

  15. Expression pattern of three-finger toxin and phospholipase A2 genes in the venom glands of two sea snakes, Lapemis curtus and Acalyptophis peronii: comparison of evolution of these toxins in land snakes, sea kraits and sea snakes.

    PubMed

    Pahari, Susanta; Bickford, David; Fry, Bryan G; Kini, R Manjunatha

    2007-09-27

    Snake venom composition varies widely both among closely related species and within the same species, based on ecological variables. In terrestrial snakes, such variation has been proposed to be due to snakes' diet. Land snakes target various prey species including insects (arthropods), lizards (reptiles), frogs and toads (amphibians), birds (aves), and rodents (mammals), whereas sea snakes target a single vertebrate class (fishes) and often specialize on specific types of fish. It is therefore interesting to examine the evolution of toxins in sea snake venoms compared to that of land snakes. Here we describe the expression of toxin genes in the venom glands of two sea snakes, Lapemis curtus (Spine-bellied Sea Snake) and Acalyptophis peronii (Horned Sea Snake), two members of a large adaptive radiation which occupy very different ecological niches. We constructed cDNA libraries from their venom glands and sequenced 214 and 192 clones, respectively. Our data show that despite their explosive evolutionary radiation, there is very little variability in the three-finger toxin (3FTx) as well as the phospholipase A2 (PLA2) enzymes, the two main constituents of Lapemis curtus and Acalyptophis peronii venom. To understand the evolutionary trends among land snakes, sea snakes and sea kraits, pairwise genetic distances (intraspecific and interspecific) of 3FTx and PLA2 sequences were calculated. Results show that these proteins appear to be highly conserved in sea snakes in contrast to land snakes or sea kraits, despite their extremely divergent and adaptive ecological radiation. Based on these results, we suggest that streamlining in habitat and diet in sea snakes has possibly kept their toxin genes conserved, suggesting the idea that prey composition and diet breadth may contribute to the diversity and evolution of venom components.

  16. Expression pattern of three-finger toxin and phospholipase A2 genes in the venom glands of two sea snakes, Lapemis curtus and Acalyptophis peronii: comparison of evolution of these toxins in land snakes, sea kraits and sea snakes

    PubMed Central

    Pahari, Susanta; Bickford, David; Fry, Bryan G; Kini, R Manjunatha

    2007-01-01

    Background Snake venom composition varies widely both among closely related species and within the same species, based on ecological variables. In terrestrial snakes, such variation has been proposed to be due to snakes' diet. Land snakes target various prey species including insects (arthropods), lizards (reptiles), frogs and toads (amphibians), birds (aves), and rodents (mammals), whereas sea snakes target a single vertebrate class (fishes) and often specialize on specific types of fish. It is therefore interesting to examine the evolution of toxins in sea snake venoms compared to that of land snakes. Results Here we describe the expression of toxin genes in the venom glands of two sea snakes, Lapemis curtus (Spine-bellied Sea Snake) and Acalyptophis peronii (Horned Sea Snake), two members of a large adaptive radiation which occupy very different ecological niches. We constructed cDNA libraries from their venom glands and sequenced 214 and 192 clones, respectively. Our data show that despite their explosive evolutionary radiation, there is very little variability in the three-finger toxin (3FTx) as well as the phospholipase A2 (PLA2) enzymes, the two main constituents of Lapemis curtus and Acalyptophis peronii venom. To understand the evolutionary trends among land snakes, sea snakes and sea kraits, pairwise genetic distances (intraspecific and interspecific) of 3FTx and PLA2 sequences were calculated. Results show that these proteins appear to be highly conserved in sea snakes in contrast to land snakes or sea kraits, despite their extremely divergent and adaptive ecological radiation. Conclusion Based on these results, we suggest that streamlining in habitat and diet in sea snakes has possibly kept their toxin genes conserved, suggesting the idea that prey composition and diet breadth may contribute to the diversity and evolution of venom components. PMID:17900344

  17. Fish Dishes.

    ERIC Educational Resources Information Center

    Derby, Marie

    2003-01-01

    Describes an art project that was inspired by Greek pottery, specifically dishes shaped as fish. Explains that fourth-grade students drew a fish shape that was later used to create their clay version of the fish. Discusses how the students examined the pottery to make decisions about color and design. (CMK)

  18. Fish Dishes.

    ERIC Educational Resources Information Center

    Derby, Marie

    2003-01-01

    Describes an art project that was inspired by Greek pottery, specifically dishes shaped as fish. Explains that fourth-grade students drew a fish shape that was later used to create their clay version of the fish. Discusses how the students examined the pottery to make decisions about color and design. (CMK)

  19. The venomous cocktail of the vampire snail Colubraria reticulata (Mollusca, Gastropoda).

    PubMed

    Modica, Maria Vittoria; Lombardo, Fabrizio; Franchini, Paolo; Oliverio, Marco

    2015-06-09

    Hematophagy arose independently multiple times during metazoan evolution, with several lineages of vampire animals particularly diversified in invertebrates. However, the biochemistry of hematophagy has been studied in a few species of direct medical interest and is still underdeveloped in most invertebrates, as in general is the study of venom toxins. In cone snails, leeches, arthropods and snakes, the strong target specificity of venom toxins uniquely aligns them to industrial and academic pursuits (pharmacological applications, pest control etc.) and provides a biochemical tool for studying biological activities including cell signalling and immunological response. Neogastropod snails (cones, oyster drills etc.) are carnivorous and include active predators, scavengers, grazers on sessile invertebrates and hematophagous parasites; most of them use venoms to efficiently feed. It has been hypothesized that trophic innovations were the main drivers of rapid radiation of Neogastropoda in the late Cretaceous. We present here the first molecular characterization of the alimentary secretion of a non-conoidean neogastropod, Colubraria reticulata. Colubrariids successfully feed on the blood of fishes, throughout the secretion into the host of a complex mixture of anaesthetics and anticoagulants. We used a NGS RNA-Seq approach, integrated with differential expression analyses and custom searches for putative secreted feeding-related proteins, to describe in detail the salivary and mid-oesophageal transcriptomes of this Mediterranean vampire snail, with functional and evolutionary insights on major families of bioactive molecules. A remarkably low level of overlap was observed between the gene expression in the two target tissues, which also contained a high percentage of putatively secreted proteins when compared to the whole body. At least 12 families of feeding-related proteins were identified, including: 1) anaesthetics, such as ShK Toxin-containing proteins and

  20. Biotechnological applications of brown spider (Loxosceles genus) venom toxins.

    PubMed

    Senff-Ribeiro, Andrea; Henrique da Silva, Paulo; Chaim, Olga Meiri; Gremski, Luiza Helena; Paludo, Kátia Sabrina; Bertoni da Silveira, Rafael; Gremski, Waldemiro; Mangili, Oldemir Carlos; Veiga, Silvio Sanches

    2008-01-01

    Loxoscelism (the term used to define accidents by the bite of brown spiders) has been reported worldwide. Clinical manifestations following brown spider bites are frequently associated with skin degeneration, a massive inflammatory response at the injured region, intravascular hemolysis, platelet aggregation causing thrombocytopenia and renal disturbances. The mechanisms by which the venom exerts its noxious effects are currently under investigation. The whole venom is a complex mixture of toxins enriched with low molecular mass proteins in the range of 5-40 kDa. Toxins including alkaline phosphatase, hyaluronidase, metalloproteases (astacin-like proteases), low molecular mass (5.6-7.9 kDa) insecticidal peptides and phospholipases-D (dermonecrotic toxins) have been identified in the venom. The purpose of the present review is to describe biotechnological applications of whole venom or some toxins, with especial emphasis upon molecular biology findings obtained in the last years.

  1. Peptidomic and transcriptomic profiling of four distinct spider venoms

    PubMed Central

    Oldrati, Vera; Koua, Dominique; Allard, Pierre-Marie; Hulo, Nicolas; Arrell, Miriam; Nentwig, Wolfgang; Lisacek, Frédérique; Wolfender, Jean-Luc; Kuhn-Nentwig, Lucia; Stöcklin, Reto

    2017-01-01

    Venom based research is exploited to find novel candidates for the development of innovative pharmacological tools, drug candidates and new ingredients for cosmetic and agrochemical industries. Moreover, venomics, as a well-established approach in systems biology, helps to elucidate the genetic mechanisms of the production of such a great molecular biodiversity. Today the advances made in the proteomics, transcriptomics and bioinformatics fields, favor venomics, allowing the in depth study of complex matrices and the elucidation even of minor compounds present in minute biological samples. The present study illustrates a rapid and efficient method developed for the elucidation of venom composition based on NextGen mRNA sequencing of venom glands and LC-MS/MS venom proteome profiling. The analysis of the comprehensive data obtained was focused on cysteine rich peptide toxins from four spider species originating from phylogenetically distant families for comparison purposes. The studied species were Heteropoda davidbowie (Sparassidae), Poecilotheria formosa (Theraphosidae), Viridasius fasciatus (Viridasiidae) and Latrodectus mactans (Theridiidae). This led to a high resolution profiling of 284 characterized cysteine rich peptides, 111 of which belong to the Inhibitor Cysteine Knot (ICK) structural motif. The analysis of H. davidbowie venom revealed a high richness in term of venom diversity: 95 peptide sequences were identified; out of these, 32 peptides presented the ICK structural motif and could be classified in six distinct families. The profiling of P. formosa venom highlighted the presence of 126 peptide sequences, with 52 ICK toxins belonging to three structural distinct families. V. fasciatus venom was shown to contain 49 peptide sequences, out of which 22 presented the ICK structural motif and were attributed to five families. The venom of L. mactans, until now studied for its large neurotoxins (Latrotoxins), revealed the presence of 14 cysteine rich

  2. Soluble copolymer of wasp venom with human albumin for venom immunotherapy.

    PubMed

    Gewurz, A; Grammer, L C; Shaughnessy, M A; Patterson, R

    1986-03-01

    Polymerization of allergens decreases allergenicity while retaining immunogenicity, as we have demonstrated for ragweed, grass, and tree pollens. We have also polymerized bee venom with human albumin to form soluble, high-molecular-weight copolymers that are immunogenic in rabbits. We now have prepared a soluble wasp venom-albumin polymer (WVAP), molecular weight greater than or equal to 240,000 daltons, by glutaraldehyde treatment and Sephacryl S-300 column fractionation. Rabbits immunized with WVAP produced IgG to both WVAP and wasp venom (WV), as measured by ELISA. IgG against WVAP was totally inhibitable by a mixture of WV and albumin, demonstrating both retention of native antigens and absence of new antigenic determinants in WVAP. IgG against WV in serum from patients receiving maintenance doses of WV immunotherapy was inhibited by WVAP. In summary, we have synthesized a soluble, high-molecular-weight copolymer of WV that retains the immunogenicity of native WV, contains no new antigenic determinants, and has potential value in the treatment of patients with WV anaphylaxis.

  3. Efficient muscle regeneration after highly haemorrhagic Bothrops alternatus venom injection.

    PubMed

    Garcia Denegri, María Emilia; Teibler, Gladys P; Maruñak, Silvana L; Hernández, David R; Acosta, Ofelia C; Leiva, Laura C

    2016-11-01

    Bothrops alternatus snake venom is particularly characterized for inducing a prominent haemorrhage and affecting hemostasis as a consequence of 43.1% of metallo-proteinases and less than 10% of PLA2 (almost all non-myotoxic phospholipases) in its venomics. In addition, myonecrosis is the major local effect in viper envenoming which might lead to permanent sequela. Then, the rebuilding of the microvasculature at the local injured site acquires significance since represents one of the pivotal stages for subsequent skeletal muscle regeneration either at morphological or functional aspects. Due to the significance played by vasculature in this process, it is important to study by histology and immunohistochemical techniques, the muscular damage and the sequence of skeletal muscle reconstruction (degree of damage, reconstitution of muscle fibres and capillaries). In this work, we injected intramuscularly 50 or 100 μg per mouse of B. alternatus venom in gastrocnemius muscles. We provided a complete description and characterization of the different stages of myogenesis after mild (50 µg) and severe (100 µg) local injury induced by B. alternatus venom toxins. The regeneration was evaluated 24 h, 3, 7, 14 and 28 days after receiving venom injection. Finally, both doses induced an extended necrosis at the site of injection where, when critical steps in the regenerative process are taking place, an efficient tissue rebuilding is achieved. B. alternatus venom is characterized by the high percentage of exclusively class P-III metalloproteinases, and by the lack of class P-I metalloproteinases in its venom composition. This could explain the effectiveness of muscle regeneration after venom injection despite the severity of the initial phase of envenoming.

  4. Venom yields from Australian and some other species of snakes.

    PubMed

    Mirtschin, Peter J; Dunstan, Nathan; Hough, Ben; Hamilton, Ewan; Klein, Sharna; Lucas, Jonathan; Millar, David; Madaras, Frank; Nias, Timothy

    2006-08-01

    The wet and dry venom yields for most Australian native dangerous snakes and a number of non-Australian species are presented. Snakes from the Pseudonaja genus yielded higher than previously published amounts and suggest reconsideration be given to increasing the volume of antivenom in each vial. Higher percentage solids were obtained from venoms from the 4 cobra species (Naja) and Pseudechis genus included in this series.

  5. Venom allergy testing: is a graded approach necessary?

    PubMed

    Quirt, Jaclyn A; Wen, Xia; Kim, Jonathan; Herrero, Angel Jimenez; Kim, Harold L

    2016-01-01

    Many institutions recommend a stepwise approach to intradermal testing for venom allergy. This is costly and uncomfortable for the patient. The rationale for this approach is the risk of potential adverse reactions to testing with the maximal dose alone. To evaluate the safety of a single-step approach to venom allergy testing. The authors retrospectively reviewed the charts of 300 consecutive patients with suspected hymenoptera venom allergy based on history who underwent venom allergy testing in a single allergist's clinic where a single-step protocol had been adopted. All patients had positive skin test reaction to at least 1 hymenoptera venom. Charts were reviewed for testing protocol used, results of testing, and reported immediate and delayed adverse reactions to testing. All patients underwent testing with an identical single-step protocol with an intradermal dose of 0.02 mL of a 1.0-μg/mL concentration of each of the 5 commercially available vespid and bee venoms. Only 1 patient reported an adverse reaction to testing, which was delayed until the morning after his visit. There were no immediate adverse reactions. The patient who had the delayed reaction was successfully started on venom immunotherapy subsequent to his reaction. A single-step venom allergy intradermal testing protocol with a 1.0-μg/mL concentration of commercially available extracts is a safe option, which, if adopted into practice, could lead to more streamlined care for patients and cost savings for the medical system. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Cone venom--from accidental stings to deliberate injection.

    PubMed

    McIntosh, J M; Jones, R M

    2001-10-01

    Cone snails have long been of note due to their colorful shells and deadly venom. Over the years, a number of people who have encountered these molluscs have been injured or killed by their sting. Biochemical analysis of the venom components has revealed a plethora of peptides and proteins that target a variety of receptors and ion channels. Pharmaceutical companies are now utilizing the selectivity and potency of Conus-derived peptides to develop novel medications for pain, epilepsy and other disorders.

  7. Neuromuscular activity of Bothrops fonsecai snake venom in vertebrate preparations

    PubMed Central

    Fernandes, Carla T; Giaretta, Vânia MA; Prudêncio, Luiz S; Toledo, Edvana O; da Silva, Igor RF; Collaço, Rita CO; Barbosa, Ana M; Hyslop, Stephen; Rodrigues-Simioni, Léa; Cogo, José C

    2014-01-01

    The neuromuscular activity of venom from Bothrops fonsecai, a lancehead endemic to southeastern Brazil, was investigated. Chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND) preparations were used for myographic recordings and mouse diaphragm muscle was used for membrane resting potential (RP) and miniature end-plate potential (MEPP) recordings. Creatine kinase release and muscle damage were also assessed. In CBC, venom (40, 80 and 160μg/ml) produced concentration- and time-dependent neuromuscular blockade (50% blockade in 85±9 min and 73±8 min with 80 and 160μg/ml, respectively) and attenuated the contractures to 110μM ACh (78–100% inhibition) and 40mM KCl (45–90% inhibition). The venom-induced decrease in twitch-tension in curarized, directly-stimulated preparations was similar to that in indirectly stimulated preparations. Venom (100 and 200μg/ml) also caused blockade in PND preparations (50% blockade in 94±13 min and 49±8 min with 100 and 200μg/ml, respectively) but did not alter the RP or MEPP amplitude. In CBC, venom caused creatine kinase release and myonecrosis. The venom-induced decrease in twitch-tension and in the contractures to ACh and K+ were abolished by preincubating venom with commercial antivenom. These findings indicate that Bothrops fonsecai venom interferes with neuromuscular transmission essentially through postsynaptic muscle damage that affects responses to ACh and KCl. These actions are effectively prevented by commercial antivenom. PMID:25028603

  8. Venoms, copper, and zinc in the treatment of arthritis.

    PubMed

    Caldwell, J R

    1999-11-01

    This article discusses the use of venoms, copper, and zinc in the treatment of arthritis. The author examines the history and effectiveness of viper, bee, and ant venoms in order to determine whether these natural ingredients in anti-inflammatory medications help relieve a patient's symptoms. Copper and zinc studies may offer therapeutic benefits, but there is still no solid consensus on the potential role of these elements in treating arthritis.

  9. The venom-gland transcriptome of the eastern coral snake (Micrurus fulvius) reveals high venom complexity in the intragenomic evolution of venoms.

    PubMed

    Margres, Mark J; Aronow, Karalyn; Loyacano, Jacob; Rokyta, Darin R

    2013-08-02

    Snake venom is shaped by the ecology and evolution of venomous species, and signals of positive selection in toxins have been consistently documented, reflecting the role of venoms as an ecologically critical phenotype. New World coral snakes (Elapidae) are represented by three genera and over 120 species and subspecies that are capable of causing significant human morbidity and mortality, yet coral-snake venom composition is poorly understood in comparison to that of Old World elapids. High-throughput sequencing is capable of identifying thousands of loci, while providing characterizations of expression patterns and the molecular evolutionary forces acting within the venom gland. We describe the de novo assembly and analysis of the venom-gland transcriptome of the eastern coral snake (Micrurus fulvius). We identified 1,950 nontoxin transcripts and 116 toxin transcripts. These transcripts accounted for 57.1% of the total reads, with toxins accounting for 45.8% of the total reads. Phospholipases A(2) and three-finger toxins dominated expression, accounting for 86.0% of the toxin reads. A total of 15 toxin families were identified, revealing venom complexity previously unknown from New World coral snakes. Toxins exhibited high levels of heterozygosity relative to nontoxins, and overdominance may favor gene duplication leading to the fixation of advantageous alleles. Phospholipase A(2) expression was uniformly distributed throughout the class while three-finger toxin expression was dominated by a handful of transcripts, and phylogenetic analyses indicate that toxin divergence may have occurred following speciation. Positive selection was detected in three of the four most diverse toxin classes, suggesting that venom diversification is driven by recurrent directional selection. We describe the most complete characterization of an elapid venom gland to date. Toxin gene duplication may be driven by heterozygote advantage, as the frequency of polymorphic toxin loci was

  10. California ground squirrel (Spermophilus beecheyi) defenses against rattlesnake venom digestive and hemostatic toxins.

    PubMed

    Biardi, James E; Chien, David C; Coss, Richard G

    2006-01-01

    Previous studies have shown that some mammals are able to neutralize venom from snake predators. California ground squirrels (Spermophilus beecheyi) show variation among populations in their ability to bind venom and minimize damage from northern Pacific rattlesnakes (Crotalus oreganus), but the venom toxins targeted by resistance have not been investigated. Four California ground squirrel populations, selected for differences in local density or type of rattlesnake predators, were assayed for their ability to neutralize digestive and hemostatic effects of venom from three rattlesnake species. In Douglas ground squirrels (S. b. douglasii), we found that animals from a location where snakes are common showed greater inhibition of venom metalloprotease and hemolytic activity than animals from a location where snakes are rare. Effects on general proteolysis were not different. Douglas ground squirrels also reduced the metalloprotease activity of venom from sympatric northern Pacific rattlesnakes (C. o. oreganus) more than the activity of venom from allopatric western diamondback rattlesnakes (C. atrox), but enhanced the fibrinolysis of sympatric venom almost 1.8 times above baseline levels. Two Beechey ground squirrel (S. b. beecheyi) populations had similar inhibition of venoms from northern and southern Pacific rattlesnakes (C. o. helleri), despite differences between the populations in the locally prevalent predator. However, the venom toxins inhibited by Beechey squirrels varied among venom from Pacific rattlesnake subspecies, and between these venoms and venom from allopatric western diamondback rattlesnakes. Blood plasma from Beechey squirrels showed highest inhibition of metalloprotease activity of northern Pacific rattlesnake venom, general proteolytic activity and hemolysis of southern Pacific rattlesnake venom, and hemolysis by allopatric western diamondback venom. These results reveal previously cryptic variation in venom activity against resistant prey

  11. California ground squirrel (Spermophilus beecheyi) defenses against rattlesnake venom digestive and hemostatic toxins.

    PubMed

    Biardi, James E; Chien, David C; Coss, Richard G

    2005-11-01

    Previous studies have shown that some mammals are able to neutralize venom from snake predators. California ground squirrels (Spermophilus beecheyi) show variation among populations in their ability to bind venom and minimize damage from northern Pacific rattlesnakes (Crotalus oreganus), but the venom toxins targeted by resistance have not been investigated. Four California ground squirrel populations, selected for differences in local density or type of rattlesnake predators, were assayed for their ability to neutralize digestive and hemostatic effects of venom from three rattlesnake species. In Douglas ground squirrels (S. b. douglasii), we found that animals from a location where snakes are common showed greater inhibition of venom metalloprotease and hemolytic activity than animals from a location where snakes are rare. Effects on general proteolysis were not different. Douglas ground squirrels also reduced the metalloprotease activity of venom from sympatric northern Pacific rattlesnakes (Crotalus oreganus oreganus) more than the activity of venom from allopatric western diamondback rattlesnakes (C. atrox), but enhanced fibrinolysis of sympatric venom almost 1.8 times above baseline levels. Two Beechey ground squirrel (S. b. beecheyi) populations had similar inhibition of venoms from northern and southern Pacific rattlesnakes (C. o. helleri), despite differences between the populations in the locally prevalent predator. However, the venom toxins inhibited by Beechey squirrels did vary among venom from Pacific rattlesnake subspecies, and between these venoms and venom from allopatric western diamondback rattlesnakes. Blood plasma from Beechey squirrels showed highest inhibition of metalloprotease activity of northern Pacific rattlesnake venom, general proteolytic activity and hemolysis of southern Pacific rattlesnake venom, and hemolysis by allopatric western diamondback venom. These results reveal previously cryptic variation in venom activity against

  12. The first report on transcriptome analysis of the venom gland of Iranian scorpion, Hemiscorpius lepturus.

    PubMed

    Kazemi-Lomedasht, Fatemeh; Khalaj, Vahid; Bagheri, Kamran Pooshang; Behdani, Mahdi; Shahbazzadeh, Delavar

    2017-01-01

    Hemiscorpius lepturus scorpion is one of the most venomous members of the Hemiscorpiidae family. H. lepturus is distributed in Iran, Iraq and Yemen. The prevalence and severity of scorpionism is high and health services are not able to control it. Scorpionism in Iran especially in the southern regions (Khuzestan, Sistan and Baluchestan, Hormozgan, Ilam) is one of the main health challenges. Due to the medical and health importance of scorpionism, the focus of various studies has been on the identification of H. lepturus venom components. Nevertheless, until now, only a few percent of H. lepturus venom components have been identified and there is no complete information about the venom components of H. lepturus. The current study reports transcriptome analysis of the venom gland of H. lepturus scorpion. Illumina Next Generation Sequencing results identified venom components of H. lepturus. When compared with other scorpion's venom, the venom of H. lepturus consists of mixtures of peptides, proteins and enzymes such as; phospholipases, metalloproteases, hyaluronidases, potassium channel toxins, calcium channel toxins, antimicrobial peptides (AMPs), venom proteins, venom toxins, allergens, La1-like peptides, proteases and scorpine-like peptides. Comparison of identified components of H. lepturus venom was carried out with venom components of reported scorpions and various identities and similarities between them were observed. With transcriptome analysis of H. lepturus venom unique sequences, coding venom components were investigated. Moreover, our study confirmed transcript expression of previously reported peptides; Hemitoxin, Hemicalcin and Hemilipin. The gene sequences of venom components were investigated employing transcriptome analysis of venom gland of H. lepturus. In summary, new bioactive molecules identified in this study, provide basis for venomics studies of scorpions of Hemiscorpiidae family and promises development of novel biotherapeutics

  13. Molecular Diversity and Gene Evolution of the Venom Arsenal of Terebridae Predatory Marine Snails.

    PubMed

    Gorson, Juliette; Ramrattan, Girish; Verdes, Aida; Wright, Elizabeth M; Kantor, Yuri; Rajaram Srinivasan, Ramakrishnan; Musunuri, Raj; Packer, Daniel; Albano, Gabriel; Qiu, Wei-Gang; Holford, Mandë

    2015-05-28

    Venom peptides from predatory organisms are a resource for investigating evolutionary processes such as adaptive radiation or diversification, and exemplify promising targets for biomedical drug development. Terebridae are an understudied lineage of conoidean snails, which also includes cone snails and turrids. Characterization of cone snail venom peptides, conotoxins, has revealed a cocktail of bioactive compounds used to investigate physiological cellular function, predator-prey interactions, and to develop novel therapeutics. However, venom diversity of other conoidean snails remains poorly understood. The present research applies a venomics approach to characterize novel terebrid venom peptides, teretoxins, from the venom gland transcriptomes of Triplostephanus anilis and Terebra subulata. Next-generation sequencing and de novo assembly identified 139 putative teretoxins that were analyzed for the presence of canonical peptide features as identified in conotoxins. To meet the challenges of de novo assembly, multiple approaches for cross validation of findings were performed to achieve reliable assemblies of venom duct transcriptomes and to obtain a robust portrait of Terebridae venom. Phylogenetic methodology was used to identify 14 teretoxin gene superfamilies for the first time, 13 of which are unique to the Terebridae. Additionally, basic local algorithm search tool homology-based searches to venom-related genes and posttranslational modification enzymes identified a convergence of certain venom proteins, such as actinoporin, commonly found in venoms. This research provides novel insights into venom evolution and recruitment in Conoidean predatory marine snails and identifies a plethora of terebrid venom peptides that can be used to investigate fundamental questions pertaining to gene evolution.

  14. Influences on venom yield in Australian tigersnakes (Notechis scutatus) and brownsnakes (Pseudonaja textilis: Elapidae, Serpentes).

    PubMed

    Mirtschin, P J; Shine, R; Nias, T J; Dunstan, N L; Hough, B J; Mirtschin, M

    2002-11-01

    The rates at which venomous animals produce venoms are of obvious biological and medical importance, but factors influencing those rates remain poorly understood. We gathered data on venom yield (wet mass of venom) and percentage solids (dry mass of the venom divided by wet mass) for 53 eastern brownsnakes (Pseudonaja textilis) and 36 mainland tigersnakes (Notechis scutatus) over a 4-year period at Venom Supplies Pty. Ltd, a commercial venom production facility in South Australia. Tigersnakes yielded about threefold more venom (by wet mass) than brownsnakes, but with slightly lower percentage solids. Both species showed significant geographic variation in percentage solids. Venom yields varied as a function of the snake's sex and geographic origin, but these effects were secondary consequences of geographic and sex-based differences in body size. Relative head size affected venom yield in brownsnakes but not tigersnakes. Overall, the amount of venom that a snake produced during milking was affected by its species, its geographic origin, its body size and relative head size, and by the time of year that it was milked, as well as by interactions among these factors. Body size was the most important effect on venom yield, with yields increasing more rapidly with size in brownsnakes than in tigersnakes. Research at the intersection of snake ecology and venom characteristics has great potential, but will require a genuinely interdisciplinary approach. Copyright 2002 Elsevier Science Ltd.

  15. Small Packages, Big Returns: Uncovering the Venom Diversity of Small Invertebrate Conoidean Snails.

    PubMed

    Gorson, J; Holford, M

    2016-11-01

    Venomous organisms used in research were historically chosen based on size and availability. This opportunity-driven strategy created a species bias in which snakes, scorpions, and spiders became the primary subjects of venom research. Increasing technological advancements have enabled interdisciplinary studies using genomics, transcriptomics, and proteomics to expand venom investigation to animals that produce small amounts of venom or lack traditional venom producing organs. One group of non-traditional venomous organisms that have benefitted from the rise of -omic technologies is the Conoideans. The Conoidean superfamily of venomous marine snails includes, the Terebridae, Turridae (s.l), and Conidae. Conoidea venom is used for both predation and defense, and therefore under strong selection pressures. The need for conoidean venom peptides to be potent and specific to their molecular targets has made them important tools for investigating cellular physiology and bioactive compounds that are beneficial to improving human health. A convincing case for the potential of Conoidean venom is made with the first commercially available conoidean venom peptide drug Ziconotide (Prialt®), an analgesic derived from Conus magus venom that is used to treat chronic pain in HIV and cancer patients. Investigation of conoidean venom using -omics technology provides significant insights into predator-driven diversification in biodiversity and identifies novel compounds for manipulating cellular communication, especially as it pertains to disease and disorders. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.

  16. Detection and neutralization of cobra venom using rabbit antiserum in experimental envenomated mice.

    PubMed

    Venkatesan, C; Sarathi, M; Balasubramanian, G; Saravanan, A; Vimal, S; Madan, N; Majeed, S Abdul; Raj, N Sundar; Hameed, A S Sahul; Babu, V Sarath

    2014-07-01

    A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to detect the venom of Indian cobra (Naja naja naja) in various tissues (brain, heart, lungs, liver, spleen, blood, kidneys, and tissue at the site of injection) of mice after cobra venom injected at different time intervals (0, 2, 4, 6, 8, and 12 h intervals up to 24 h). Whole venom antiserum or individual venom protein antiserum (14, 29, 65, 72, and 99 kDa) could recognize N. n. naja venom by Western blotting and ELISA, and antibody titer was also assayed by ELISA. Antiserum raised against cobra venom in rabbit significantly neutralized the toxicity of venom-injected mice at different time intervals after treatment. The assay could detect N. n. naja venom levels up to 2.5 ng/ml of tissue homogenate, and the venom was detected up to 24 h after venom injection. Venom was detected in brain, heart, lungs, liver, spleen, kidneys, tissue at the bite area, and blood. As observed in mice, tissue at the site of bite area showed the highest concentration of venom and the brain showed the least. Moderate amounts of venoms were found in liver, spleen, kidneys, heart, and lungs. Development of a simple, rapid, and species-specific diagnostic kit based on this ELISA technique useful to clinicians is discussed. © The Author(s) 2014.

  17. IgY antibodies anti-Tityus caripitensis venom: purification and neutralization efficacy.

    PubMed

    Alvarez, Aurora; Montero, Yuyibeth; Jimenez, Eucarys; Zerpa, Noraida; Parrilla, Pedro; Malavé, Caridad

    2013-11-01

    Tityus caripitensis is responsible for most of scorpion stings related to human incidents in Northeastern Venezuela. The only treatment for scorpion envenomation is immunotherapy based on administration of scorpion anti-venom produced in horses. Avian antibodies (IgY) isolated from chicken egg yolks represent a new alternative to be applied as anti-venom therapy. For this reason, we produced IgY antibodies against T. caripitensis scorpion venom and evaluated its neutralizing capacity. The anti-scorpion venom antibodies were purified by precipitation techniques with polyethylene glycol and evaluated by Multiple Antigen Blot Assay (MABA), an indirect ELISA, and Western blot assays. The lethality neutralization was evaluated by preincubating the venom together with the anti-venom prior to testing. The IgY immunoreactivity was demonstrated by a dose-dependent inhibition in Western blot assays where antibodies pre-absorbed with the venom did not recognize the venom proteins from T. caripitensis. The anti-venom was effective in neutralizing 2LD50 doses of T. caripitensis venom (97.8 mg of IgY neutralized 1 mg of T. caripitensis venom). Our results support the future use of avian anti-scorpion venom as an alternative to conventional equine anti-venom therapy in our country. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Venomic Analysis of the Poorly Studied Desert Coral Snake, Micrurus tschudii tschudii, Supports the 3FTx/PLA₂ Dichotomy across Micrurus Venoms.

    PubMed

    Sanz, Libia; Pla, Davinia; Pérez, Alicia; Rodríguez, Yania; Zavaleta, Alfonso; Salas, Maria; Lomonte, Bruno; Calvete, Juan J

    2016-06-07

    The venom proteome of the poorly studied desert coral snake Micrurus tschudii tschudii was unveiled using a venomic approach, which identified ≥38 proteins belonging to only four snake venom protein families. The three-finger toxins (3FTxs) constitute, both in number of isoforms (~30) and total abundance (93.6% of the venom proteome), the major protein family of the desert coral snake venom. Phospholipases A₂ (PLA₂s; seven isoforms, 4.1% of the venom proteome), 1-3 Kunitz-type proteins (1.6%), and 1-2 l-amino acid oxidases (LAO, 0.7%) complete the toxin arsenal of M. t. tschudii. Our results add to the growing evidence that the occurrence of two divergent venom phenotypes, i.e., 3FTx- and PLA₂-predominant venom proteomes, may constitute a general trend across the cladogenesis of Micrurus. The occurrence of a similar pattern of venom phenotypic variability among true sea snake (Hydrophiinae) venoms suggests that the 3FTx/PLA₂ dichotomy may be widely distributed among Elapidae venoms.

  19. Integrated Venomics and Venom Gland Transcriptome Analysis of Juvenile and Adult Mexican Rattlesnakes Crotalus simus, C. tzabcan, and C. culminatus Revealed miRNA-modulated Ontogenetic Shifts.

    PubMed

    Durban, Jordi; Sanz, Libia; Trevisan-Silva, Dilza; Neri-Castro, Edgar; Alagón, Alejandro; Calvete, Juan J

    2017-09-01

    Adult rattlesnakes within genus Crotalus express one of two distinct venom phenotypes, type I (hemorrhagic) and type II (neurotoxic). In Costa Rican Central American rattlesnake, ontogenetic changes in the concentration of miRNAs modulate venom type II to type I transition. Venomics and venom gland transcriptome analyses showed that adult C. simus and C. tzabcan expressed intermediate patterns between type II and type I venoms, whereas C. culminatus had a canonical type I venom. Neonate/juvenile and adult Mexican rattlesnakes showed notable inter- and intraspecific variability in the number, type, abundance and ontogenetic shifts of the transcriptional and translational venom gland activities. These results support a role for miRNAs in the ontogenetic venom compositional changes in the three congeneric Mexican rattlesnakes. It is worth noting the finding of dual-action miRNAs, which silence the translation of neurotoxic heterodimeric PLA2 crotoxin and acidic PLA2 mRNAs while simultaneously up-regulating SVMP-targeting mRNAs. Dual transcriptional regulation potentially explains the existence of mutually exclusive crotoxin-rich (type-II) and SVMP-rich (type-I) venom phenotypic dichotomy among rattlesnakes. Our results support the hypothesis that alterations of the distribution of miRNAs, modulating the translational activity of venom gland toxin-encoding mRNAs in response to an external cue, may contribute to the mechanism generating adaptive venom variability.

  20. Venomic Analysis of the Poorly Studied Desert Coral Snake, Micrurus tschudii tschudii, Supports the 3FTx/PLA2 Dichotomy across Micrurus Venoms

    PubMed Central

    Sanz, Libia; Pla, Davinia; Pérez, Alicia; Rodríguez, Yania; Zavaleta, Alfonso; Salas, Maria; Lomonte, Bruno; Calvete, Juan J.

    2016-01-01

    The venom proteome of the poorly studied desert coral snake Micrurus tschudii tschudii was unveiled using a venomic approach, which identified ≥38 proteins belonging to only four snake venom protein families. The three-finger toxins (3FTxs) constitute, both in number of isoforms (~30) and total abundance (93.6% of the venom proteome), the major protein family of the desert coral snake venom. Phospholipases A2 (PLA2s; seven isoforms, 4.1% of the venom proteome), 1–3 Kunitz-type proteins (1.6%), and 1–2 l-amino acid oxidases (LAO, 0.7%) complete the toxin arsenal of M. t. tschudii. Our results add to the growing evidence that the occurrence of two divergent venom phenotypes, i.e., 3FTx- and PLA2-predominant venom proteomes, may constitute a general trend across the cladogenesis of Micrurus. The occurrence of a similar pattern of venom phenotypic variability among true sea snake (Hydrophiinae) venoms suggests that the 3FTx/PLA2 dichotomy may be widely distributed among Elapidae venoms. PMID:27338473

  1. Proteomic, toxicological and immunogenic characterization of Mexican west-coast rattlesnake (Crotalus basiliscus) venom and its immunological relatedness with the venom of Central American rattlesnake (Crotalus simus).

    PubMed

    Segura, Álvaro; Herrera, María; Reta Mares, Francisco; Jaime, Claudia; Sánchez, Andrés; Vargas, Mariángela; Villalta, Mauren; Gómez, Aarón; Gutiérrez, José María; León, Guillermo

    2017-03-31

    The venom of the Mexican west-coast rattlesnake (Crotalus basiliscus) was characterized for its protein composition, toxicological profile and immunogenic properties. This venom is composed of 68% Zn(2+)-dependent metalloproteinases (SVMPs), 14% phospholipases A2 (PLA2s), 11% serine proteinases, 4% SVMPs-inhibitor tripeptides (SVMP-ITs), 2% bradykinin-potentiating peptides (BPPs), 0.6% cysteine-rich secretory proteins (CRISPs), and 0.2% l-amino acid oxidases (LAAOs). SVMPs present in the venom are responsible for azocasein hydrolysis and hemorrhagic activity, but their contribution to the lethal activity of the venom in mice is masked by the neurotoxic activity of PLA2s, which in addition are also responsible for myotoxic activity. Despite its relatively high content of serine proteinases, the venom of C. basiliscus did not exert in vitro coagulant or in vivo defibrinogenating activities. The ability of antivenoms raised against the venoms of C. basiliscus and C. simus (from Costa Rica) to neutralize homologous and heterologous venoms revealed antigenic similarities between toxins of both venoms. Preclinical evaluation of an antivenom produced by using the venom of C. basiliscus as immunogen demonstrated that it is able to neutralize not only the most relevant toxic activities of C. basiliscus venom, but also those exerted by Costa Rican C. simus venom, including coagulant and defibrinogenating activities.

  2. Characterization of a Venom Peptide from a Crassispirid Gastropod

    PubMed Central

    Cabang, April B.; Imperial, Julita S.; Gajewiak, Joanna; Watkins, Maren; Corneli, Patrice Showers; Olivera, Baldomero M.; Concepcion, Gisela P.

    2011-01-01

    The crassispirids are a large branch of venomous marine gastropods whose venoms have not been investigated previously. We demonstrate that crassispirids comprise a major group of toxoglossate snails in a clade distinct from all turrids whose venoms have been analyzed. The isolation and biochemical definition of the first venom component from any crassispirid is described. Crassipeptide cce9a from Crassispira cerithina (Anton, 1838) was purified from crude venom by following biological activity elicited in young mice, lethargy and a lack of responsiveness to external stimuli. Using Edman sequencing and mass spectrometry, the purified peptide was shown to be 29 amino acid residues long, with the sequence: GSCGLPCHENRRCGWACYCDDGICKPLRV. The sequence assignment was verified through the analysis of a cDNA clone encoding the peptide. The peptide was chemically synthesized and folded; the synthetic peptide was biologically active and coelution with the native venom peptide was demonstrated. When injected into mice of various ages, the peptide elicited a striking shift in behavioral phenotype between 14 and 16 days, from lethargy to hyperactivity. PMID:21939682

  3. Pseudechis guttatus venom proteome: Insights into evolution and toxin clustering.

    PubMed

    Viala, Vincent L; Hildebrand, Diana; Trusch, Maria; Arni, Raghuvir K; Pimenta, Daniel C; Schlüter, Hartmut; Betzel, Christian; Spencer, Patrick J

    2014-10-14

    The Australian Elapidae spotted black snake Pseudechis guttatus venom proteome composition was analyzed by high throughput mass spectrometry. The crude venom proteins were decomplexed by 2D-PAGE and in-gel digestion peptides from 66 spot samples and analyzed by tandem mass spectrometry-LC-ESI-ion trap. Protein identification was performed combining PEAKS studio 7.0 and Mascot software. The analysis identified l-amino-acid oxidases, phospholipases A2, metalloproteases, nerve growth factors and ecto-5'-nucleotidases, and for the first time in this venom the components cysteine-rich secretory proteins similar to pseudechetoxin, phospholipase B and transferrin-like protein. The envenomation symptoms are in agreement with the identified components, but the present limitations of database information might impair the detection of toxin families, protein species and still unknown toxins. From the qualitative point of view, the similarity of this venom with the ones from other Pseudechis species could be assigned to recent speciation events. Studies on the proteome of Australian Elapidae (Ancanthophiinae) are quite rare. In the present work we performed, using classic proteomic methods, a qualitative and partial analysis of the proteic components of Pseudechis guttatus venom. Although previous studies contributed to the knowledge of the major components of this venom, our study revealed some yet undescribed protein species, as well as new toxins, such as CRiSPs, phospholipase B, transferrin-like protein and ecto 5'-nucleotidase. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Snake Venom: From Deadly Toxins to Life-saving Therapeutics.

    PubMed

    Waheed, Humera; Moin, Syed F; Choudhary, M I

    2017-01-01

    Snakes are fascinating creatures and have been residents of this planet well before ancient humans dwelled the earth. Venomous snakes have been a figure of fear, and cause notable mortality throughout the world. The venom constitutes families of proteins and peptides with various isoforms that make it a cocktail of diverse molecules. These biomolecules are responsible for the disturbance in fundamental physiological systems of the envenomed victim, leading to morbidity which can lead to death if left untreated. Researchers have turned these life-threatening toxins into life-saving therapeutics via technological advancements. Since the development of captopril, the first drug that was derived from bradykininpotentiating peptide of Bothrops jararaca, to the disintegrins that have potent activity against certain types of cancers, snake venom components have shown great potential for the development of lead compounds for new drugs. There is a continuous development of new drugs from snake venom for coagulopathy and hemostasis to anti-cancer agents. In this review, we have focused on different snake venom proteins / peptides derived drugs that are in clinical use or in developmental stages till to date. Also, some commonly used snake venom derived diagnostic tools along with the recent updates in this exciting field are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Unraveling the processing and activation of snake venom metalloproteinases.

    PubMed

    Portes-Junior, José A; Yamanouye, Norma; Carneiro, Sylvia M; Knittel, Paloma S; Sant'Anna, Sávio S; Nogueira, Fabio C S; Junqueira, Magno; Magalhães, Geraldo S; Domont, Gilberto B; Moura-da-Silva, Ana M

    2014-07-03

    Snake venom metalloproteinases (SVMPs) are zinc-dependent enzymes responsible for most symptoms of human envenoming. Like matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase (ADAM) proteins, SVMPs are synthesized as zymogens, and enzyme activation is regulated by hydrolysis of their prodomain, but the processing of SVMPs is still unclear. In this study, we attempted to identify the presence of prodomain in different compartments of snake venom glands as zymogens or in the free form to elucidate some mechanism involved in SVMP activation. Using antibodies obtained by immunization with a recombinant prodomain, bands of zymogen molecular mass and prodomain peptides were detected mostly in gland extracts all along the venom production cycle and in the venom collected from the lumen at the peak of venom production. Prodomain was detected in secretory cells mostly in the secretory vesicles near the Golgi. We hypothesize that the processing of SVMPs starts within secretory vesicles and continues in the lumen of the venom gland just after enzyme secretion and involves different steps compared to ADAMs and MMPs but can be used as a model for studying the relevance of peptides resulting from prodomain processing and degradation for controlling the activity of metalloproteinases.

  6. Venom gland components of the ectoparasitoid wasp, Anisopteromalus calandrae.

    PubMed

    Perkin, Lindsey C; Friesen, Kenlee S; Flinn, Paul W; Oppert, Brenda

    2015-01-01

    The wasp Anisopteromalus calandrae is a small ectoparasitoid that attacks stored product pest beetle larvae that develop inside grain kernels, and is thus a potential insect control tool. The components of A. calandrae venom have not been studied, but venom from other organisms contains proteins with potential applications, such as pest management tools and treatments for human diseases. We dissected female A. calandrae and collected venom and associated glands. Using high throughput sequencing, a venom gland transcriptome was assembled that contained 45,432 contigs, 25,726 of which had BLASTx hits. The majority of hits were to Nasonia vitripennis, an ectoparasitoid from the same taxonomic family, as well as other bees, wasps, and ants. Gene ontology grouped sequences into eleven molecular functions, among which binding and catalytic activity had the most representatives. In this study, we highlighted the most abundant sequences, including those that are likely the functional components of the venom. Specifically, we focused on genes encoding proteins potentially involved in host developmental arrest, disrupting the host immune system, host paralysis, and transcripts that support these functions. Our report is the first to characterize components of the A. calandrae venom gland that may be useful as control tools for insect pests and other applications.

  7. Extracellular matrix molecules as targets for brown spider venom toxins.

    PubMed

    Veiga, S S; Zanetti, V C; Braz, A; Mangili, O C; Gremski, W

    2001-07-01

    Loxoscelism, the term used to describe lesions and clinical manifestations induced by brown spider's venom (Loxosceles genus), has attracted much attention over the last years. Brown spider bites have been reported to cause a local and acute inflammatory reaction that may evolve to dermonecrosis (a hallmark of envenomation) and hemorrhage at the bite site, besides systemic manifestations such as thrombocytopenia, disseminated intravascular coagulation, hemolysis, and renal failure. The molecular mechanisms by which Loxosceles venoms induce injury are currently under investigation. In this review, we focused on the latest reports describing the biological and physiopathological aspects of loxoscelism, with reference mainly to the proteases recently described as metalloproteases and serine proteases, as well as on the proteolytic effects triggered by L. intermedia venom upon extracellular matrix constituents such as fibronectin, fibrinogen, entactin and heparan sulfate proteoglycan, besides the disruptive activity of the venom on Engelbreth-Holm-Swarm basement membranes. Degradation of these extracellular matrix molecules and the observed disruption of basement membranes could be related to deleterious activities of the venom such as loss of vessel and glomerular integrity and spreading of the venom toxins to underlying tissues.

  8. Venom gland components of the ectoparasitoid wasp, Anisopteromalus calandrae

    PubMed Central

    Perkin, Lindsey C; Friesen, Kenlee S; Flinn, Paul W; Oppert, Brenda

    2015-01-01

    The wasp Anisopteromalus calandrae is a small ectoparasitoid that attacks stored product pest beetle larvae that develop inside grain kernels, and is thus a potential insect control tool. The components of A. calandrae venom have not been studied, but venom from other organisms contains proteins with potential applications, such as pest management tools and treatments for human diseases. We dissected female A. calandrae and collected venom and associated glands. Using high throughput sequencing, a venom gland transcriptome was assembled that contained 45,432 contigs, 25,726 of which had BLASTx hits. The majority of hits were to Nasonia vitripennis, an ectoparasitoid from the same taxonomic family, as well as other bees, wasps, and ants. Gene ontology grouped sequences into eleven molecular functions, among which binding and catalytic activity had the most representatives. In this study, we highlighted the most abundant sequences, including those that are likely the functional components of the venom. Specifically, we focused on genes encoding proteins potentially involved in host developmental arrest, disrupting the host immune system, host paralysis, and transcripts that support these functions. Our report is the first to characterize components of the A. calandrae venom gland that may be useful as control tools for insect pests and other applications. PMID:26998218

  9. Rapid sensitive analysis of cysteine rich peptide venom components.

    PubMed

    Ueberheide, Beatrix M; Fenyö, David; Alewood, Paul F; Chait, Brian T

    2009-04-28

    Disulfide-rich peptide venoms from animals such as snakes, spiders, scorpions, and certain marine snails represent one of nature's great diversity libraries of bioactive molecules. The various species of marine cone shells have alone been estimated to produce >50,000 distinct peptide venoms. These peptides have stimulated considerable interest because of their ability to potently alter the function of specific ion channels. To date, only a small fraction of this immense resource has been characterized because of the difficulty in elucidating their primary structures, which range in size between 10 and 80 aa, include up to 5 disulfide bonds, and can contain extensive posttranslational modifications. The extraordinary complexity of crude venoms and the lack of DNA databases for many of the organisms of interest present major analytical challenges. Here, we describe a strategy that uses mass spectrometry for the elucidation of the mature peptide toxin components of crude venom samples. Key to this strategy is our use of electron transfer dissociation (ETD), a mass spectrometric fragmentation technique that can produce sequence information across the entire peptide backbone. However, because ETD only yields comprehensive sequence coverage when the charge state of the precursor peptide ion is sufficiently high and the m/z ratio is low, we combined ETD with a targeted chemical derivatization strategy to increase the charge state of cysteine-containing peptide toxins. Using this strategy, we obtained full sequences for 31 peptide toxins, using just 7% of the crude venom from the venom gland of a single cone snail (Conus textile).

  10. Ancient Venom Systems: A Review on Cnidaria Toxins

    PubMed Central

    Jouiaei, Mahdokht; Yanagihara, Angel A.; Madio, Bruno; Nevalainen, Timo J.; Alewood, Paul F.; Fry, Bryan G.

    2015-01-01

    Cnidarians are the oldest extant lineage of venomous animals. Despite their simple anatomy, they are capable of subduing or repelling prey and predator species that are far more complex and recently evolved. Utilizing specialized penetrating nematocysts, cnidarians inject the nematocyst content or “venom” that initiates toxic and immunological reactions in the envenomated organism. These venoms contain enzymes, potent pore forming toxins, and neurotoxins. Enzymes include lipolytic and proteolytic proteins that catabolize prey tissues. Cnidarian pore forming toxins self-assemble to form robust membrane pores that can cause cell death via osmotic lysis. Neurotoxins exhibit rapid ion channel specific activities. In addition, certain cnidarian venoms contain or induce the release of host vasodilatory biogenic amines such as serotonin, histamine, bunodosine and caissarone accelerating the pathogenic effects of other venom enzymes and porins. The cnidarian attacking/defending mechanism is fast and efficient, and massive envenomation of humans may result in death, in some cases within a few minutes to an hour after sting. The complexity of venom components represents a unique therapeutic challenge and probably reflects the ancient evolutionary history of the cnidarian venom system. Thus, they are invaluable as a therapeutic target for sting treatment or as lead compounds for drug design. PMID:26094698

  11. Animal Venom Peptides: Potential for New Antimicrobial Agents.

    PubMed

    Primon-Barros, Muriel; José Macedo, Alexandre

    2017-01-01

    Microbial infections affect people worldwide, causing diseases with significant impact on public health, indicating the need for research and development of new antimicrobial agents. Animal venoms represent a vast and largely unexploited source of biologically active molecules with attractive candidates for the development of novel therapeutics. Venoms consist of complex mixtures of molecules, including antimicrobial peptides (AMPs). Since the discovery of AMPs, they have been studied as promising new antimicrobial drugs. Amongst the remarkable sources of AMPs with known antimicrobial activities are ants, bees, centipedes, cone snails, scorpions, snakes, spiders, and wasps. The antimicrobial tests against bacteria, protozoans, fungi and viruses using 170 different peptides isolated directly from crude venoms or cDNA libraries of venom glands are listed and discussed in this review, as well as hemolytic ativity. The potential of venoms as source of new compounds, including AMPs, is extensively discussed. Currently, there are six FDA-approved drugs and many others are undergoing preclinical and clinical trials. The search for antimicrobial "weapons" makes the AMPs from venoms promising candidates. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Geographical venom variations of the Southeast Asian monocled cobra (Naja kaouthia): venom-induced neuromuscular depression and antivenom neutralization.

    PubMed

    Tan, Kae Yi; Tan, Choo Hock; Sim, Si Mui; Fung, Shin Yee; Tan, Nget Hong

    2016-01-01

    The Southeast Asian monocled cobras (Naja kaouthia) exhibit geographical variations in their venom proteomes, especially on the composition of neurotoxins. This study compared the neuromuscular depressant activity of the venoms of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V), and the neutralization of neurotoxicity by a monospecific antivenom. On chick biventer cervicis nerve-muscle preparation, all venoms abolished the indirect twitches, with NK-T venom being the most potent (shortest t90, time to 90% twitch inhibition), followed by NK-V and NK-M. Acetylcholine and carbachol failed to reverse the blockade, indicating irreversible/pseudo-irreversible post-synaptic neuromuscular blockade. KCl restored the twitches variably (NK-M preparation being the least responsive), consistent with different degree of muscle damage. The findings support that NK-T venom has the most abundant curarimimetic alpha-neurotoxins, while NK-M venom contains more tissue-damaging cytotoxins. Pre-incubation of tissue with N. kaouthia monovalent antivenom (NKMAV) prevented venom-induced twitch depression, with the NK-T preparation needing the largest antivenom dose. NKMAV added after the onset of neuromuscular depression could only halt the inhibitory progression but failed to restore full contraction. The findings highlight the urgency of early antivenom administration to sequester as much circulating neurotoxins as possible, thereby hastening toxin elimination from the circulation. In envenomed mice, NKMAV administered upon the first neurological sign neutralized the neurotoxic effect, with the slowest full recovery noticed in the NK-T group. This is consistent with the high abundance of neurotoxins in the NK-T venom, implying that a larger amount or repeated dosing of NKMAV may be required in NK-T envenomation. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Venom-related transcripts from Bothrops jararaca tissues provide novel molecular insights into the production and evolution of snake venom.

    PubMed

    Junqueira-de-Azevedo, Inácio L M; Bastos, Carolina Mancini Val; Ho, Paulo Lee; Luna, Milene Schmidt; Yamanouye, Norma; Casewell, Nicholas R

    2015-03-01

    Attempts to reconstruct the evolutionary history of snake toxins in the context of their co-option to the venom gland rarely account for nonvenom snake genes that are paralogous to toxins, and which therefore represent important connectors to ancestral genes. In order to reevaluate this process, we conducted a comparative transcriptomic survey on body tissues from a venomous snake. A nonredundant set of 33,000 unigenes (assembled transcripts of reference genes) was independently assembled from six organs of the medically important viperid snake Bothrops jararaca, providing a reference list of 82 full-length toxins from the venom gland and specific products from other tissues, such as pancreatic digestive enzymes. Unigenes were then screened for nontoxin transcripts paralogous to toxins revealing 1) low level coexpression of approximately 20% of toxin genes (e.g., bradykinin-potentiating peptide, C-type lectin, snake venom metalloproteinase, snake venom nerve growth factor) in body tissues, 2) the identity of the closest paralogs to toxin genes in eight classes of toxins, 3) the location and level of paralog expression, indicating that, in general, co-expression occurs in a higher number of tissues and at lower levels than observed for toxin genes, and 4) strong evidence of a toxin gene reverting back to selective expression in a body tissue. In addition, our differential gene expression analyses identify specific cellular processes that make the venom gland a highly specialized secretory tissue. Our results demonstrate that the evolution and production of venom in snakes is a complex process that can only be understood in the context of comparative data from other snake tissues, including the identification of genes paralogous to venom toxins.

  14. Venom-Related Transcripts from Bothrops jararaca Tissues Provide Novel Molecular Insights into the Production and Evolution of Snake Venom

    PubMed Central

    Junqueira-de-Azevedo, Inácio L.M.; Bastos, Carolina Mancini Val; Ho, Paulo Lee; Luna, Milene Schmidt; Yamanouye, Norma; Casewell, Nicholas R.

    2015-01-01

    Attempts to reconstruct the evolutionary history of snake toxins in the context of their co-option to the venom gland rarely account for nonvenom snake genes that are paralogous to toxins, and which therefore represent important connectors to ancestral genes. In order to reevaluate this process, we conducted a comparative transcriptomic survey on body tissues from a venomous snake. A nonredundant set of 33,000 unigenes (assembled transcripts of reference genes) was independently assembled from six organs of the medically important viperid snake Bothrops jararaca, providing a reference list of 82 full-length toxins from the venom gland and specific products from other tissues, such as pancreatic digestive enzymes. Unigenes were then screened for nontoxin transcripts paralogous to toxins revealing 1) low level coexpression of approximately 20% of toxin genes (e.g., bradykinin-potentiating peptide, C-type lectin, snake venom metalloproteinase, snake venom nerve growth factor) in body tissues, 2) the identity of the closest paralogs to toxin genes in eight classes of toxins, 3) the location and level of paralog expression, indicating that, in general, co-expression occurs in a higher number of tissues and at lower levels than observed for toxin genes, and 4) strong evidence of a toxin gene reverting back to selective expression in a body tissue. In addition, our differential gene expression analyses identify specific cellular processes that make the venom gland a highly specialized secretory tissue. Our results demonstrate that the evolution and production of venom in snakes is a complex process that can only be understood in the context of comparative data from other snake tissues, including the identification of genes paralogous to venom toxins. PMID:25502939

  15. Immunogenicity of venoms from four common snakes in the South of Vietnam and development of ELISA kit for venom detection.

    PubMed

    Van Dong, Le; Quyen, Le Khac; Eng, Khoo Hoon; Gopalakrishnakone, P

    2003-11-01

    The antigenicity and antigenic relationship between venoms of four common snakes in the South of Vietnam-Trimeresurus popeorum, Calloselasma rhodostoma, Naja naja and Ophiophagus hannah-were studied. Most of venom components expressed antigenicity and produced high titre antivenoms. The venoms share common components and antivenoms cross-reacted along them. Furthermore, cross-reactions were observed among non-common antigens, indicating that they share common epitopes. Hence, using single component as immunogen for species diagnosis of snakebites can reduce cross-reaction, perhaps may not be totally specific. A three-step affinity purification protocol was set up for preparation of species-specific antivenom antibodies. The steps involved affinity chromatography of IgG from hyper-immunized rabbit sera with protein A columns, immuno-affinity chromatography of monovalent antivenom antibodies with respective homologous venom columns, and immuno-absorption of cross-species reacting antibody molecules with heterologous venom columns. The antibodies were then used for construction of an enzyme-linked immunosorbent assay (ELISA) test kit. The kit can differentiate among the four common snake venoms in various types of samples with the detection limit of 0.2-1.6 ng/ml, depending on the type of samples and species of the snake. The efficacy of this kit for snake venom detection was successfully demonstrated in experimental envenomation in rats. Preliminary evaluation with 140 samples taken from 88 human snakebite victims in Vietnam showed that the kit could detect venom in human samples and would be a very useful tool for fast identification of snakebites in clinics.

  16. Assessment of immunogenic characteristics of Hemiscorpius lepturus venom and its cross-reactivity with venoms from Androctonus crassicauda and Mesobuthus eupeus.

    PubMed

    Khanbashi, Shahin; Khodadadi, Ali; Assarehzadegan, Mohammad-Ali; Pipelzadeh, Mohammad Hassan; Vazirianzadeh, Babak; Hosseinzadeh, Mohsen; Rahmani, Ali Hassan; Asmar, Akbar

    2015-01-01

    Hemiscorpius lepturus (H. lepturus), one of the most venomous scorpions in tropical and sub-tropical areas, belongs to the Hemiscorpiidae family. Studies of antibodies in sera against the protein component of the venom from this organism can be of great use for the development of engineered variants of proteins for eventual use in the diagnosis/treatment of, and prevention of reactions to, stings. In the present in vitro study, the proteins of H. lepturus venom, which could specifically activate the production of immunoglobulin G (IgG) in victims accidently exposed to the venom from this scorpion, were evaluated and their cross-reactivity with venoms from two other important scorpion species including Androctonus crassicauda and Mesobuthus eupeus assessed. H. lepturus venom was analyzed with respect to its protein composition and its antigenic properties against antibodies found in sera collected from victims exposed to the venom of this scorpion within a previous 2-month period. The cross-reactivity of the H. lepturus venom with those from A. crassicauda and M. eupeus was assessed using ELISA and immunoblotting. Electrophoretic analysis of the venom of H. lepturus revealed several protein bands with weights of 8-116 KDa. The most frequent IgG-reactive bands in the test sera had weights of 34, 50, and 116 kDa. A weak cross-reactivity H. lepturus of venom with venoms from A. crassicauda and M. eupeus was detected. The results of immunoblotting and ELISA experiments revealed that H. lepturus venom activated the host immune response, leading to the production of a high titer of antibodies. Clearly, a determination of the major immunogenic components of H. lepturus venom could be valuable for future studies and ultimately of great importance for the potential production of recombinant or hypo-venom variants of these proteins.

  17. Cross-neutralization of the neurotoxicity of Crotalus durissus terrificus and Bothrops jararacussu venoms by antisera against crotoxin and phospholipase A2 from Crotalus durissus cascavella venom.

    PubMed

    Beghini, Daniela G; da Cruz-Höfling, Maria Alice; Randazzo-Moura, Priscila; Rodrigues-Simioni, Léa; Novello, José Camilo; Hyslop, Stephen; Marangoni, Sérgio

    2005-11-01

    We have previously demonstrated that rabbit antisera raised against crotoxin from Crotalus durissus cascavella venom (cdc-crotoxin) and its PLA2 (cdc-PLA2) neutralized the neurotoxicity of this venom and its crotoxin. In this study, we examined the ability of these antisera to neutralize the neurotoxicity of Crotalus durissus terrificus and Bothrops jararacussu venoms and their major toxins, cdt-crotoxin and bothropstoxin-I (BthTX-I), respectively, in mouse isolated phrenic nerve-diaphragm preparations. Immunoblotting showed that antiserum to cdc-crotoxin recognized cdt-crotoxin and BthTX-I, while antiserum to cdc-PLA2 recognized cdt-PLA2 and BthTX-I. ELISA corroborated this cross-reactivity. Antiserum to cdc-crotoxin prevented the neuromuscular blockade caused by C. d. terrificus venom and its crotoxin at a venom/crotoxin:antiserum ratio of 1:3. Antiserum to cdc-PLA2 also neutralized the neuromuscular blockade caused by C. d. terrificus venom or its crotoxin at venom or toxin:antiserum ratios of 1:3 and 1:1, respectively. The neuromuscular blockade caused by B. jararacussu venom and BthTX-I was also neutralized by the antisera to cdc-crotoxin and cdc-PLA2 at a venom/toxin:antiserum ratio of 1:10 for both. Commercial equine antivenom raised against C. d. terrificus venom was effective in preventing the neuromuscular blockade typical of B. jararacussu venom (venom:antivenom ratio of 1:2), whereas for BthTX-I the ratio was 1:10. These results show that antiserum produced against PLA2, the major toxin in C. durissus cascavella venom, efficiently neutralized the neurotoxicity of C. d. terrificus and B. jararacussu venoms and their PLA2 toxins.

  18. Hemolytic potency and phospholipase activity of some bee and wasp venoms.

    PubMed

    Watala, C; Kowalczyk, J K

    1990-01-01

    1. The action of crude venoms of four aculeate species: Apis mellifera, Vespa crabro, Vespula germanica and Vespula vulgaris on human erythrocytes was investigated in order to determine the lytic and phospholipase activity of different aculeate venoms and their ability to induce red blood cell hemolysis. 2. Bee venom was the only extract to completely lyse red blood cells at the concentration of 2-3 micrograms/ml. 3. Phospholipase activity in all of the examined vespid venoms was similar and the highest value was recorded in V. germanica. 4. Vespid venoms exhibited phospholipase B activity, which is lacking in honeybee venom. 5. In all membrane phospholipids but lecithin, lysophospholipase activity of vespid venoms was 2-6 times lower than the relevant phospholipase activity. 6. The incubation of red blood cells with purified bee venom phospholipase A2 was not accompanied by lysis and, when supplemented with purified melittin, the increase of red blood cell lysis was approximately 30%.

  19. Allergen-specific immunotherapy of Hymenoptera venom allergy - also a matter of diagnosis.

    PubMed

    Schiener, Maximilian; Graessel, Anke; Ollert, Markus; Schmidt-Weber, Carsten B; Blank, Simon

    2017-06-12

    Stings of hymenoptera can induce IgE-mediated hypersensitivity reactions in venom-allergic patients, ranging from local up to severe systemic reactions and even fatal anaphylaxis. Allergic patients' quality of life can be mainly improved by altering their immune response to tolerate the venoms by injecting increasing venom doses over years. This venom-specific immunotherapy is highly effective and well tolerated. However, component-resolved information about the venoms has increased in the last years. This knowledge is not only able to improve diagnostics as basis for an accurate therapy, but was additionally used to create tools which enable the analysis of therapeutic venom extracts on a molecular level. Therefore, during the last decade the detailed knowledge of the allergen composition of hymenoptera venoms has substantially improved diagnosis and therapy of venom allergy. This review focuses on state of the art diagnostic and therapeutic options as well as on novel directions trying to improve therapy.

  20. Detoxification of Echis ocellatus venom-induced toxicity by Annona senegalensis Pers.

    PubMed

    Emmanuel, Amlabu; Ebinbin, Ajagun; Amlabu, Wandayi

    2014-06-01

    Different fractions (I-V) of the methanolic leaf extracts of Annona senegalensis were assessed for their anti-snake venom activities. Fractions III neutralized lethal toxicity induced by Echis ocellatus venom and manifested the same potency as the crude extracts against the venom. The anti-snake venom activity of fraction III was clearly shown by the complete abrogation of venom-induced haemorrhage and the 75% record of surviving mice which were injected with a pre-incubate of venom and extract in the ratio 1:30 w/w after a 24 h. Also, fraction III exhibited a weak inhibitory effect on fibrinogen clotting activity of this venom. The key phytochemicals mediating the activity of this fraction are flavonoids and tannins. The detoxification of this venom by fraction III and the possible mode of action in the pathology of snake envenoming is discussed in this report.

  1. Venomics of the Australian eastern brown snake (Pseudonaja textilis): Detection of new venom proteins and splicing variants.

    PubMed

    Viala, Vincent Louis; Hildebrand, Diana; Trusch, Maria; Fucase, Tamara Mieco; Sciani, Juliana Mozer; Pimenta, Daniel Carvalho; Arni, Raghuvir K; Schlüter, Hartmut; Betzel, Christian; Mirtschin, Peter; Dunstan, Nathan; Spencer, Patrick Jack

    2015-12-01

    The eastern brown snake is the predominant cause of snakebites in mainland Australia. Its venom induces defibrination coagulopathy, renal failure and microangiopathic hemolytic anemia. Cardiovascular collapse has been described as an early cause of death in patients, but, so far, the mechanisms involved have not been fully identified. In the present work, we analysed the venome of Pseudonaja textilis by combining high throughput proteomics and transcriptomics, aiming to further characterize the components of this venom. The combination of these techniques in the analysis and identification of toxins, venom proteins and putative toxins allowed the sequence description and the identification of the following: prothrombinase coagulation factors, neurotoxic textilotoxin phospholipase A2 (PLA2) subunits and "acidic PLA2", three-finger toxins (3FTx) and the Kunitz-type protease inhibitor textilinin, venom metalloproteinase, C-type lectins, cysteine rich secretory proteins, calreticulin, dipeptidase 2, as well as evidences of Heloderma lizard peptides. Deep data-mining analysis revealed the secretion of a new transcript variant of venom coagulation factor 5a and the existence of a splicing variant of PLA2 modifying the UTR and signal peptide from a same mature protein. The transcriptome revealed the diversity of transcripts and mutations, and also indicates that splicing variants can be an important source of toxin variation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice

    PubMed Central

    Akahoshi, Mitsuteru; Song, Chang Ho; Piliponsky, Adrian M.; Metz, Martin; Guzzetta, Andrew; Åbrink, Magnus; Schlenner, Susan M.; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Pejler, Gunnar; Tsai, Mindy; Galli, Stephen J.

    2011-01-01

    Mast cell degranulation is important in the pathogenesis of anaphylaxis and allergic disorders. Many animal venoms contain components that can induce mast cell degranulation, and this has been thought to contribute to the pathology and mortality caused by envenomation. However, we recently reported evidence that mast cells can enhance the resistance of mice to the venoms of certain snakes and that mouse mast cell–derived carboxypeptidase A3 (CPA3) can contribute to this effect. Here, we investigated whether mast cells can enhance resistance to the venom of the Gila monster, a toxic component of that venom (helodermin), and the structurally similar mammalian peptide, vasoactive intestinal polypeptide (VIP). Using 2 types of mast cell–deficient mice, as well as mice selectively lacking CPA3 activity or the chymase mouse mast cell protease-4 (MCPT4), we found that mast cells and MCPT4, which can degrade helodermin, can enhance host resistance to the toxicity of Gila monster venom. Mast cells and MCPT4 also can limit the toxicity associated with high concentrations of VIP and can reduce the morbidity and mortality induced by venoms from 2 species of scorpions. Our findings support the notion that mast cells can enhance innate defense by degradation of diverse animal toxins and that release of MCPT4, in addition to CPA3, can contribute to this mast cell function. PMID:21926462

  3. Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice.

    PubMed

    Akahoshi, Mitsuteru; Song, Chang Ho; Piliponsky, Adrian M; Metz, Martin; Guzzetta, Andrew; Abrink, Magnus; Schlenner, Susan M; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Pejler, Gunnar; Tsai, Mindy; Galli, Stephen J

    2011-10-01

    Mast cell degranulation is important in the pathogenesis of anaphylaxis and allergic disorders. Many animal venoms contain components that can induce mast cell degranulation, and this has been thought to contribute to the pathology and mortality caused by envenomation. However, we recently reported evidence that mast cells can enhance the resistance of mice to the venoms of certain snakes and that mouse mast cell-derived carboxypeptidase A3 (CPA3) can contribute to this effect. Here, we investigated whether mast cells can enhance resistance to the venom of the Gila monster, a toxic component of that venom (helodermin), and the structurally similar mammalian peptide, vasoactive intestinal polypeptide (VIP). Using 2 types of mast cell-deficient mice, as well as mice selectively lacking CPA3 activity or the chymase mouse mast cell protease-4 (MCPT4), we found that mast cells and MCPT4, which can degrade helodermin, can enhance host resistance to the toxicity of Gila monster venom. Mast cells and MCPT4 also can limit the toxicity associated with high concentrations of VIP and can reduce the morbidity and mortality induced by venoms from 2 species of scorpions. Our findings support the notion that mast cells can enhance innate defense by degradation of diverse animal toxins and that release of MCPT4, in addition to CPA3, can contribute to this mast cell function.

  4. Anti-venom potential of aqueous extract of stem bark of Mangifera indica L. against Daboia russellii (Russell's viper) venom.

    PubMed

    Dhananjaya, B L; Zameer, F; Girish, K S; D'Souza, Cletus J M

    2011-06-01

    Several plant extracts rich in pharmacologically active compounds have shown to antagonize venom of several species. Mangifera indica has been used against snakebite by the traditional healers. However, there is paucity of scientific data in support. In this study, we evaluated the antivenom potential of aqueous extract of stem bark of M. indica against D. russellii venom-induced pharmacological effects such as life myotoxicity, edema, LD50 etc. The extract inhibited the phospholipase, protease, hyaluronidase, 5'nucleotidase, ATPase and alkaline phosphomonoesterase activities with varying IC50 values. It significantly inhibited both metalloproteases and serine proteases activities. Further, the extract significantly reduced the myotoxicity of the venom, as evident by the reduction of serum creatin kinase and lactate dehydrogenase activities. Though the extract completely inhibited in vitro PLA2 activity, it was unable to completely inhibit in situ hemolytic and in vivo edema-inducing activities, usually brought about by PLA2s. In lethality studies, co-injection of the venom preincubated with the extract showed higher protection than the independent injection of venom, followed by the extract in the mice. However, in both the cases the extract -a cocktail of inhibitors significantly increased the survival time, when compared to that of mice injected (i.p) with the venom alone. These results encourage further studies on the potential use of cocktail of inhibitors in improving the treatment of snake envenomation. Further, this study substantiates the use of M. indica as an antidote against snakebite by the traditional healers.

  5. Studies on toad venom (3): effect of metals on the quality of toad venom torrefied on a metal plate.

    PubMed

    Kawahara, Kazuhito; Mikage, Masayuki

    2002-01-01

    To study the quality of toad venom dried on different metal plates by heating at 105 degrees C, each 20 g sample of fresh toad venom collected in Hei-Long-Jiang Province, China, was dried on (1) brass, (2) copper, (3) glass, (4) acrylic resins, (5) aluminum and (6) stainless-steel, respectively. Twelve bufadienolides, including bufalin and bufotalin, in each sample were then quantitatively analyzed by HPLC. The total levels of bufadienolides in 1000.0 mg of the dried samples were (1) > (2) > (3) > (4) > (5) > (6), varying from 303.44 mg to 420.72 mg. Besides, the color of dried venom became darker in the order of (2), (4), (6), (3), (1) and (5). Though (1) was not in good color, it was superior to the others in chemical quality. These results suggest that it is possible to dry toad venom in short period by heating it at a high temperature on a tray made of brass. This will be a better method for making high quality toad venom than the traditional method. Moreover, the removal of impurities in the fresh venom by the process of filtration through silk succeeded in raising the bufadienolides content significantly.

  6. One scorpion, two venoms: Prevenom of Parabuthus transvaalicus acts as an alternative type of venom with distinct mechanism of action

    PubMed Central

    Inceoglu, Bora; Lango, Jozsef; Jing, Jie; Chen, Lili; Doymaz, Fuat; Pessah, Isaac N.; Hammock, Bruce D.

    2003-01-01

    Scorpion venom is a complex mixture of salts, small molecules, peptides, and proteins. Scorpions employ this valuable tool in several sophisticated ways for subduing prey, deterring predators, and possibly during mating. Here, a subtle but clever strategy of venom utilization by scorpions is reported. Scorpions secrete a small quantity of transparent venom when initially stimulated that we propose to name prevenom. If secretion continues, a cloudy and dense venom that is white in color is subsequently released. The prevenom contains a combination of high K+ salt and several peptides including some that block rectifying K+ channels and elicit significant pain and toxicity because of a massive local depolarization. The presence of high extracellular K+ in the prevenom can depolarize cells and also decrease the local electrochemical gradient making it more difficult to reestablish the resting potential. When this positive change to the K+ equilibrium potential is combined with the blockage of rectifying K+ channels, this further delays the recovery of the resting potential, causing a prolonged effect. We propose that the prevenom of scorpions is used as a highly efficacious predator deterrent and for immobilizing small prey while conserving metabolically expensive venom until a certain level of stimuli is reached, after which the venom is secreted. PMID:12552107

  7. Venomic analyses of Scolopendra viridicornis nigra and Scolopendra angulata (Centipede, Scolopendromorpha): shedding light on venoms from a neglected group.

    PubMed

    Rates, Breno; Bemquerer, Marcelo P; Richardson, Michael; Borges, Márcia H; Morales, Rodrigo A V; De Lima, Maria Elena; Pimenta, Adriano M C

    2007-05-01

    Centipedes are venomous arthropods responsible for a significant number of non-lethal human envenomations. Despite this, information about the composition and function of their venom contents is scarce. In this study, we have used a 'structure to function' proteomic approach combining two-dimensional chromatography (2D-LC), electrospray ionization quadrupole/time-of-flight mass spectrometry (ESI-Q-TOF/MS), N-terminal sequencing and similarity searching to better understand the complexities of the venoms from two Brazilian centipede species: Scolopendra viridicornis nigra and Scolopendra angulata. Comparisons between the LC profiles and the mass compositions of the venoms of the two species are provided. The observed molecular masses ranged from 3019.62 to 20996.94Da in S. viridicornis nigra (total: 62 molecular masses) and from 1304.73 to 22639.15Da in S. angulata (total: 65 molecular masses). Also, the N-termini of representatives of 10 protein/peptide families were successfully sequenced where nine of them showed no significant similarity to other protein sequences deposited in the Swiss-Prot database. A screening for insecto-toxic activities in fractions from S. viridicornis venom has also been performed. Six out of the 12 tested fractions were responsible for clear toxic effects in house flies. This work demonstrates that centipede venoms might be a neglected but important source of new bioactive compounds.

  8. Snake Venom Disintegrins and Cell Migration

    PubMed Central

    Selistre-de-Araujo, Heloisa S.; Pontes, Carmen L. S.; Montenegro, Cyntia F.; Martin, Ana Carolina B. M.

    2010-01-01

    Cell migration is a key process for the defense of pluricellular organisms against pathogens, and it involves a set of surface receptors acting in an ordered fashion to contribute directionality to the movement. Among these receptors are the integrins, which connect the cell cytoskeleton to the extracellular matrix components, thus playing a central role in cell migration. Integrin clustering at focal adhesions drives actin polymerization along the cell leading edge, resulting in polarity of cell movement. Therefore, small integrin-binding proteins such as the snake venom disintegrins that inhibit integrin-mediated cell adhesion are expected to inhibit cell migration. Here we review the current knowledge on disintegrin and disintegrin-like protein effects on cell migration and their potential use as pharmacological tools in anti-inflammatory therapy as well as in inhibition of metastatic invasion. PMID:22069567

  9. Fish Rhabdoviruses

    USGS Publications Warehouse

    Kurath, G.; Winton, J.

    2008-01-01

    Many important viral pathogens of fish are members of the family Rhabdoviridae. The viruses in this large group cause significant losses in populations of wild fish as well as among fish reared in aquaculture. Fish rhabdoviruses often have a wide host and geographic range, and infect aquatic animals in both freshwater and seawater. The fish rhabdoviruses comprise a diverse collection of isolates that can be placed in one of two quite different groups: isolates that are members of the established genusNovirhabdovirus, and those that are most similar to members of the genus Vesiculovirus. Because the diseases caused by fish rhabdoviruses are important to aquaculture, diagnostic methods for their detection and identification are well established. In addition to regulations designed to reduce the spread of fish viruses, a significant body of research has addressed methods for the control or prevention of diseases caused by fish rhabdoviruses, including vaccination. The number of reported fish rhabdoviruses continues to grow as a result of the expansion of aquaculture, the increase in global trade, the development of improved diagnostic methods, and heightened surveillance activities. Fish rhabdoviruses serve as useful components of model systems to study vertebrate virus disease, epidemiology, and immunology.

  10. Insecticidal toxins from black widow spider venom

    PubMed Central

    Rohou, A.; Nield, J.; Ushkaryov, Y.A.

    2007-01-01

    The biological effects of Latrodectus spider venom are similar in animals from different phyla, but these symptoms are caused by distinct phylum-specific neurotoxins (collectively called latrotoxins) with molecular masses ranging from 110 to 140 kDa. To date, the venom has been found to contain five insecticidal toxins, termed α, β, γ, δ and ε-latroinsectotoxins (LITs). There is also a vertebrate-specific neurotoxin, α-latrotoxin (α-LTX), and one toxin affecting crustaceans, α-latrocrustatoxin (α-LCT). These toxins stimulate massive release of neurotransmitters from nerve terminals and act (1) by binding to specific receptors, some of which mediate an exocytotic signal, and (2) by inserting themselves into the membrane and forming ion-permeable pores. Specific receptors for LITs have yet to be identified, but all three classes of vertebrate receptors known to bind α-LTX are also present in insects. All LTXs whose structures have been elucidated (α-LIT, δ-LIT, α-LTX and α-LCT) are highly homologous and have a similar domain architecture, which consists of a unique N-terminal sequence and a large domain composed of 13–22 ankyrin repeats. Three-dimensional (3D) structure analysis, so far done for α-LTX only, has revealed its dimeric nature and an ability to form symmetrical tetramers, a feature probably common to all LTXs. Only tetramers have been observed to insert into membranes and form pores. A preliminary 3D reconstruction of a δ-LIT monomer demonstrates the spatial similarity of this toxin to the monomer of α-LTX. PMID:17210168

  11. Molecular cloning of a hyaluronidase from Bothrops pauloensis venom gland

    PubMed Central

    2014-01-01

    Background Hyaluronate is one of the major components of extracellular matrix from vertebrates whose breakdown is catalyzed by the enzyme hyaluronidase. These enzymes are widely described in snake venoms, in which they facilitate the spreading of the main toxins in the victim’s body during the envenoming. Snake venoms also present some variants (hyaluronidases-like substances) that are probably originated by alternative splicing, even though their relevance in envenomation is still under investigation. Hyaluronidases-like proteins have not yet been purified from any snake venom, but the cDNA that encodes these toxins was already identified in snake venom glands by transcriptomic analysis. Herein, we report the cloning and in silico analysis of the first hyaluronidase-like proteins from a Brazilian snake venom. Methods The cDNA sequence of hyaluronidase was cloned from the transcriptome of Bothrops pauloensis venom glands. This sequence was submitted to multiple alignment with other related sequences by ClustalW. A phylogenetic analysis was performed using MEGA 4 software by the neighbor joining (NJ) method. Results The cDNA from Bothrops pauloensis venom gland that corresponds to hyaluronidase comprises 1175 bp and codifies a protein containing 194 amino acid residues. The sequence, denominated BpHyase, was identified as hyaluronidase-like since it shows high sequence identities (above 83%) with other described snake venom hyaluronidase-like sequences. Hyaluronidases-like proteins are thought to be products of alternative splicing implicated in deletions of central amino acids, including the catalytic residues. Structure-based sequence alignment of BpHyase to human hyaluronidase hHyal-1 demonstrates a loss of some key secondary structures. The phylogenetic analysis indicates an independent evolution of BpHyal when compared to other hyaluronidases. However, these toxins might share a common ancestor, thus suggesting a broad hyaluronidase-like distribution among

  12. No evidence for proteolytic venom resistance in southern African ground squirrels.

    PubMed

    Phillips, Molly A; Waterman, Jane M; Du Plessis, Pg; Smit, Martin; Bennett, Nigel C

    2012-10-01

    Many mammalian species that interact with venomous snakes show resistances to venoms. The family Sciuridae has several North American members that harass venomous snakes and show proteolytic resistances in their sera. We examined sera collected from an African ground squirrel (Xerus inauris) against two sympatric venomous snakes (Bitis arietans and Naja annulifera) and found no support for proteolytic resistance. Our results add to our understanding of the risks in predator defense within the family Sciuridae.

  13. A New Assay for the Detection of Loxosceles Species (Brown Recluse) Spider Venom

    PubMed Central

    Gomez, Hernan F.; Krywko, Diann M.; Stoecker, William V.

    2011-01-01

    Study objective Dermal lesions from unrelated arthropod species and medical causes appear similar to Loxosceles species (brown recluse spider) bites. This may result in delayed diagnosis and treatment. We developed a sensitive Loxosceles species venom enzyme-linked immunosorbent assay (ELISA) and characterized the specificity of the assay by evaluating antigenic cross-reactivity from a variety of North American arthropod venoms. Methods North American arthropod (14 spiders, 2 scorpions, and 1 bee) venoms were studied. Three venom amounts (diluted in 100 μL of ELISA buffer) were assayed: 16,000 ng, 2,000 ng, and 40 ng. The latter quantity was selected because this is the observed maximum amount of venom we detect when inoculating dermis with amounts likely to be deposited by a spider bite. The larger venom amounts are overwhelming quantities designed to test the limits of the assay for arthropod venom cross-reactivity. Similar amounts of Loxosceles species venom and bovine albumin served as positive and negative controls, respectively. Results At the lowest amount of venom tested (40 ng), the ELISA detected only the Loxosceles species positive control. When 2,000 ng was assayed, only Scytodes fusca and Kukulcania hibernalis arachnid venoms (in addition to Loxosceles species) cross-reacted to the assay. Finally, at 16,000 ng, the ELISA assay modestly detected Diguetia canities, Heteropoda venatoria, Tegenaria agrestis, Plectreurys tristes, Dolomedes tenebrosus, and Hadrurus arizonensis arachnid venoms. Conclusion Cross-reactivity was observed in 8 of 17 North American arthropod venoms when large venom amounts were assayed with a Loxosceles species ELISA. By using a relevant quantity of venom, 40 ng, the assay was specific for Loxosceles species venom. The venom specificity of the ELISA may allow clinical application in Loxosceles species endemic regions of North America. PMID:11973553

  14. Comparison of the effect of Crotalus simus and Crotalus durissus ruruima venoms on the equine antibody response towards Bothrops asper venom: implications for the production of polyspecific snake antivenoms.

    PubMed

    Dos-Santos, Maria Cristina; Arroyo, Cynthia; Solano, Sergio; Herrera, María; Villalta, Mauren; Segura, Alvaro; Estrada, Ricardo; Gutiérrez, José María; León, Guillermo

    2011-02-01

    Antivenoms are preparations of immunoglobulins purified from the plasma of animals immunized with snake venoms. Depending on the number of venoms used during the immunization, antivenoms can be monospecific (if venom from a single species is used) or polyspecific (if venoms from several species are used). In turn, polyspecific antivenoms can be prepared by purifying antibodies from the plasma of animals immunized with a mixture of venoms, or by mixing antibodies purified from the plasma of animals immunized separately with single venom. The suitability of these strategies to produce polyspecific antibothropic-crotalic antivenoms was assessed using as models the venoms of Bothrops asper, Crotalus simus and Crotalus durissus ruruima. It was demonstrated that, when used as co-immunogen, C. simus and C. durissus ruruima venoms exert a deleterious effect on the antibody response towards different components of B. asper venom and in the neutralization of hemorrhagic and coagulant effect of this venom when compared with a monospecific B. asper antivenom. Polyspecific antivenoms produced by purifying immunoglobulins from the plasma of animals immunized with venom mixtures showed higher antibody titers and neutralizing capacity than those produced by mixing antibodies purified from the plasma of animals immunized separately with single venom. Thus, despite the deleterious effect of Crotalus sp venoms on the immune response against B. asper venom, the use of venom mixtures is more effective than the immunization with separate venoms for the preparation of polyspecific bothropic-crotalic antivenoms. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Differential Properties of Venom Peptides and Proteins in Solitary vs. Social Hunting Wasps

    PubMed Central

    Lee, Si Hyeock; Baek, Ji Hyeong; Yoon, Kyungjae Andrew

    2016-01-01

    The primary functions of venoms from solitary and social wasps are different. Whereas most solitary wasps sting their prey to paralyze and preserve it, without killing, as the provisions for their progeny, social wasps usually sting to defend their colonies from vertebrate predators. Such distinctive venom properties of solitary and social wasps suggest that the main venom components are likely to be different depending on the wasps’ sociality. The present paper reviews venom components and properties of the Aculeata hunting wasps, with a particular emphasis on the comparative aspects of venom compositions and properties between solitary and social wasps. Common components in both solitary and social wasp venoms include hyaluronidase, phospholipase A2, metalloendopeptidase, etc. Although it has been expected that more diverse bioactive components with the functions of prey inactivation and physiology manipulation are present in solitary wasps, available studies on venom compositions of solitary wasps are simply too scarce to generalize this notion. Nevertheless, some neurotoxic peptides (e.g., pompilidotoxin and dendrotoxin-like peptide) and proteins (e.g., insulin-like peptide binding protein) appear to be specific to solitary wasp venom. In contrast, several proteins, such as venom allergen 5 protein, venom acid phosphatase, and various phospholipases, appear to be relatively more specific to social wasp venom. Finally, putative functions of main venom components and their application are also discussed. PMID:26805885

  16. Differential Properties of Venom Peptides and Proteins in Solitary vs. Social Hunting Wasps.

    PubMed

    Lee, Si Hyeock; Baek, Ji Hyeong; Yoon, Kyungjae Andrew

    2016-01-22

    The primary functions of venoms from solitary and social wasps are different. Whereas most solitary wasps sting their prey to paralyze and preserve it, without killing, as the provisions for their progeny, social wasps usually sting to defend their colonies from vertebrate predators. Such distinctive venom properties of solitary and social wasps suggest that the main venom components are likely to be different depending on the wasps' sociality. The present paper reviews venom components and properties of the Aculeata hunting wasps, with a particular emphasis on the comparative aspects of venom compositions and properties between solitary and social wasps. Common components in both solitary and social wasp venoms include hyaluronidase, phospholipase A2, metalloendopeptidase, etc. Although it has been expected that more diverse bioactive components with the functions of prey inactivation and physiology manipulation are present in solitary wasps, available studies on venom compositions of solitary wasps are simply too scarce to generalize this notion. Nevertheless, some neurotoxic peptides (e.g., pompilidotoxin and dendrotoxin-like peptide) and proteins (e.g., insulin-like peptide binding protein) appear to be specific to solitary wasp venom. In contrast, several proteins, such as venom allergen 5 protein, venom acid phosphatase, and various phospholipases, appear to be relatively more specific to social wasp venom. Finally, putative functions of main venom components and their application are also discussed.

  17. Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms.

    PubMed

    Casewell, Nicholas R; Wagstaff, Simon C; Wüster, Wolfgang; Cook, Darren A N; Bolton, Fiona M S; King, Sarah I; Pla, Davinia; Sanz, Libia; Calvete, Juan J; Harrison, Robert A

    2014-06-24

    Variation in venom composition is a ubiquitous phenomenon in snakes and occurs both interspecifically and intraspecifically. Venom variation can have severe outcomes for snakebite victims by rendering the specific antibodies found in antivenoms ineffective against heterologous toxins found in different venoms. The rapid evolutionary expansion of different toxin-encoding gene families in different snake lineages is widely perceived as the main cause of venom variation. However, this view is simplistic and disregards the understudied influence that processes acting on gene transcription and translation may have on the production of the venom proteome. Here, we assess the venom composition of six related viperid snakes and compare interspecific changes in the number of toxin genes, their transcription in the venom gland, and their translation into proteins secreted in venom. Our results reveal that multiple levels of regulation are responsible for generating variation in venom composition between related snake species. We demonstrate that differential levels of toxin transcription, translation, and their posttranslational modification have a substantial impact upon the resulting venom protein mixture. Notably, these processes act to varying extents on different toxin paralogs found in different snakes and are therefore likely to be as important as ancestral gene duplication events for generating compositionally distinct venom proteomes. Our results suggest that these processes may also contribute to altering the toxicity of snake venoms, and we demonstrate how this variability can undermine the treatment of a neglected tropical disease, snakebite.

  18. Intraspecific Variation of Centruroides Edwardsii Venom from Two Regions of Colombia

    PubMed Central

    Estrada-Gómez, Sebastián; Cupitra, Nelson Ivan; Arango, Walter Murillo; Vargas Muñoz, Leidy Johana

    2014-01-01

    We report the first description studies, partial characterization, and intraspecific difference of Centruroides edwardsii, Gervais 1843, venom. C. edwardsii from two Colombian regions (Antioquia and Tolima) were evaluated. Both venoms showed hemolytic activity, possibly dependent of enzymatic active phospholipases, and neither coagulant nor proteolytic activities were observed. Venom electrophoretic profile showed significant differences between C. edwardsii venom from both regions. A high concentration of proteins with molecular masses between 31 kDa and 97.4 kDa, and an important concentration close or below 14.4 kDa were detected. RP-HPLC retention times between 38.2 min and 42.1 min, showed bands close to 14.4 kDa, which may correspond to phospholipases. RP-HPLC venom profile showed a well conserved region in both venoms between 7 and 17 min, after this, significant differences were detected. From Tolima region venom, 50 well-defined peaks were detected, while in the Antioquia region venom, 55 well-defined peaks were detected. Larvicidal activity was only detected in the C. edwardsii venom from Antioquia. No antimicrobial activity was observed using complete venom or RP-HPLC collected fractions of both venoms. Lethally activity (carried out on female albino swiss mice) was detected at doses over 19.2 mg/kg of crude venom. Toxic effects included distress, excitability, eye irritation and secretions, hyperventilation, ataxia, paralysis, and salivation. PMID:25025710

  19. Extremely low nerve growth facior (NGF) activity of sea snake (Hydrophiidae) venoms.

    PubMed

    Mariam, Khafizova; Tu, Anthony T

    2002-12-01

    Sea snake venoms contain less protein than those of land snakes (Toom et al., 1969). Sea snake venoms lack arginine ester hydrolyzing activity, whereas those of Crotalidae and Viperidae have such activity (Tu et al., 1966). Sea snakes live in salty water, and their venoms may be different from those of land snakes. Because of the difficulty in obtaining sea snake venoms, information about sea snake venoms is quite incomplete. NGF is commonly present in the venoms of land snakes such as Elapidae, Viperidae, and Crotalidae (Cohen and Levi-Montalcini, 1956; Lipps, 2002). It is therefore of interest to investigate the presence or absence of NGF in sea snake venoms. In order to investigate the presence or absence of NGF, five sea snake venoms were selected. Lapemis hardwickii (Hardwick's sea snake) and Acalyptophis peronii venom were obtained from the Gulf of Thailand. Hydrophis cyanocinctus (common sea snake) and Enhydrina schistosa (beaked sea snake) venom were obtained from the Strait of Malacca. Laticauda semifasciata (broad band blue sea snake) venom was also examined and the venom was obtained from Gato Island in the Philippines.

  20. Morphology and ultrastructure of the venom apparatus in the endoparasitic wasp Pteromalus puparum (Hymenoptera: Pteromalidae).

    PubMed

    Zhu, Jia-Ying; Ye, Gong-Yin; Hu, Cui

    2008-10-01

    The venom apparatus of the endoparasitic wasp Pteromalus puparum (Hymenoptera: Pteromalidae) was studied with light and electron microscope and was subjected to the electrophoretic and immunohistochemical analyses. Typically its venom apparatus consists of an unbranched venom gland and a venom reservoir, which is associated with a Dufour gland. The venom gland is lined by a series of secretory units. Each secretory unit comprises a secretory cell and a duct cell. The secretory cell is associated with an end apparatus to collect its secretions into the gland lumen. Secretory cells in the venom gland are characterized by extensive rough endoplasmic reticulum and numerous electron-dense vesicles in the distal and middle parts. They also exhibit several secretory granules and vacuoles. The venom reservoir presents three distinct regions: an external layer, composed by numerous fine muscle fibers; an internal layer, represented by epithelial cell with large nucleus; and an intima portion, represented by thin and uniform organization. The morphological aspect of numerous well-developed organelles responsible for protein generation observed is in agreement with the electrophoretic and immunohistochemical results which reveal that the rich proteinaceous components are present in the venom gland and venom reservoir. The venom proteins are first mainly produced in the secretory unit of venom gland, then drained to the lumen through the end apparatus, and are finally collected and stored in the venom reservoir.

  1. Partial purification of Chironex fleckeri (sea wasp) venom by immunochromatography with antivenom.

    PubMed

    Calton, G J; Burnett, J W

    1986-01-01

    Chironex fleckeri crude venom was partially purified using immobilized commercially available ovoid antivenom. The antibody preparation reacted with lethal, hemolytic, dermonecrotic and mouse writhing (pain) factors in the crude venom. The lethal activity was purified five fold, while the specific eluate contained lower quantities of hemolytic, dermonecrotic and mouse writhing activities than did the crude venom.

  2. Intraspecific variation of centruroides edwardsii venom from two regions of Colombia.

    PubMed

    Estrada-Gómez, Sebastián; Cupitra, Nelson Ivan; Arango, Walter Murillo; Muñoz, Leidy Johana Vargas

    2014-07-14

    We report the first description studies, partial characterization, and intraspecific difference of Centruroides edwardsii, Gervais 1843, venom. C. edwardsii from two Colombian regions (Antioquia and Tolima) were evaluated. Both venoms showed hemolytic activity, possibly dependent of enzymatic active phospholipases, and neither coagulant nor proteolytic activities were observed. Venom electrophoretic profile showed significant differences between C. edwardsii venom from both regions. A high concentration of proteins with molecular masses between 31 kDa and 97.4 kDa, and an important concentration close or below 14.4 kDa were detected. RP-HPLC retention times between 38.2 min and 42.1 min, showed bands close to 14.4 kDa, which may correspond to phospholipases. RP-HPLC venom profile showed a well conserved region in both venoms between 7 and 17 min, after this, significant differences were detected. From Tolima region venom, 50 well-defined peaks were detected, while in the Antioquia region venom, 55 well-defined peaks were detected. Larvicidal activity was only detected in the C. edwardsii venom from Antioquia. No antimicrobial activity was observed using complete venom or RP-HPLC collected fractions of both venoms. Lethally activity (carried out on female albino swiss mice) was detected at doses over 19.2 mg/kg of crude venom. Toxic effects included distress, excitability, eye irritation and secretions, hyperventilation, ataxia, paralysis, and salivation.

  3. Circus Venomous: an interactive tool for toxinology education.

    PubMed

    Vohra, Rais; Spano, Susanne

    2013-07-01

    Clinical education about envenomations and their treatment may convey clinical and zoological details inadequately or flatly. In recent years, the widespread availability of models and videos of venomous species have created unique opportunities for toxinology education. We share our experiences using a new toolkit for educating a diverse array of clinicians, students, and wilderness medicine enthusiasts. We examined the cost, number of participants, and satisfaction data since the initiation of a portable workshop featuring high-fidelity exhibits of venomous species. Termed the "Circus Venomous," this educational toolkit consists of several boxes of props, such as plastic models, photos, and preserved specimens of injurious species. The workshop consists of three phases: 1.) participants view all exhibits and answer clinical questions regarding venomous injuries; 2.) short video clips from television, internet, and cinema are viewed together, and myths about envenomation injuries are debunked; 3.) debriefing session and wrap-up. We have utilized the Circus Venomous to teach medical students, residents, practicing community clinicians, nurses, PAs, national and regional parkmedics, and wilderness enthusiasts. The major cost (about $800) was spent on the purchase of highly durable, lifelike models and well preserved real reptile and arachnid specimens. When formal feedback was solicited, the participants expressed high levels of satisfaction, scoring an average of 4.3, 4.4, and 4.3 out of 5 points in the respective areas of content, presentation, and practical value of the activity. Since we have used this exhibit with approximately 250 participants over 2 years, we estimate the materials cost per participant is approximately $3. The Circus Venomous is a novel, interactive, flexible, and cost-effective teaching tool about envenomation emergencies. We hope that this concept will encourage other clinical educators toward further innovation. Future directions for our

  4. Peptide fingerprinting of snake venoms by direct infusion nano-electrospray ionization mass spectrometry: potential use in venom identification and taxonomy.

    PubMed

    Souza, Gustavo H M F; Catharino, Rodrigo R; Ifa, Demian R; Eberlin, Marcos N; Hyslop, Stephen

    2008-05-01

    Fingerprinting by mass spectrometry has been increasingly used to study venom variations and for taxonomic analyses based on venom components. Most of these studies have concentrated on components heavier than 3 kDa, but Bothrops snake venoms contain many biologically active peptides, principally C-type natriuretic peptides and bradykinin-potentiating peptides (BPPs). In this work, we have examined the peptide profile of Bothrops venoms (B. alternatus, B. erythromelas, B. insularis, B. jararaca, B. jararacussu, B. leucurus and B. moojeni) using direct infusion nano-electrospray ionization mass spectrometry (nano-ESI-MS) subjecting the data further to principal components analysis (PCA) to assess whether the peptide distributions are reliable in distinguishing the venoms. ESI-MS of a low molar mass fraction obtained by ultrafiltration of each venom (5 kDa nominal cutoff filters) revealed that the venoms have a variety of peptides in common but that each venom also contains taxonomic marker peptides not shared with other venoms. One BPP peptide, QGGWPRPGPEIPP, was found to be common to the seven Bothrops species examined. This peptide may represent a specific marker for this genus since it was not found in the venom of the South American rattlesnake, Crotalus durissus terrificus. PCA on the ESI-MS data reveals a close relationship between B. jararaca, B. jararacussu and B. moojeni venoms, with B. leucurus and B. erythromelas being more distant from these three; B. alternatus and B. insularis were also located distant from these five species, as was C. d. terrificus. These results agree partially with established phylogenetic relationships among these species and suggest that ESI-MS peptide fingerprinting of snake venoms coupled with PCA is a useful tool for identifying venoms and for taxonomic analyses.

  5. Intraspecies variation in the venom of the rattlesnake Crotalus simus from Mexico: different expression of crotoxin results in highly variable toxicity in the venoms of three subspecies.

    PubMed

    Castro, Edgar Neri; Lomonte, Bruno; del Carmen Gutiérrez, María; Alagón, Alejandro; Gutiérrez, José María

    2013-07-11

    The composition and toxicological profile of the venom of the rattlesnake Crotalus simus in Mexico was analyzed at the subspecies and individual levels. Venoms of the subspecies C. s. simus, C. s. culminatus and C. s. tzabcan greatly differ in the expression of the heterodimeric neurotoxin complex 'crotoxin', with highest concentrations in C. s. simus, followed by C. s. tzabcan, whereas the venom of C. s. culminatus is almost devoid of this neurotoxic PLA2. This explains the large variation in lethality (highest in C. s. simus, which also exerts higher myotoxicity). Coagulant activity on plasma and fibrinogen occurs with the venoms of C. s. simus and C. s. tzabcan, being absent in C. s. culminatus which, in turn, presents higher crotamine-like activity. Proteomic analysis closely correlates with toxicological profiles, since the venom of C. s. simus has high amounts of crotoxin and of serine proteinases, whereas the venom of C. s. culminatus presents higher amounts of metalloproteinases and crotamine. This complex pattern of intraspecies venom variation provides valuable information for the diagnosis and clinical management of envenoming by this species in Mexico, as well as for the preparation of venom pools for the production and quality control of antivenoms. This study describes the variation in venom composition and activities of the three subspecies of Crotalus simus from Mexico. Results demonstrate that there is a notorious difference in these venoms, particularly regarding the content of the potent neurotoxic phospholipase A2 complex 'crotoxin'. In addition, other differences were observed regarding myotoxic and coagulant activities, and expression of the myotoxin 'crotamine'. These findings have implications in, at least, three levels: (a) the adaptive role of variations in venom composition; (b) the possible differences in the clinical manifestations of envenomings by these subspecies in Mexico; and (c) the design of venom mixtures for the preparation of

  6. Venom immunotherapy improves health-related quality of life in patients allergic to yellow jacket venom.

    PubMed

    Oude Elberink, Joanne N G; De Monchy, Jan G R; Van Der Heide, Sicco; Guyatt, Gordon H; Dubois, Anthony E J

    2002-07-01

    Venom immunotherapy (VIT) is effective in preventing anaphylactic reactions after insect stings. The effect of VIT on health-related quality of life (HRQL) was studied to evaluate whether this treatment is of importance to patients. We compared HRQL outcomes measured with a disease-specific instrument (Vespid Allergy Quality-of-Life Questionnaire [VQLQ]) in patients allergic to yellow jacket venom treated with VIT or with an adrenalin self-administration device (EpiPen) in an open-label, randomized, controlled trial. Consenting patients were block randomized to either VIT or EpiPen. Patients received uniform, standardized information, which specified the risk of their condition and the risks and benefits of both treatment options. HRQL measures took place before and after 1 year of treatment with VIT or EpiPen. Seventy-four patients agreed to be randomized, of whom 36 received VIT and 38 an EpiPen. The mean change in VQLQ score in the group randomized to VIT was 1.07 (95% CI, 0.68-1.46), and this improvement was statistically significant (P <.0001) compared with that seen in the group randomized to the EpiPen, in which this change was -0.43 (95% CI, -0.71 to -0.16). These differences were seen in both men and women, persons with more or less general anxiety, and those stung recently and those stung more than a year before their outpatient department visit. The overall proportion of patients receiving benefit from VIT is 0.72, generating a number needed to treat of 1.4. VIT results in a clinically important improvement in HRQL in patients allergic to yellow jacket venom in all subgroups studied. Of every 3 patients treated with VIT, 2 patients experience an important improvement in their quality of life.

  7. Honeybee venom proteome profile of queens and winter bees as determined by a mass spectrometric approach.

    PubMed

    Danneels, Ellen L; Van Vaerenbergh, Matthias; Debyser, Griet; Devreese, Bart; de Graaf, Dirk C

    2015-10-30

    Venoms of invertebrates contain an enormous diversity of proteins, peptides, and other classes of substances. Insect venoms are characterized by a large interspecific variation resulting in extended lists of venom compounds. The venom composition of several hymenopterans also shows different intraspecific variation. For instance, venom from different honeybee castes, more specifically queens and workers, shows quantitative and qualitative variation, while the environment, like seasonal changes, also proves to be an important factor. The present study aimed at an in-depth analysis of the intraspecific variation in the honeybee venom proteome. In summer workers, the recent list of venom proteins resulted from merging combinatorial peptide ligand library sample pretreatment and targeted tandem mass spectrometry realized with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS/MS). Now, the same technique was used to determine the venom proteome of queens and winter bees, enabling us to compare it with that of summer bees. In total, 34 putative venom toxins were found, of which two were never described in honeybee venoms before. Venom from winter workers did not contain toxins that were not present in queens or summer workers, while winter worker venom lacked the allergen Api m 12, also known as vitellogenin. Venom from queen bees, on the other hand, was lacking six of the 34 venom toxins compared to worker bees, while it contained two new venom toxins, in particularly serine proteinase stubble and antithrombin-III. Although people are hardly stung by honeybees during winter or by queen bees, these newly identified toxins should be taken into account in the characterization of a putative allergic response against Apis mellifera stings.

  8. Honeybee Venom Proteome Profile of Queens and Winter Bees as Determined by a Mass Spectrometric Approach

    PubMed Central

    Danneels, Ellen L.; Van Vaerenbergh, Matthias; Debyser, Griet; Devreese, Bart; de Graaf, Dirk C.

    2015-01-01

    Venoms of invertebrates contain an enormous diversity of proteins, peptides, and other classes of substances. Insect venoms are characterized by a large interspecific variation resulting in extended lists of venom compounds. The venom composition of several hymenopterans also shows different intraspecific variation. For instance, venom from different honeybee castes, more specifically queens and workers, shows quantitative and qualitative variation, while the environment, like seasonal changes, also proves to be an important factor. The present study aimed at an in-depth analysis of the intraspecific variation in the honeybee venom proteome. In summer workers, the recent list of venom proteins resulted from merging combinatorial peptide ligand library sample pretreatment and targeted tandem mass spectrometry realized with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS/MS). Now, the same technique was used to determine the venom proteome of queens and winter bees, enabling us to compare it with that of summer bees. In total, 34 putative venom toxins were found, of which two were never described in honeybee venoms before. Venom from winter workers did not contain toxins that were not present in queens or summer workers, while winter worker venom lacked the allergen Api m 12, also known as vitellogenin. Venom from queen bees, on the other hand, was lacking six of the 34 venom toxins compared to worker bees, while it contained two new venom toxins, in particularly serine proteinase stubble and antithrombin-III. Although people are hardly stung by honeybees during winter or by queen bees, these newly identified toxins should be taken into account in the characterization of a putative allergic response against Apis mellifera stings. PMID:26529016

  9. Evolutionary trends in venom composition in the western rattlesnakes (Crotalus viridis sensu lato): toxicity vs. tenderizers.

    PubMed

    Mackessy, Stephen P

    2010-07-01

    The Western Rattlesnake (Crotalus viridis sensu lato, now including Crotalus oreganus) is broadly distributed across the western half of the United States, northwestern Mexico and southwestern Canada, and eight subspecies are currently recognized. Although some venom characteristics have been noted for most subspecies, a systematic study of venoms from all subspecies has not been reported. Venom was extracted from snakes collected from approximate geographic range centers for all subspecies and analyzed using SDS-PAGE, MALDI-TOF mass spectrometry, enzyme and toxicity assays. Electrophoretic and mass spectrometric analyses demonstrated that small myotoxins, disintegrins and PLA(2) were abundant in most venoms. PIII and PI metalloproteinases ( approximately 54 kDa and 23 kDa, respectively) were common to all venoms except C. o. concolor, C. o. caliginis and C.o. helleri. Metalloproteinase activity was highest in C. o. cerberus and lowest in C. o. concolor venoms ( approximately 100-fold difference). Conversely, C. o. concolor venom was the most toxic and C. o. cerberus venom was least toxic (15-fold difference). In general, venoms with high metalloproteinase activity were less toxic (type I venoms), while venoms which were highly toxic showed low protease activity (type II venoms). Within the C. viridis/oreganus complex, these two extremes of venom compositional phenotypes are observed, and it appears that high metalloproteinase activity and high toxicity are incompatible qualities of these venoms. The functional significance of these biochemical characteristics likely relates to characteristics of prey consumed, and venoms with low metalloproteinase activity may constrain snake prey selection or foraging activity patterns.

  10. Proteomic characterization and comparison of Malaysian Bungarus candidus and Bungarus fasciatus venoms.

    PubMed

    Rusmili, Muhamad Rusdi Ahmad; Yee, Tee Ting; Mustafa, Mohd Rais; Hodgson, Wayne C; Othman, Iekhsan

    2014-10-14

    Kraits (Bungarus spp.) are highly venomous elapids that are only found in Asia. In the current study, 103 and 86 different proteins were identified from Bungarus candidus and Bungarus fasciatus venoms, respectively. These proteins were classified into 18 different venom protein families. Both venoms were found to contain a high percentage of three finger toxins, phospholipase A2 enzymes and Kunitz-type inhibitors. Smaller number of high molecular weight enzymes such as L-amino acid oxidase, hyaluronidases, and acetylcholinesterase were also detected in the venoms. We also detected some unique proteins that were not known to be present in these venoms. The presence of a natriuretic peptide, vespryn, and serine protease families was detected in B. candidus venom. We also detected the presence of subunit A and B of β-bungarotoxin and α-bungarotoxin which had not been previously found in B. fasciatus venom. Understanding the proteome composition of Malaysian krait species will provide useful information on unique toxins and proteins which are present in the venoms. This knowledge will assist in the management of krait envenoming. In addition, these proteins may have potential use as research tools or as drug-design templates. This study has revealed the proteome composition of Malaysian B. candidus and B. fasciatus venoms, two medically important snake species in Asia. Information on the venom proteome of these species will provide useful information for krait bite management and aid in antivenom selection. Venom proteome profiles of these venoms showed that there are significant differences in the venom protein family compositions. Detection of proteins and peptides that have not been documented in these species such as natriuretic peptides, vespryn and serine proteases provides new knowledge on the composition of these venoms. The roles of these new proteins and peptides in krait envenoming are still unknown. Discovery of these proteins and peptides may also be

  11. Injuries caused by the venomous catfish pintado and cachara (Pseudoplatystoma genus) in fishermen of the Pantanal region in Brazil.

    PubMed

    Aquino, Giuliano N R DE; Souza, Celso C DE; Haddad, Vidal; Sabino, José

    2016-09-01

    the fishing activity throughout the Upper Paraguay River Basin has huge financial and biological importance. This retrospective study investigated the occurrence of injuries caused by fish of the Pseudoplatystoma genus (spotted catfish or pintado and striped catfish or cachara) in professional fishermen of the Pantanal of Mato Grosso do Sul State. we collected information through a questionnaire, showing that fishing is carried out by workers with low level of education, mainly adults or seniors with low financial gains. in Miranda town, 126 of 315 fishermen were interviewed and 38 individuals reported injuries (30.16%). In Corumbá town, 355 of 627 fishermen were interviewed, and 111 (56,61%) reported injuries. The lacerated lesions were the most common, associate with edema, erythema, radiating pain to the root of the limb, paresthesias and local necrosis. More rarely, they reported the occurrence of fever, cardiac arrhythmias and cold sweating. These manifestations may be associated with late secondary infections or envenomations caused by the toxins in the stingers of the fish. Many questionable and inappropriate treatments are used, sometimes aggravating the injuries. the freshwater professional fishermen need guidance on first aid measures and prevention of accidents caused by these venomous fish.

  12. Texture Fish

    ERIC Educational Resources Information Center

    Stone, Julie

    2007-01-01

    In an effort to provide an opportunity for her first graders to explore texture through an engaging subject, the author developed a three-part lesson that features fish in a mixed-media artwork: (1) Exploring Textured Paint; (2) Creating the Fish; and (3) Role Playing. In this lesson, students effectively explore texture through painting, drawing,…

  13. Texture Fish

    ERIC Educational Resources Information Center

    Stone, Julie

    2007-01-01

    In an effort to provide an opportunity for her first graders to explore texture through an engaging subject, the author developed a three-part lesson that features fish in a mixed-media artwork: (1) Exploring Textured Paint; (2) Creating the Fish; and (3) Role Playing. In this lesson, students effectively explore texture through painting, drawing,…

  14. Snake venomics of Crotalus tigris: the minimalist toxin arsenal of the deadliest Nearctic rattlesnake venom. Evolutionary Clues for generating a pan-specific antivenom against crotalid type II venoms [corrected].

    PubMed

    Calvete, Juan J; Pérez, Alicia; Lomonte, Bruno; Sánchez, Elda E; Sanz, Libia

    2012-02-03

    We report the proteomic and antivenomic characterization of Crotalus tigris venom. This venom exhibits the highest lethality for mice among rattlesnakes and the simplest toxin proteome reported to date. The venom proteome of C. tigris comprises 7-8 gene products from 6 toxin families; the presynaptic β-neurotoxic heterodimeric PLA(2), Mojave toxin, and two serine proteinases comprise, respectively, 66 and 27% of the C. tigris toxin arsenal, whereas a VEGF-like protein, a CRISP molecule, a medium-sized disintegrin, and 1-2 PIII-SVMPs each represent 0.1-5% of the total venom proteome. This toxin profile really explains the systemic neuro- and myotoxic effects observed in envenomated animals. In addition, we found that venom lethality of C. tigris and other North American rattlesnake type II venoms correlates with the concentration of Mojave toxin A-subunit, supporting the view that the neurotoxic venom phenotype of crotalid type II venoms may be described as a single-allele adaptation. Our data suggest that the evolutionary trend toward neurotoxicity, which has been also reported for the South American rattlesnakes, may have resulted by pedomorphism. The ability of an experimental antivenom to effectively immunodeplete proteins from the type II venoms of C. tigris, Crotalus horridus , Crotalus oreganus helleri, Crotalus scutulatus scutulatus, and Sistrurus catenatus catenatus indicated the feasibility of generating a pan-American anti-Crotalus type II antivenom, suggested by the identification of shared evolutionary trends among South and North American Crotalus species.

  15. Snake venomics and antivenomics of Bothrops atrox venoms from Colombia and the Amazon regions of Brazil, Perú and Ecuador suggest the occurrence of geographic variation of venom phenotype by a trend towards paedomorphism.

    PubMed

    Núñez, Vitelbina; Cid, Pedro; Sanz, Libia; De La Torre, Pilar; Angulo, Yamileth; Lomonte, Bruno; Gutiérrez, José María; Calvete, Juan J

    2009-11-02

    The venom proteomes of Bothrops atrox from Colombia, Brazil, Ecuador, and Perú were characterized using venomic and antivenomic strategies. Our results evidence the existence of two geographically differentiated venom phenotypes. The venom from Colombia comprises at least 26 different proteins belonging to 9 different groups of toxins. PI-metalloproteinases and K49-PLA(2) molecules represent the most abundant toxins. On the other hand, the venoms from Brazilian, Ecuadorian, and Peruvian B. atrox contain predominantly PIII-metalloproteinases. These toxin profiles correlate with the venom phenotypes of adult and juvenile B. asper from Costa Rica, respectively, suggesting that paedomorphism represented a selective trend during the trans-Amazonian southward expansion of B. atrox through the Andean Corridor. The high degree of crossreactivity of a Costa Rican polyvalent (Bothrops asper, Lachesis stenophrys, Crotalus simus) antivenom against B. atrox venoms further evidenced the close evolutionary kinship between B. asper and B. atrox. This antivenom was more efficient immunodepleting proteins from the venoms of B. atrox from Brazil, Ecuador, and Perú than from Colombia. Such behaviour may be rationalized taking into account the lower content of poorly immunogenic toxins, such as PLA(2) molecules and PI-SVMPs in the paedomorphic venoms. The immunological profile of the Costa Rican antivenom strongly suggests the possibility of using this antivenom for the management of snakebites by B. atrox in Colombia and the Amazon regions of Ecuador, Perú and Brazil.

  16. A Review and Database of Snake Venom Proteomes

    PubMed Central

    Tasoulis, Theo

    2017-01-01

    Advances in the last decade combining transcriptomics with established proteomics methods have made possible rapid identification and quantification of protein families in snake venoms. Although over 100 studies have been published, the value of this information is increased when it is collated, allowing rapid assimilation and evaluation of evolutionary trends, geographical variation, and possible medical implications. This review brings together all compositional studies of snake venom proteomes published in the last decade. Compositional studies were identified for 132 snake species: 42 from 360 (12%) Elapidae (elapids), 20 from 101 (20%) Viperinae (true vipers), 65 from 239 (27%) Crotalinae (pit vipers), and five species of non-front-fanged snakes. Approximately 90% of their total venom composition consisted of eight protein families for elapids, 11 protein families for viperines and ten protein families for crotalines. There were four dominant protein families: phospholipase A2s (the most common across all front-fanged snakes), metalloproteases, serine proteases and three-finger toxins. There were six secondary protein families: cysteine-rich secretory proteins, l-amino acid oxidases, kunitz peptides, C-type lectins/snaclecs, disintegrins and natriuretic peptides. Elapid venoms contained mostly three-finger toxins and phospholipase A2s and viper venoms metalloproteases, phospholipase A2s and serine proteases. Although 63 protein families were identified, more than half were present in <5% of snake species studied and always in low abundance. The importance of these minor component proteins remains unknown. PMID:28927001

  17. Sex-related clinical aspects in insect venom anaphylaxis.

    PubMed

    Nittner-Marszalska, Marita; Liebhart, Jerzy; Dor-Wojnarowska, Anna

    2015-06-01

    Experimental studies, epidemiological data, and clinical observations suggest that the gender factor is involved in the development and manifestation of IgE-dependent allergic diseases. We intend to answer the question if sex-related factors may play a role in Hymenoptera venom allergy (HVA). In the majority of recent studies the frequency of HVA symptoms with respect to both LL and SYS reactions is similar for men and women, while proven sensitization to insect venom is less frequent in women. Studies assessing clinical reactivity in HVA indicate that male sex and vespid venom allergy are factors increasing the risk of severe allergic reactions. Regarding the risk of adverse events associated with gender in the course of venom immunotherapy (VIT), the results of two large EAACI multicenter studies are discordant. In the first study, women showed increased risk of VIT adverse events. In the latter, systemic allergic side effects were not associated with gender. Despite theoretical premises and certain clinical observations indicating an important role of estrogens in allergic diseases, their influence on stinging insects' venom hypersensitivity is not unequivocal and remains still open. Further studies on the safety of VIT in females seem to be advisable. © The Author(s) 2015.

  18. A perspective on toxicology of Conus venom peptides.

    PubMed

    Kumar, Palanisamy Satheesh; Kumar, Dhanabalan Senthil; Umamaheswari, Sundaresan

    2015-05-01

    The evolutionarily unique and ecologically diverse family Conidae presents fundamental opportunities for marine pharmacology research and drug discovery. The focus of this investigation is to summarize the worldwide distribution of Conus and their species diversity with special reference to the Indian coast. In addition, this study will contribute to understanding the structural properties of conotoxin and therapeutic application of Conus venom peptides. Cone snails can inject a mix of various conotoxins and these venoms are their major weapon for prey capture, and may also have other biological purposes, and some of these conotoxins fatal to humans. Conus venoms contain a remarkable diversity of pharmacologically active small peptides; their targets are an iron channel and receptors in the neuromuscular system. Interspecific divergence is pronounced in venom peptide genes, which is generally attributed to their species specific biotic interactions. There is a notable interspecific divergence observed in venom peptide genes, which can be justified as of biotic interactions that stipulate species peculiar habitat and ecology of cone snails. There are several conopeptides used in clinical trials and one peptide (Ziconotide) has received FDA approval for treatment of pain. This perspective provides a comprehensive overview of the distribution of cone shells and focus on the molecular approach in documenting their taxonomy and diversity with special reference to geographic distribution of Indian cone snails, structure and properties of conopeptide and their pharmacological targets and future directions. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  19. [Understanding snake venoms: 50 years of research in Latin America].

    PubMed

    Gutiérrez, José María

    2002-06-01

    As a tribute to Revista de Biología Tropical in its 50th anniversary, this review describes some of the main research efforts carried out in the study of the chemical composition and the mechanism of action of toxins present in the venoms of snakes distributed in Latin America. Venom proteins involved in neurotoxicity, coagulopathies, hemorrhage and muscle necrosis are discussed, together with a description of the inflammatory reactions elicited by these venoms and toxins. In addition, the search for inhibitory substances present in plants and animals that may be utilized in the neutralization of venoms is analyzed. Some of the clinical studies performed on snakebite envenomations in Latin America are also reviewed, together with the development of technologies aimed at improving the quality of antivenoms produced in the region. Toxinology has become a fruitful and stimulating research field in Latin America which has contributed to a better understanding of snake venoms as well as to an improved management of snake bitten patients.

  20. Novel apigenin based small molecule that targets snake venom metalloproteases.

    PubMed

    Srinivasa, Venkatachalaiah; Sundaram, Mahalingam S; Anusha, Sebastian; Hemshekhar, Mahadevappa; Chandra Nayaka, Siddaiah; Kemparaju, Kempaiah; Basappa; Girish, Kesturu S; Rangappa, Kanchugarakoppal S

    2014-01-01

    The classical antivenom therapy has appreciably reduced snakebite mortality rate and thus is the only savior drug available. Unfortunately, it considerably fails to shield the viper bite complications like hemorrhage, local tissue degradation and necrosis responsible for severe morbidity. Moreover, the therapy is also tagged with limitations including anaphylaxis, serum sickness and poor availability. Over the last decade, snake venom metalloproteases (SVMPs) are reported to be the primary component responsible for hemorrhage and tissue degradation at bitten site. Thus, antivenom inability to offset viper venom-induced local toxicity has been a basis for an insistent search for SVMP inhibitors. Here we report the inhibitory effect of compound 5d, an apigenin based molecule against SVMPs both in silico and in vivo. Several apigenin analogues are synthesized using multicomponent Ugi reactions. Among them, compound 5d effectively abrogated Echis carinatus (EC) venom-induced local hemorrhage, tissue necrosis and myotoxicity in a dose dependant fashion. The histopathological study further conferred effective inhibition of basement membrane degradation, and accumulation of inflammatory leucocytes at the site of EC venom inoculation. The compound also protected EC venom-induced fibrin and fibrinogen degradation. The molecular docking of compound 5d and bothropasin demonstrated the direct interaction of hydroxyl group of compound with Glu146 present in hydrophobic pocket of active site and does not chelate Zn2+. Hence, it is concluded that compound 5d could be a potent agent in viper bite management.

  1. Novel Apigenin Based Small Molecule that Targets Snake Venom Metalloproteases

    PubMed Central

    Anusha, Sebastian; Hemshekhar, Mahadevappa; Chandra Nayaka, Siddaiah; Kemparaju, Kempaiah; Basappa; Girish, Kesturu S.; Rangappa, Kanchugarakoppal S.

    2014-01-01

    The classical antivenom therapy has appreciably reduced snakebite mortality rate and thus is the only savior drug available. Unfortunately, it considerably fails to shield the viper bite complications like hemorrhage, local tissue degradation and necrosis responsible for severe morbidity. Moreover, the therapy is also tagged with limitations including anaphylaxis, serum sickness and poor availability. Over the last decade, snake venom metalloproteases (SVMPs) are reported to be the primary component responsible for hemorrhage and tissue degradation at bitten site. Thus, antivenom inability to offset viper venom-induced local toxicity has been a basis for an insistent search for SVMP inhibitors. Here we report the i