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Sample records for agelenopsis aperta venom

  1. Molecular evidence for Pleistocene glacial cycles driving diversification of a North American desert spider, Agelenopsis aperta.

    PubMed

    Ayoub, Nadia A; Riechert, Susan E

    2004-11-01

    The influence of historical climatic vs. geological changes on species diversification patterns was investigated in a widely distributed North American desert spider, Agelenopsis aperta (Araneae: Agelenidae), with particular reference to Pleistocene glacial cycles and earlier patterns of mountain building. Levels of sequence divergence obtained from the mitochondrial gene, cytochrome oxidase I, dated to the Pleistocene, eliminating Rocky Mountain orogeny as a cause of diversification, as orogeny ended 4 million years ago. The results of phylogenetic and network analyses showed the presence of three geographically defined clades, which were consistent with the presence of at least three glacial refugia: (i) east of the Rocky Mountains; (ii) between the Rocky Mountains and Sierra Nevadas; and (iii) west of the Sierra Nevadas. In addition, populations within the Rocky Mountains exhibited significantly lower genetic diversity than populations east of the Rocky Mountains and the haplotypes found within the Rockies were a subset of eastern haplotypes. These patterns suggest that a post-Pleistocene range expansion occurred out of an eastern glacial refugium into the Rocky Mountains. Examination of phylogeographical studies of other North American desert taxa indicated that mountain building explained diversification patterns more effectively for some taxa but Pleistocene climate change was more important for others, including A. aperta.

  2. Proteomic analysis of amniotic fluid of pregnant rats with spina bifida aperta.

    PubMed

    Shan, Liping; Fan, Yang; Li, Hui; Liu, Wei; Gu, Hui; Zhou, Fenghua; Yuan, Zhengwei

    2012-02-02

    Congenital spina bifida aperta is a common congenital malformation in children and has an incidence of 1‰ to 5‰ in China. However, we currently lack specific biomarkers for screening or prenatal diagnosis and there is no method to entirely cure or prevent such defects. In this study, we used two-dimensional gel electrophoresis (2-DE)/mass spectrometry (MS) to characterize differentially expressed proteins in amniotic-fluid samples (AFSs) of embryonic day (E) 17.5 rat fetuses with spina bifida aperta induced by retinoic acid (RA). We identified five proteins differentially expressed in AFSs of spina bifida aperta, including three upregulated proteins (transferrin, alpha-1 antiproteinase and signal recognition particle receptor, B subunit [SRPRB] 55 kDa), two downregulated proteins (apolipoprotein A IV [APO A4] and Srprb 77 kDa). Specifically, we found 11 alpha-1 fetoprotein (AFP) fragments that were downregulated and 35 AFP fragments that were upregulated in AFSs from embryos with spina bifida aperta. Of the downregulated AFP fragments, 72.7% (8/11) were confined to the AFP N-terminus (amino acids [aas] 25-440) and 77.1% (27/35) of upregulated AFP fragments were confined to the AFP C-terminus (aas 340-596). We also confirmed APO A4 and AFP by immunoblot analysis. This is the first comparative proteomic study of AFSs from rat fetuses with spina bifida aperta. We demonstrate proteomic alterations in the AFS of spina bifida aperta, which may provide new insights in neural tube defects and contribute to the prenatal screening.

  3. A Population Growth Trend Analysis for Neotricula aperta, the Snail Intermediate Host of Schistosoma mekongi, after Construction of the Pak-Mun Dam

    PubMed Central

    Attwood, Stephen W.; Upatham, E. Suchart

    2013-01-01

    Background The Pak-Mun dam is a controversial hydro-power project on the Mun River in Northeast Thailand. The dam is sited in a habitat of the freshwater snail Neotricula aperta, which is the intermediate host for the parasitic blood-fluke Schistosoma mekongi causing Mekong schistosomiasis in humans in Cambodia and Laos. Few data are available which can be used to assess the effects of water resource development on N. aperta. The aim of this study was to obtain data and to analyze the possible impact of the dam on N. aperta population growth. Methodology/Principal Findings Estimated population densities were recorded for an N. aperta population in the Mun River 27 km upstream of Pak-Mun, from 1990 to 2011. The Pak-Mul dam began to operate in 1994. Population growth was modeled using a linear mixed model expression of a modified Gompertz stochastic state-space exponential growth model. The N. aperta population was found to be quite stable, with the estimated growth parameter not significantly different from zero. Nevertheless, some marked changes in snail population density were observed which were coincident with changes in dam operation policy. Conclusions/Significance The study found that there has been no marked increase in N. aperta population growth following operation of the Pak-Mun dam. The analysis did indicate a large and statistically significant increase in population density immediately after the dam came into operation; however, this increase was not persistent. The study has provided the first vital baseline data on N. aperta population behavior near to the Pak-Mun dam and suggests that the operation policy of the dam may have an impact on snail population density. Nevertheless, additional studies are required for other N. aperta populations in the Mun River and for an extended time series, to confirm or refine the findings of this work. PMID:24244775

  4. 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.

  5. 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

  6. Screening for Fetal Spina Bifida Aperta by the Ultrasound and Intracranial Translucency Examinations at 11-13(+6) Weeks of Gestation.

    PubMed

    Liu, Min; Liu, Ying; Li, Zhi-Hong; Yu, Ding

    2015-06-01

    The objective of the study is to evaluate the clinical significance of screening for fetal spina bifida aperta by ultrasound examination and intracranial translucency (IT) measurement at 11-13(+6) weeks of gestation. About 1,479 women at 11-13(+6) weeks of gestation in our hospital in 2012 were included as observation group, and 1,608 women at 11-13(+6) weeks of gestation without IT measurement in 2011 was included as controls. Detection rates of fetal spina bifida aperta in two groups were compared. The translucency thickness between the brain stem and choroid plexus and crown-rump length (CRL) in mid-sagittal view of the fetal face was measured, and translucency thickness and CRL in fetuses with spina bifida and healthy ones were compared. Detection rate of fetal spina bifida aperta in observation group was significantly higher than that in control group (six cases in observation group and one case in control group, p = 0.046). IT thickness was significantly lower in fetuses with spina bifida aperta (0.01 ± 1.25 mm) than that in healthy ones (1.73 ± 0.32 mm) (p < 0.001). There was positive correlation in healthy fetuses between IT thickness and CRL (r = 0.702, p < 0.001), but not in fetuses with spina bifida aperta (r = 0.001, p = 0.081). Ultrasound examination with IT measurement at 11-13(+6) weeks of gestation can be used to screen for fetal spina bifida aperta, and the reduction of IT thickness is an indicator of spina bifida aperta.

  7. Allergies to Insect Venom

    MedlinePlus

    Allergies To Insect Venom Facts About Allergies The tendency to develop allergies may be inherited. If you have allergic tendencies and ... lives of those who are sensitive to it...insect venom! Although less common than pollen allergy, insect ...

  8. Application potential of bone marrow mesenchymal stem cell (BMSCs) based tissue-engineering for spinal cord defect repair in rat fetuses with spina bifida aperta.

    PubMed

    Li, Xiaoshuai; Yuan, Zhengwei; Wei, Xiaowei; Li, Hui; Zhao, Guifeng; Miao, Jiaoning; Wu, Di; Liu, Bo; Cao, Songying; An, Dong; Ma, Wei; Zhang, Henan; Wang, Weilin; Wang, Qiushi; Gu, Hui

    2016-04-01

    Spina bifida aperta are complex congenital malformations resulting from failure of fusion in the spinal neural tube during embryogenesis. Despite surgical repair of the defect, most patients who survive with spina bifida aperta have a multiple system handicap due to neuron deficiency of the defective spinal cord. Tissue engineering has emerged as a novel treatment for replacement of lost tissue. This study evaluated the prenatal surgical approach of transplanting a chitosan-gelatin scaffold seeded with bone marrow mesenchymal stem cells (BMSCs) in the healing the defective spinal cord of rat fetuses with retinoic acid induced spina bifida aperta. Scaffold characterisation revealed the porous structure, organic and amorphous content. This biomaterial promoted the adhesion, spreading and in vitro viability of the BMSCs. After transplantation of the scaffold combined with BMSCs, the defective region of spinal cord in rat fetuses with spina bifida aperta at E20 decreased obviously under stereomicroscopy, and the skin defect almost closed in many fetuses. The transplanted BMSCs in chitosan-gelatin scaffold survived, grew and expressed markers of neural stem cells and neurons in the defective spinal cord. In addition, the biomaterial presented high biocompatibility and slow biodegradation in vivo. In conclusion, prenatal transplantation of the scaffold combined with BMSCs could treat spinal cord defect in fetuses with spina bifida aperta by the regeneration of neurons and repairmen of defective region.

  9. 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.

  10. Observations on Neotricula aperta (Gastropoda: Pomatiopsidae) population densities in Thailand and central Laos: implications for the spread of Mekong schistosomiasis

    PubMed Central

    2012-01-01

    Background The snail Neotricula aperta transmits Mekong schistosomiasis in southern Laos and Cambodia, with about 1.5 million people at risk of infection. Plans are under consideration for at least 12 hydroelectric power dams on the lower Mekong river and much controversy surrounds predictions of their environmental impacts. Unfortunately, there are almost no ecological data (such as long term population trend studies) available for N. aperta which could be used in impact assessment. Predictions currently assume that the impacts will be the same as those observed in Africa (i.e., a worsening of the schistosomiasis problem); however, marked ecological differences between the snails involved suggest that region specific models are required. The present study was performed as an initial step in providing data, which could be useful in the planning of water resource development in the Mekong. Snail population density records were analyzed for populations close to, and far downstream of, the Nam Theun 2 (NT2) project in Laos in order to detect any changes that might be attributable to impoundment. Results The population immediately downstream of NT2 and that sampled 400 km downstream in Thailand both showed a long term trend of slow growth from 1992 to 2005; however, both populations showed a marked decline in density between 2005 and 2011. The decline in Thailand was to a value significantly lower than that predicted by a linear mixed model for the data, whilst the population density close to NT2 fell to undetectable levels in 2011 from densities of over 5000 m-2 in 2005. The NT2 dam began operation in 2010. Conclusions The impact of the NT2 dam on N. aperta population density could be more complex than first thought and may reflect the strict ecological requirements of this snail. There was no indication that responses of N. aperta populations to dam construction are similar to those observed with Bulinus and Schistosoma haematobium in Africa, for example. In view

  11. [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.

  12. 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.

  13. 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.

  14. 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

  15. [Life history traits of the snail Helix aperta Born from Tunisia raised in a laboratory environment: influence of photoperiod].

    PubMed

    de Vaufleury, Annette; Gimbert, Frédéric

    2009-09-01

    The present work revealed that growth and reproduction of Helix aperta (syn. Cantareus apertus), sampled at the end of summer in the region of Bazina (Tunisia), are stimulated by short-day photoperiod (SD 8hL-16hD) and inhibited by long-day photoperiod (LD 18hL-6hD). Indeed, under SD at 20 degrees C, 80% humidity and ad libitum Helixal snail food, 2 generations (F1, F2) were obtained in 10 months with no refractory period. The effects of photoperiod on growth were found to be reversible and appeared after a time lag of 4 and 8 weeks for stimulation by SD and the inhibition by LD respectively.

  16. 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

  17. 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.

  18. Regioselective solid-phase synthesis of N-mono-hydroxylated and N-mono-methylated acylpolyamine spider toxins using an 2-(ortho-nitrophenyl)ethanal-modified resin.

    PubMed

    Pauli, Denise; Bienz, Stefan

    2015-04-21

    A recently introduced new SPS resin, possessing a 2-(ortho-nitrophenyl)ethanal linker, was used for the regioselective on-resin synthesis of N-mono-hydroxylated and N-mono-methylated polyamine spider toxins of Agelenopsis aperta and Larinioides folium. The polyamine backbones of the target compounds were efficiently constructed from the center by reductive amination of the aldehyde linker, followed by stepwise alkylation and acylation on solid support. Depending on the cleavage conditions, employing either oxidation/Cope elimination or methylation/Hofmann elimination, regioselectively the respective N-hydroxyl or N-methyl products were obtained. Employing this methodology, a number of acylpolyamine spider toxins were synthesized and identified as venom components by UHPLC and ESI-MS/MS.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. [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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  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. 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.

  1. [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.

  2. 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.

  3. IgG from Amyotrophic Lateral Sclerosis Patients Increases Current Through P-Type Calcium Channels in Mammalian Cerebellar Purkinje Cells and in Isolated Channel Protein in Lipid Bilayer

    NASA Astrophysics Data System (ADS)

    Llinas, R.; Sugimori, M.; Cherksey, B. D.; Smith, R. Glenn; Delbono, O.; Stefani, E.; Appel, S.

    1993-12-01

    The effect of the IgG from amyotrophic lateral sclerosis (ALS) patients was tested on the voltage-dependent barium currents (IBa) in mammalian dissociated Purkinje cells and in isolated P-type calcium channels in lipid bilayers. Whole cell clamp of Purkinje cells demonstrates that ALS IgG increases the amplitude of IBa without modifying their voltage kinetics. This increased IBa could be blocked by a purified nonpeptide toxin from Agelenopsis aperta venom (purified funnel-web spider toxin) or by a synthetic polyamine analog (synthetic funnel-web spider toxin) and by a peptide toxin from the same spider venom, ω-Aga-IVA. Similar results were obtained on single-channel recordings from purified P channel protein. The addition of ALS IgG increased single-channel IBa open time without affecting slope conductance. The results described above were not seen with normal human IgG nor with boiled ALS IgG. It is concluded that ALS IgG enhances inward current through P-type calcium channels. Since P-type Ca2+ channels are present in motoneuron axon terminals, we propose that the enhanced calcium current triggered by ALS IgG may contribute to neuronal damage in ALS.

  4. Unique Bell-shaped Voltage-dependent Modulation of Na+ Channel Gating by Novel Insect-selective Toxins from the Spider Agelena orientalis*

    PubMed Central

    Billen, Bert; Vassilevski, Alexander; Nikolsky, Anton; Debaveye, Sarah; Tytgat, Jan; Grishin, Eugene

    2010-01-01

    Spider venoms provide a highly valuable source of peptide toxins that act on a wide diversity of membrane-bound receptors and ion channels. In this work, we report isolation, biochemical analysis, and pharmacological characterization of a novel family of spider peptide toxins, designated β/δ-agatoxins. These toxins consist of 36–38 amino acid residues and originate from the venom of the agelenid funnel-web spider Agelena orientalis. The presented toxins show considerable amino acid sequence similarity to other known toxins such as μ-agatoxins, curtatoxins, and δ-palutoxins-IT from the related spiders Agelenopsis aperta, Hololena curta, and Paracoelotes luctuosus. β/δ-Agatoxins modulate the insect NaV channel (DmNaV1/tipE) in a unique manner, with both the activation and inactivation processes being affected. The voltage dependence of activation is shifted toward more hyperpolarized potentials (analogous to site 4 toxins) and a non-inactivating persistent Na+ current is induced (site 3-like action). Interestingly, both effects take place in a voltage-dependent manner, producing a bell-shaped curve between −80 and 0 mV, and they are absent in mammalian NaV channels. To the best of our knowledge, this is the first detailed report of peptide toxins with such a peculiar pharmacological behavior, clearly indicating that traditional classification of toxins according to their binding sites may not be as exclusive as previously assumed. PMID:20385552

  5. Unique bell-shaped voltage-dependent modulation of Na+ channel gating by novel insect-selective toxins from the spider Agelena orientalis.

    PubMed

    Billen, Bert; Vassilevski, Alexander; Nikolsky, Anton; Debaveye, Sarah; Tytgat, Jan; Grishin, Eugene

    2010-06-11

    Spider venoms provide a highly valuable source of peptide toxins that act on a wide diversity of membrane-bound receptors and ion channels. In this work, we report isolation, biochemical analysis, and pharmacological characterization of a novel family of spider peptide toxins, designated beta/delta-agatoxins. These toxins consist of 36-38 amino acid residues and originate from the venom of the agelenid funnel-web spider Agelena orientalis. The presented toxins show considerable amino acid sequence similarity to other known toxins such as mu-agatoxins, curtatoxins, and delta-palutoxins-IT from the related spiders Agelenopsis aperta, Hololena curta, and Paracoelotes luctuosus. beta/delta-Agatoxins modulate the insect Na(V) channel (DmNa(V)1/tipE) in a unique manner, with both the activation and inactivation processes being affected. The voltage dependence of activation is shifted toward more hyperpolarized potentials (analogous to site 4 toxins) and a non-inactivating persistent Na(+) current is induced (site 3-like action). Interestingly, both effects take place in a voltage-dependent manner, producing a bell-shaped curve between -80 and 0 mV, and they are absent in mammalian Na(V) channels. To the best of our knowledge, this is the first detailed report of peptide toxins with such a peculiar pharmacological behavior, clearly indicating that traditional classification of toxins according to their binding sites may not be as exclusive as previously assumed.

  6. 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

  7. 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

  8. 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.

  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. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. [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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. On the venom system of centipedes (Chilopoda), a neglected group of venomous animals.

    PubMed

    Undheim, Eivind A B; King, Glenn F

    2011-03-15

    Centipedes are among the oldest extant terrestrial arthropods and are an ecologically important group of soil and leaf litter predators. Despite their abundance and frequent, often painful, encounters with humans, little is known about the venom and venom apparatus of centipedes, although it is apparent that these are both quite different from other venomous lineages. The venom gland can be regarded as an invaginated cuticle and epidermis, consisting of numerous epithelial secretory units each with its own unique valve-like excretory system. The venom contains several different enzymes, but is strikingly different to most other arthropods in that metalloproteases appear to be important. Myotoxic, cardiotoxic, and neurotoxic activities have been described, most of which have been attributed to high molecular weight proteins. Neurotoxic activities are also unusual in that G-protein coupled receptors often seem to be involved, either directly as targets of neurotoxins or indirectly by activating endogenous agonists. These relatively slow responses may be complemented by the rapid effects caused by histamines present in the venom and from endogenous release of histamines induced by venom cytotoxins. The differences probably reflect the ancient and independent evolutionary history of the centipede venom system, although they may also be somewhat exaggerated by the paucity of information available on this largely neglected group.

  12. 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

  13. 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.

  14. 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)

  15. A spider toxin, ω-agatoxin IV A, binds to fixed as well as living tissues: cytochemical visualization of P/Q-type calcium channels.

    PubMed

    Nakanishi, Setsuko

    2016-08-01

    ω-Agatoxin IV A, a peptidyl toxin from Agelenopsis aperta venom, selectively binds to voltage-gated P/Q-type calcium channels. ω-Agatoxin IV A has been used as a selective tool in pharmacological and electrophysiological studies. Visualization of P/Q-type calcium channels has previously been accomplished using biotin-conjugated ω-Agatoxin IV A in freshly prepared mouse cerebellar and hippocampal slices (Nakanishi et al, J. Neurosci. Res., 41: , 532, 1995). Here biotinylated ω-agatoxin IV A was applied to transcardially fixed brain slices prepared with various fixatives. ω-Agatoxin IV A did not bind to fixed tissues from P/Q-type calcium channel knockout mice, confirming that binding to normal, fixed tissues was not an artifact. Using transmission electron microscopy, locations of biotinylated ω-agatoxin IV A binding sites visualized with gold-conjugated streptavidin showed a similar pattern to those visualized with antibody. The ability of biotinylated ω-agatoxin IV A to bind to fixed tissue provides a new cytochemical technique to study molecular architecture of synapses.

  16. 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

  17. 21 CFR 864.8950 - Russell viper venom reagent.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Russell viper venom reagent. 864.8950 Section 864...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8950 Russell viper venom reagent. (a) Identification. Russell viper venom reagent is a device used to determine the cause of...

  18. 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

  19. 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.

  20. 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.

  1. [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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. Dynamic evolution of venom proteins in squamate reptiles.

    PubMed

    Casewell, Nicholas R; Huttley, Gavin A; Wüster, Wolfgang

    2012-01-01

    Phylogenetic analyses of toxin gene families have revolutionised our understanding of the origin and evolution of reptile venoms, leading to the current hypothesis that venom evolved once in squamate reptiles. However, because of a lack of homologous squamate non-toxin sequences, these conclusions rely on the implicit assumption that recruitments of protein families into venom are both rare and irreversible. Here we use sequences of homologous non-toxin proteins from two snake species to test these assumptions. Phylogenetic and ancestral-state analyses revealed frequent nesting of 'physiological' proteins within venom toxin clades, suggesting early ancestral recruitment into venom followed by reverse recruitment of toxins back to physiological roles. These results provide evidence that protein recruitment into venoms from physiological functions is not a one-way process, but dynamic, with reversal of function and/or co-expression of toxins in different tissues. This requires a major reassessment of our previous understanding of how animal venoms evolve.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. [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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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).

  8. 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

  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

    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

  11. 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

  12. Detection and Identification of Vipera Russelli Venom

    DTIC Science & Technology

    1990-01-01

    immunoassay for measurement of infectious feline leukemia virus and its neutralization. J. Immunol. Methods 114: 253-260. UNCLASSIFIED UNCLASSIFIED 14 15...antigens and antibodies in parasitic as well as infectious diseases (1, 2). Attempts have been made to opti- mize sensitivity without compromising the...collected from these mice so blood collected from the peritoneal cavity was tested for presence of venom. This blood sample was hemolysed and showed high

  13. 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)

  14. 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

  15. 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.

  16. 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

  17. 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).

  18. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  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. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  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. 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

  20. 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.

  1. [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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Animal Venoms as a Source of Natural Antimicrobials: An overview.

    PubMed

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

    2017-03-10

    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 is 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.

  8. 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.

  9. 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

  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. 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.

  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.

  13. 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

  14. 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.

  15. Anticoagulant and antifibrinogenolytic properties of the aqueous extract from Bauhinia forficata against snake venoms.

    PubMed

    Oliveira, Clayton Z; Maiorano, Victor A; Marcussi, Silvana; Sant'ana, Carolina D; Januário, Ana H; Lourenço, Miriam V; Sampaio, Suely V; França, Suzelei C; Pereira, Paulo S; Soares, Andreimar M

    2005-04-08

    The aqueous extract from aerial parts of Bauhinia forficata was able to neutralize the clotting activity induced by Bothrops and Crotalus crude venoms. The clotting time, upon human plasma, induced by B. moojeni venom was significantly prolonged. Clotting and fibrinogenolytic activities induced by isolated thrombin-like enzyme from Bothrops jararacussu were totally inhibited after incubation at different ratios. The extract was not able to neutralize the hemorrhagic activity induced by an Bothrops venoms, but it efficiently inhibited the edema induced by Crotalus durissus terrificus venom and isolated PLA2s. In addition, it did not inhibited the phospholipase A2 activity of Bothrops snake venoms. Interaction studies between Bauhinia forficata extract and snake venoms, when analyzed by SDS-PAGE, did not reveal any apparent degradation of the venom proteins. This extract is a promising source of natural inhibitors of serine-proteases involved in blood clotting disturbances induced by snake venoms.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. Solution structure of two insect-specific spider toxins and their pharmacological interaction with the insect voltage-gated Na+ channel.

    PubMed

    Ferrat, G; Bosmans, F; Tytgat, J; Pimentel, C; Chagot, B; Gilles, N; Nakajima, T; Darbon, H; Corzo, G

    2005-05-01

    Delta-paluIT1 and delta-paluIT2 are toxins purified from the venom of the spider Paracoelotes luctuosus. Similar in sequence to mu-agatoxins from Agelenopsis aperta, their pharmacological target is the voltage-gated insect sodium channel, of which they alter the inactivation properties in a way similar to alpha-scorpion toxins, but they bind on site 4 in a way similar to beta-scorpion toxins. We determined the solution structure of the two toxins by use of two-dimensional nuclear magnetic resonance (NMR) techniques followed by distance geometry and molecular dynamics. The structures of delta-paluIT1 and delta-paluIT2 belong to the inhibitory cystine knot structural family, i.e. a compact disulfide-bonded core from which four loops emerge. Delta-paluIT1 and delta-paluIT2 contain respectively two- and three-stranded anti-parallel beta-sheets as unique secondary structure. We compare the structure and the electrostatic anisotropy of those peptides to other sodium and calcium channel toxins, analyze the topological juxtaposition of key functional residues, and conclude that the recognition of insect voltage-gated sodium channels by these toxins involves the beta-sheet, in addition to loops I and IV. Besides the position of culprit residues on the molecular surface, difference in dipolar moment orientation is another determinant of receptor binding and biological activity differences. We also demonstrate by electrophysiological experiments on the cloned insect voltage-gated sodium channel, para, heterologuously co-expressed with the tipE subunit in Xenopus laevis oocytes, that delta-paluIT1 and delta-paluIT2 procure an increase of Na+ current. delta-PaluIT1-OH seems to have less effect when the same concentrations are used.

  4. P/Q-type calcium channel modulators

    PubMed Central

    Nimmrich, V; Gross, G

    2012-01-01

    P/Q-type calcium channels are high-voltage-gated calcium channels contributing to vesicle release at synaptic terminals. A number of neurological diseases have been attributed to malfunctioning of P/Q channels, including ataxia, migraine and Alzheimer's disease. To date, only two specific P/Q-type blockers are known: both are peptides deriving from the spider venom of Agelenopsis aperta, ω-agatoxins. Other peptidic calcium channel blockers with activity at P/Q channels are available, albeit with less selectivity. A number of low molecular weight compounds modulate P/Q-type currents with different characteristics, and some exhibit a peculiar bidirectional pattern of modulation. Interestingly, there are a number of therapeutics in clinical use, which also show P/Q channel activity. Because selectivity as well as the exact mode of action is different between all P/Q-type channel modulators, the interpretation of clinical and experimental data is complicated and needs a comprehensive understanding of their target profile. The situation is further complicated by the fact that information on potency varies vastly in the literature, which may be the result of different experimental systems, conditions or the splice variants of the P/Q channel. This review attempts to provide a comprehensive overview of the compounds available that affect the P/Q-type channel and should help with the interpretation of results of in vitro experiments and animal models. It also aims to explain some clinical observations by implementing current knowledge about P/Q channel modulation of therapeutically used non-selective drugs. Chances and challenges of the development of P/Q channel-selective molecules are discussed. PMID:22670568

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. Pharmacological characterization of Synoeca cyanea venom: an aggressive social wasp widely distributed in the Neotropical region.

    PubMed

    Mortari, Márcia Renata; do Couto, Lucianna Lopes; dos Anjos, Lilian Carneiro; Mourão, Caroline Barbosa Farias; Camargos, Thalita Soares; Vargas, Jimmy Alexander Guerrero; Oliveira, Fagner Neves; Gati, Christiano Del Cantoni; Schwartz, Carlos Alberto; Schwartz, Elisabeth Ferroni

    2012-01-01

    The venom of social wasps has been poorly studied so far, despite the high number of accidents in humans and assessment of the use of these wasps as a biological control of pests. The study of the pharmacological effects of the venom is of great importance since the poisoning is dangerous causing serious systemic effects, including death in the case of multiple attacks. In this study, the pharmacological activities of venom from the social wasp Synoeca cyanea were evaluated by the following assays: LD50 in mice, the behavioural effects and the hemorrhagic activity induced by the venom in mice, the oedematogenic activity in rat, the haemolysis in human blood, the stimulating effect on guinea-pig smooth muscle, and the antimicrobial activity. The aim was to determine the toxic effects of venom and to perform a comparative study with earlier work conducted with venom from other wasp species. Results showed that S. cyanea venom produced a potent dose-dependent oedema, as well as antibacterial and haemolytic activities, suggesting the presence of histamine, serotonin, kinins and other molecules related to increased vascular permeability and cytolytic activity in this venom. Despite previous studies with wasp venoms, S. cyanea venom presented a slight hemorrhagic effect. Data obtained in the smooth muscle assay also suggest the presence of BK or analogues in S. cyanea whole venom. The knowledge of symptoms and effects produced by S. cyanea venom is critical for health organizations, in order to improve clinical treatment in accidents caused by wasp stings.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. Exon Shuffling and Origin of Scorpion Venom Biodiversity

    PubMed Central

    Wang, Xueli; Gao, Bin; Zhu, Shunyi

    2016-01-01

    Scorpion venom is a complex combinatorial library of peptides and proteins with multiple biological functions. A combination of transcriptomic and proteomic techniques has revealed its enormous molecular diversity, as identified by the presence of a large number of ion channel-targeted neurotoxins with different folds, membrane-active antimicrobial peptides, proteases, and protease inhibitors. Although the biodiversity of scorpion venom has long been known, how it arises remains unsolved. In this work, we analyzed the exon-intron structures of an array of scorpion venom protein-encoding genes and unexpectedly found that nearly all of these genes possess a phase-1 intron (one intron located between the first and second nucleotides of a codon) near the cleavage site of a signal sequence despite their mature peptides remarkably differ. This observation matches a theory of exon shuffling in the origin of new genes and suggests that recruitment of different folds into scorpion venom might be achieved via shuffling between body protein-coding genes and ancestral venom gland-specific genes that presumably contributed tissue-specific regulatory elements and secretory signal sequences. PMID:28035955

  2. Target tracking during venom ‘spitting’ by cobras

    PubMed Central

    Westhoff, Guido; Boetig, Melissa; Bleckmann, Horst; Young, Bruce A.

    2010-01-01

    Spitting cobras, which defend themselves by streaming venom towards the face and/or eyes of a predator, must be highly accurate because the venom they spit is only an effective deterrent if it lands on the predator's cornea. Several factors make this level of accuracy difficult to achieve; the target is moving, is frequently >1 m away from the snake and the venom stream is released in approximately 50 ms. In the present study we show that spitting cobras can accurately track the movements of a potentially threatening vertebrate, and by anticipating its subsequent (short-term) movements direct their venom to maximize the likelihood of striking the target's eye. Unlike other animals that project material, in spitting cobras the discharge orifice (the fang) is relatively fixed so directing the venom stream requires rapid movements of the entire head. The cobra's ability to track and anticipate the target's movement, and to perform rapid cephalic oscillations that coordinate with the target's movements suggest a level of neural processing that has not been attributed to snakes, or other reptiles, previously. PMID:20472765

  3. Facing Hymenoptera Venom Allergy: From Natural to Recombinant Allergens

    PubMed Central

    Perez-Riverol, Amilcar; Justo-Jacomini, Débora Lais; Zollner, Ricardo de Lima; Brochetto-Braga, Márcia Regina

    2015-01-01

    Along with food and drug allergic reactions, a Hymenoptera insect Sting (Apoidea, Vespidae, Formicidae) is one of the most common causes of anaphylaxis worldwide. Diagnoses of Hymenoptera venom allergy (HVA) and specific immunotherapy (SIT) have been based on the use of crude venom extracts. However, the incidence of cross-reactivity and low levels of sensibility during diagnosis, as well as the occurrence of nonspecific sensitization and undesired side effects during SIT, encourage the search for novel allergenic materials. Recombinant allergens are an interesting approach to improve allergy diagnosis and SIT because they circumvent major problems associated with the use of crude venom. Production of recombinant allergens depends on the profound molecular characterization of the natural counterpart by combining some “omics” approaches with high-throughput screening techniques and the selection of an appropriate system for heterologous expression. To date, several clinically relevant allergens and novel venom toxins have been identified, cloned and characterized, enabling a better understanding of the whole allergenic and envenoming processes. Here, we review recent findings on identification, molecular characterization and recombinant expression of Hymenoptera venom allergens and on the evaluation of these heterologous proteins as valuable tools for tackling remaining pitfalls on HVA diagnosis and immunotherapy. PMID:26184309

  4. Tetracycline Reduces Kidney Damage Induced by Loxosceles Spider Venom

    PubMed Central

    Okamoto, Cinthya Kimori; van den Berg, Carmen W.; Masashi, Mizuno; Gonçalves-de-Andrade, Rute M.; Tambourgi, Denise V.

    2017-01-01

    Envenomation by Loxosceles spider can result in two clinical manifestations: cutaneous and systemic loxoscelism, the latter of which includes renal failure. Although incidence of renal failure is low, it is the main cause of death, occurring mainly in children. The sphingomyelinase D (SMase D) is the main component in Loxosceles spider venom responsible for local and systemic manifestations. This study aimed to investigate the toxicity of L. intermedia venom and SMase D on kidney cells, using both In vitro and in vivo models, and the possible involvement of endogenous metalloproteinases (MMP). Results demonstrated that venom and SMase D are able to cause death of human kidney cells by apoptosis, concomitant with activation and secretion of extracellular matrix metalloproteases, MMP-2 and MMP-9. Furthermore, cell death and MMP synthesis and secretion can be prevented by tetracycline. In a mouse model of systemic loxoscelism, Loxosceles venom-induced kidney failure was observed, which was abrogated by administration of tetracycline. These results indicate that MMPs may play an important role in Loxosceles venom-induced kidney injury and that tetracycline administration may be useful in the treatment of human systemic loxoscelism. PMID:28257106

  5. Gamma irradiation of Egyptian Cobra (Naja haje) Venom.

    PubMed

    Shaban, E A; Ahmed, A A; Ayobe, M H

    1996-01-01

    The aim of the present study was to prepare an effective and safe toxoid for the Egyptian Cobra (Naja haje) Venom by gamma irradiation. The effects of gamma irradiation (0.1-10 M rad) on the toxicity, as well as the antigen antibody complex formation reactivity was described. It appears from the results that the lethality of Naja haje venom irradiated in the dry form was not affected up to a dose of 10 M rad (100 KGy). On the other hand, the venom irradiated in the aqueous solution form showed a decrease in its lethality, and this was proportionately related to the dose of irradiation, while the ability of the venom antigens to react with its corresponding antibodies was retained up to irradiation dose of 5 M rad. The results of double immunodiffusion of non irradiated and the different dose levels of gamma irradiated venom (0.1-5 M rad) against a commercial Egyptian polyvalent antivenin, all showed similar patterns, the four visible lines obtained in the immunodiffusion reactions were identical and joined smoothly at the corners, indicating that there was no change in antigenic reactivity with antibodies determinants.

  6. Tetracycline Reduces Kidney Damage Induced by Loxosceles Spider Venom.

    PubMed

    Okamoto, Cinthya Kimori; van den Berg, Carmen W; Masashi, Mizuno; Gonçalves-de-Andrade, Rute M; Tambourgi, Denise V

    2017-03-02

    Envenomation by Loxosceles spider can result in two clinical manifestations: cutaneous and systemic loxoscelism, the latter of which includes renal failure. Although incidence of renal failure is low, it is the main cause of death, occurring mainly in children. The sphingomyelinase D (SMase D) is the main component in Loxosceles spider venom responsible for local and systemic manifestations. This study aimed to investigate the toxicity of L. intermedia venom and SMase D on kidney cells, using both In vitro and in vivo models, and the possible involvement of endogenous metalloproteinases (MMP). Results demonstrated that venom and SMase D are able to cause death of human kidney cells by apoptosis, concomitant with activation and secretion of extracellular matrix metalloproteases, MMP-2 and MMP-9. Furthermore, cell death and MMP synthesis and secretion can be prevented by tetracycline. In a mouse model of systemic loxoscelism, Loxosceles venom-induced kidney failure was observed, which was abrogated by administration of tetracycline. These results indicate that MMPs may play an important role in Loxosceles venom-induced kidney injury and that tetracycline administration may be useful in the treatment of human systemic loxoscelism.

  7. Scorpion venom components that affect ion-channels function

    PubMed Central

    Quintero-Hernández, V.; Jiménez-Vargas, J.M.; Gurrola, G.B.; Valdivia, H.H.F.; Possani, L.D.

    2014-01-01

    SUMMARY The number and types of venom components that affect ion-channel function are reviewed. These are the most important venom components responsible for human intoxication, deserving medical attention, often requiring the use of specific anti-venoms. Special emphasis is given to peptides that recognize Na+-, K+- and Ca++-channels of excitable cells. Knowledge generated by direct isolation of peptides from venom and components deduced from cloned genes, whose amino acid sequences are deposited into databanks are now adays in the order of 1.5 thousands, out of an estimate biodiversity closed to 300,000. Here the diversity of components is briefly reviewed with mention to specific references. Structural characteristic are discussed with examples taken from published work. The principal mechanisms of action of the three different types of peptides are also reviewed. Na+-channel specific venom components usually are modifier of the open and closing kinetic mechanisms of the ion-channels, whereas peptides affecting K+-channels are normally pore blocking agents. The Ryanodine Ca++-channel specific peptides are known for causing sub-conducting stages of the channels conductance and some were shown to be able to internalize penetrating inside the muscle cells. PMID:23891887

  8. Facing Hymenoptera Venom Allergy: From Natural to Recombinant Allergens.

    PubMed

    Perez-Riverol, Amilcar; Justo-Jacomini, Débora Lais; Zollner, Ricardo de Lima; Brochetto-Braga, Márcia Regina

    2015-07-09

    Along with food and drug allergic reactions, a Hymenoptera insect Sting (Apoidea, Vespidae, Formicidae) is one of the most common causes of anaphylaxis worldwide. Diagnoses of Hymenoptera venom allergy (HVA) and specific immunotherapy (SIT) have been based on the use of crude venom extracts. However, the incidence of cross-reactivity and low levels of sensibility during diagnosis, as well as the occurrence of nonspecific sensitization and undesired side effects during SIT, encourage the search for novel allergenic materials. Recombinant allergens are an interesting approach to improve allergy diagnosis and SIT because they circumvent major problems associated with the use of crude venom. Production of recombinant allergens depends on the profound molecular characterization of the natural counterpart by combining some "omics" approaches with high-throughput screening techniques and the selection of an appropriate system for heterologous expression. To date, several clinically relevant allergens and novel venom toxins have been identified, cloned and characterized, enabling a better understanding of the whole allergenic and envenoming processes. Here, we review recent findings on identification, molecular characterization and recombinant expression of Hymenoptera venom allergens and on the evaluation of these heterologous proteins as valuable tools for tackling remaining pitfalls on HVA diagnosis and immunotherapy.

  9. 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.

  10. 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.

  11. 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.

  12. A review of venomous animal bites and stings in pregnant patients.

    PubMed

    Langley, Ricky Lee

    2004-01-01

    This is a review of Medline and PubMed articles on venomous animal bites and stings during pregnancy reported in English literature from 1966 to 2002. Eighty-five venomous snakebites were reported in pregnant women. Although there are frequent anecdotal reports of scorpion stings in pregnant women, few case reports are documented. Other venomous animal bites or stings to pregnant women that have been reported include spiders, jellyfish, and insects, and these are described. Adverse reproductive and teratogenic effects of venoms on gravid animals are also briefly reviewed. Although uncommon, venomous bites and stings during pregnancy may have significant adverse effects on the fetus and the mother.

  13. Proteomic analysis of venom variability and ontogeny across the arboreal palm-pitvipers (genus Bothriechis).

    PubMed

    Pla, Davinia; Sanz, Libia; Sasa, Mahmood; Acevedo, Manuel E; Dwyer, Quetzal; Durban, Jordi; Pérez, Alicia; Rodriguez, Yania; Lomonte, Bruno; Calvete, Juan J

    2017-01-30

    Bothriechis is a genus of eleven currently recognized slender and arboreal venomous snakes, commonly called palm-pitvipers that range from southern Mexico to northern South America. Despite dietary studies suggesting that palm-pitvipers are generalists with an ontogenetic shift toward endothermic prey, venom proteomic analyses have revealed remarkable divergence between the venoms of the Costa Rican species, B. lateralis, B. schlegelii, B. supraciliaris, and B. nigroviridis. To achieve a more complete picture of the venomic landscape across Bothriechis, the venom proteomes of biodiversity of the northern Middle American highland palm-pitvipers, B. thalassinus, B. aurifer, and B. bicolor from Guatemala, B. marchi from Honduras, and neonate Costa Rican B. lateralis and B. schlegelii, were investigated. B. thalassinus and B. aurifer venoms are comprised by similar toxin arsenals dominated by SVMPs (33-39% of the venom proteome), CTLs (11-16%), BPP-like molecules (10-13%), and CRISPs (5-10%), and are characterized by the absence of PLA2 proteins. Conversely, the predominant (35%) components of B. bicolor are D49-PLA2 molecules. The venom proteome of B. marchi is similar to B. aurifer and B. thalassinus in that it is rich in SVMPs and BPPs, but also contains appreciable amounts (14.3%) of PLA2s. The major toxin family found in the venoms of both neonate B. lateralis and B. schlegelii, is serine proteinase (SVSP), comprising about 20% of their toxin arsenals. The venom of neonate B. schlegelii is the only palm-pitviper venom where relative high amounts of Kunitz-type (6.3%) and γPLA2 (5.2%) inhibitors have been identified. Despite notable differences between their proteomes, neonate venoms are more similar to each other than to adults of their respective species. However, the ontogenetic changes taking place in the venom of B. lateralis strongly differ from those that occur in the venom of B. schlegelii. Thus, the ontogenetic change in B. lateralis produces a SVMP

  14. [Pharmacologic and enzymatic effects of snake venoms from Antioquia and Choco (Colombia)].

    PubMed

    Otero, R; Guillermo Osorio, R; Valderrama, R; Augusto Giraldo, C

    1992-01-01

    We compared several pharmacological and enzymatic effects induced by 11 snake venoms from seven species, six of them from different geographic areas of Antioquia and Choco, north-west of Colombia, South America (Bothrops atrox, B. nasutus, B. schlegelii, B. punctatus, Lachesis muta, Micrurus mipartitus), and Crotalus durissus terrificus venom, from specimens captured in other provinces of the country (Tolima, Huila, Meta and Atlantico). Differences were observed in edema-forming, hemorrhage, defibrination, indirect hemolysis, myonecrosis, proteolysis and lethal activity between venoms from different genera or species, as well as according to the geographic area of origin in B. atrox and B. nasutus snake venoms. Bothrops venoms, in particular B. atrox and L. muta, produced major local effects. All of the venoms, including M. mipartitus, had myotoxic effects. The most defibrinating venoms were B. atrox, L. muta, B. punctatus and C. d. terrificus. All of the venoms had indirect hemolytic activity; the venom of M. mipartitus being greatest. The most lethal venoms were those of C. d. terrificus and M. mipartitus. Within Bothrops species, the venom of B. schlegelii was the least active in terms of local and systemic pathologic effects.

  15. Proteomic analysis of the venom from the endoparasitoid wasp Pteromalus puparum (Hymenoptera: Pteromalidae).

    PubMed

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

    2010-09-01

    Parasitoid venom is a complex mixture of active substances with diversified biological functions. Because of its range of activities, venom is an important resource with respect to potential application in agriculture and medicine. Only a limited number of peptides, proteins, and enzymes have been identified and characterized from parasitoid venom. Here we describe a proteomic analysis of the venom from the endoparasitoid wasp Pteromalus puparum (Hymenoptera: Pteromalidae). Venom resolved by two-dimensional electrophoresis yielded 56 protein spots with major proteins in the pI range 4-7 and molecular mass range of 25-66.2 kDa. The amino acid sequences of the proteins were identified by mass spectrometry. Several venom proteins such as calreticulin, venom acid phosphatase, serine protease, arginine kinase, serine protease homolog, aminotransferase-like venom protein, and heat shock protein 70, were identified in silico based on their amino acid sequences. The full-length cDNAs of calreticulin and arginine kinase were cloned. Calreticulin showed 62% identity with calreticulin in the venom of Cotesia rubecula. Arginine kinase showed a high level of sequence identity (92%) with its counterpart in the venom of Cyphononyx dorsalis. RT-PCR analysis revealed that the transcript levels of calreticulin and arginine kinase were developmentally changed, suggesting a possible correlation with the oviposition process. This study contributes to our appreciation of a parasitoid wasp venom composition.

  16. Analysis of Protein Composition and Bioactivity of Neoponera villosa Venom (Hymenoptera: Formicidae)

    PubMed Central

    Pessoa, Wallace Felipe Blohem; Silva, Ludimilla Carvalho Cerqueira; de Oliveira Dias, Leila; Delabie, Jacques Hubert Charles; Costa, Helena; Romano, Carla Cristina

    2016-01-01

    Ants cause a series of accidents involving humans. Such accidents generate different reactions in the body, ranging from a mild irritation at the bite site to anaphylactic shock, and these reactions depend on the mechanism of action of the venom. The study of animal venom is a science known as venomics. Through venomics, the composition of the venom of several ant species has already been characterized and their biological activities described. Thus, the aim of this study was to evaluate the protein composition and biological activities (hemolytic and immunostimulatory) of the venom of Neoponera villosa (N. villosa), an ant widely distributed in South America. The protein composition was evaluated by proteomic techniques, such as two-dimensional electrophoresis. To assess the biological activity, hemolysis assay was carried out and cytokines were quantified after exposure of macrophages to the venom. The venom of N. villosa has a profile composed of 145 proteins, including structural and metabolic components (e.g., tubulin and ATPase), allergenic and immunomodulatory proteins (arginine kinase and heat shock proteins (HSPs)), protective proteins of venom (superoxide dismutase (SOD) and catalase) and tissue degradation proteins (hyaluronidase and phospholipase A2). The venom was able to induce hemolysis in human erythrocytes and also induced release of both pro-inflammatory cytokines, as the anti-inflammatory cytokine release by murine macrophages. These results allow better understanding of the composition and complexity of N. villosa venom in the human body, as well as the possible mechanisms of action after the bite. PMID:27110765

  17. Identification and characterization of venom proteins of two solitary wasps, Eumenes pomiformis and Orancistrocerus drewseni.

    PubMed

    Baek, Ji Hyeong; Lee, Si Hyeock

    2010-09-15

    Secretory proteins were identified in the venoms of two solitary hunting wasps, Eumenes pomiformis and Orancistrocerus drewseni, by SDS-PAGE in conjunction with mass analysis. More than 30 protein bands (2-300 kDa) were detected from the crude venom of each wasp. With the aid of the previously constructed venom gland/sac-specific EST libraries, a total of 31 and 20 proteins were identified from 18 to 20 distinctive protein bands of E. pomiformis and O. drewseni venoms, respectively. Arginine kinase was the most predominant protein in both wasp venoms. Along with the full-length arginine kinase, a truncated form, which was known to have paralytic activity on a spider, was a common predominant protein in the two wasp venoms. Insulin/insulin-like peptide-binding protein was abundantly found only in E. pomiformis venom, which might be due to its unique behaviors of oviposition and provision. The presence of various immune response-related proteins and antioxidants suggested that wasps might use their venom to maintain prey fresh while feeding wasp larvae by protecting the prey from microbial invasion and physiological stresses. It seemed that some venom proteins are secreted into venom fluid from venom gland cells via exosomes, not by signal sequence-mediated transport processes.

  18. The Triterpenoid Betulin Protects against the Neuromuscular Effects of Bothrops jararacussu Snake Venom In Vivo

    PubMed Central

    Ferraz, Miriéle Cristina; de Oliveira, Jhones Luiz; de Oliveira Junior, Joel Reis; Cogo, José Carlos; dos Santos, Márcio Galdino; Franco, Luiz Madaleno; Puebla, Pilar; Ferraz, Helena Onishi; Ferraz, Humberto Gomes; da Rocha, Marisa Maria Teixeira; Hyslop, Stephen; San Feliciano, Arturo; Oshima-Franco, Yoko

    2015-01-01

    We confirmed the ability of the triterpenoid betulin to protect against neurotoxicity caused by Bothrops jararacussu snake venom in vitro in mouse isolated phrenic nerve-diaphragm (PND) preparations and examined its capability of in vivo protection using the rat external popliteal/sciatic nerve-tibialis anterior (EPSTA) preparation. Venom caused complete, irreversible blockade in PND (40 μg/mL), but only partial blockade (~30%) in EPSTA (3.6 mg/kg, i.m.) after 120 min. In PND, preincubation of venom with commercial bothropic antivenom (CBA) attenuated the venom-induced blockade, and, in EPSTA, CBA given i.v. 15 min after venom also attenuated the blockade (by ~70% in both preparations). Preincubation of venom with betulin (200 μg/mL) markedly attenuated the venom-induced blockade in PND; similarly, a single dose of betulin (20 mg, i.p., 15 min after venom) virtually abolished the venom-induced decrease in contractility. Plasma creatine kinase activity was significantly elevated 120 min after venom injection in the EPSTA but was attenuated by CBA and betulin. These results indicate that betulin given i.p. has a similar efficacy as CBA given i.v. in attenuating the neuromuscular effects of B. jararacussu venom in vivo and could be a useful complementary measure to antivenom therapy for treating snakebite. PMID:26633987

  19. Mechanisms controlling venom expulsion in the western diamondback rattlesnake, Crotalus atrox.

    PubMed

    Young, Bruce A; Kardong, Kenneth V

    2007-01-01

    Although many studies have documented variation in the amount of venom expended during bites of venomous snakes, the mechanistic source of this variation remains uncertain. This study used experimental techniques to examine how two different features of the venom delivery system, the muscle surrounding the venom gland (the Compressor Glandulae in the rattlesnake) and the fang sheath, could influence venom flow in the western diamondback rattlesnake, Crotalus atrox. Differential contraction of the Compressor Glandulae explained only approximately 30% of the variation in venom flow. Lifting (compression) of the fang sheath as occurs during a normal strike produced marked increases in venom flow; these changes were closely correlated and exceed in magnitude by almost 10 x those recorded from the Compressor Glandulae alone. These results suggest that variation in these two aspects of the venom delivery system--both in terms of magnitude and temporal patterning--explain most of the observed variation in venom injection. The lack of functional or mechanical links between the Compressor Glandulae and the fang sheath, and the lack of skeletal or smooth muscle within the fang sheath, make it unlikely that variation in venom flow is under direct neural control. Instead, differential venom injection results from differences in the pressurization by the Compressor Glandulae, the gate keeping effects of the fang sheath and enclosed soft-tissue chambers, and by differences in the pressure returned by peripheral resistance of the target tissue.

  20. The Triterpenoid Betulin Protects against the Neuromuscular Effects of Bothrops jararacussu Snake Venom In Vivo.

    PubMed

    Ferraz, Miriéle Cristina; de Oliveira, Jhones Luiz; de Oliveira Junior, Joel Reis; Cogo, José Carlos; Dos Santos, Márcio Galdino; Franco, Luiz Madaleno; Puebla, Pilar; Ferraz, Helena Onishi; Ferraz, Humberto Gomes; da Rocha, Marisa Maria Teixeira; Hyslop, Stephen; San Feliciano, Arturo; Oshima-Franco, Yoko

    2015-01-01

    We confirmed the ability of the triterpenoid betulin to protect against neurotoxicity caused by Bothrops jararacussu snake venom in vitro in mouse isolated phrenic nerve-diaphragm (PND) preparations and examined its capability of in vivo protection using the rat external popliteal/sciatic nerve-tibialis anterior (EPSTA) preparation. Venom caused complete, irreversible blockade in PND (40 μg/mL), but only partial blockade (~30%) in EPSTA (3.6 mg/kg, i.m.) after 120 min. In PND, preincubation of venom with commercial bothropic antivenom (CBA) attenuated the venom-induced blockade, and, in EPSTA, CBA given i.v. 15 min after venom also attenuated the blockade (by ~70% in both preparations). Preincubation of venom with betulin (200 μg/mL) markedly attenuated the venom-induced blockade in PND; similarly, a single dose of betulin (20 mg, i.p., 15 min after venom) virtually abolished the venom-induced decrease in contractility. Plasma creatine kinase activity was significantly elevated 120 min after venom injection in the EPSTA but was attenuated by CBA and betulin. These results indicate that betulin given i.p. has a similar efficacy as CBA given i.v. in attenuating the neuromuscular effects of B. jararacussu venom in vivo and could be a useful complementary measure to antivenom therapy for treating snakebite.

  1. Resistance of cervical adenocarcinoma cells (HeLa) to venom from the scorpion Centruroides limpidus limpidus

    PubMed Central

    2013-01-01

    Background The venom of Centruroides limpidus limpidus (Cll) is a mixture of pharmacologically active principles. The most important of these are toxic proteins that interact both selectively and specifically with different cellular targets such as ion channels. Recently, anticancer properties of the venom from other scorpion species have been described. Studies in vitro have shown that scorpion venom induces cell death, inhibits proliferation and triggers the apoptotic pathway in different cancer cell lines. Herein, after treating human cervical adenocarcinoma (HeLa) cells with Cll crude venom, their cytotoxic activity and apoptosis induction were assessed. Results Cll crude venom induced cell death in normal macrophages in a dose-dependent manner. However, through viability assays, HeLa cells showed high survival rates after exposure to Cll venom. Also, Cll venom did not induce apoptosis after performing ethidium bromide/acridine orange assays, nor was there any evidence of chromatin condensation or DNA fragmentation. Conclusions Crude Cll venom exposure was not detrimental to HeLa cell cultures. This may be partially attributable to the absence of specific HeLa cell membrane targets for molecules present in the venom of Centruroides limpidus limpidus. Although these results might discourage additional studies exploring the potential of Cll venom to treat human papilloma cervical cancer, further research is required to explore positive effects of crude Cll venom on other cancer cell lines. PMID:24004568

  2. General biochemical and immunological characteristics of the venom from Peruvian scorpion Hadruroides lunatus.

    PubMed

    Costal-Oliveira, F; Duarte, C G; Machado de Avila, R A; Melo, M M; Bordon, K C F; Arantes, E C; Paredes, N C; Tintaya, B; Bonilla, C; Bonilla, R E; Suarez, W S; Yarleque, A; Fernandez, J M; Kalapothakis, E; Chávez-Olórtegui, Carlos

    2012-10-01

    This communication describes the general biochemical properties and some immunological characteristics of the venom from the Peruvian scorpion Hadruroides lunatus, which is the most medically relevant species in Peru. The soluble venom of this scorpion is toxic to mice, the LD₅₀ determined was 0.1 mg/kg and 21.55 mg/kg when the venom was injected intracranial or intraperitoneally, respectively. The soluble venom displayed proteolytic, hyaluronidasic, phospholipasic and cardiotoxic activities. High performance liquid chromatography of the soluble venom resulted in the separation of 20 fractions. Two peptides with phospholipasic activity were isolated to homogeneity and their molecular masses determined by mass spectrometry (MALDI TOF). Anti-H. lunatus venom sera were produced in rabbits. Western blotting analysis showed that most of the protein content of this venom is immunogenic. H. lunatus anti-venom displayed consistent cross-reactivity with venom antigens from the new World-scorpions Tityus serrulatus and Centruroides sculpturatus venoms; however, a weaker reactivity was observed against the venom antigens from the old World-scorpion Androctonus australis Hector.

  3. The Effect of a Polyvalent Antivenom on the Serum Venom Antigen Levels of Naja sputatrix (Javan Spitting Cobra) Venom in Experimentally Envenomed Rabbits.

    PubMed

    Yap, Michelle Khai Khun; Tan, Nget Hong; Sim, Si Mui; Fung, Shin Yee; Tan, Choo Hock

    2015-10-01

    The treatment protocol of antivenom in snake envenomation remains largely empirical, partly due to the insufficient knowledge of the pharmacokinetics of snake venoms and the effects of antivenoms on the blood venom levels in victims. In this study, we investigated the effect of a polyvalent antivenom on the serum venom antigen levels of Naja sputatrix (Javan spitting cobra) venom in experimentally envenomed rabbits. Intravenous infusion of 4 ml of Neuro Polyvalent Snake Antivenom [NPAV, F(ab')2 ] at 1 hr after envenomation caused a sharp decline of the serum venom antigen levels, followed by transient resurgence an hour later. The venom antigen resurgence was unlikely to be due to the mismatch of pharmacokinetics between the F(ab')2 and venom antigens, as the terminal half-life and volume of distribution of the F(ab')2 in serum were comparable to that of venom antigens (p > 0.05). Infusion of an additional 2 ml of NPAV was able to prevent resurgence of the serum venom antigen level, resulting in a substantial decrease (67.1%) of the total amount of circulating venom antigens over time course of envenomation. Our results showed that the neutralization potency of NPAV determined by neutralization assay in mice may not be an adequate indicator of its capability to modulate venom kinetics in relation to its in vivo efficacy to neutralize venom toxicity. The findings also support the recommendation of giving high initial dose of NPAV in cobra envenomation, with repeated doses as clinically indicated in the presence of rebound antigenemia and symptom recurrence.

  4. [Influence of electromagnetic radiation on toxicity of Vipera lebetina obtusa venom].

    PubMed

    Abiev, G A; Babaev, E I; Topchieva, Sh A; Chumburidze, T B; Nemsitsveridze, N G

    2009-11-01

    The aim of the article was to study the effect of electromagnetic radiation on toxicity of Vipera lebetina obtusa venom. It was found that mice intoxicated with snake venom, with moderate to high exposure to electromagnetic radiation and mice intoxicated with venom, which had not been exposed to the radiation showed the same symptoms of intoxication and death. At the same time, the longevity of mice intoxicated with venom exposed to electromagnetic radiation was higher. The longevity of mice in control group was 25+/-5 min. The longevity of mice intoxicated with exposed to electromagnetic radiation snake venom was from 29 to 60 min. The research showed that the longevity of mice intoxicated with snake venom rose with the level of electromagnetic radiation intensity the snake was exposed to. Accordingly, snake venom, with exposure to high intensity electromagnetic radiation is less toxic.

  5. Cabinet of Curiosities: Venom Systems and Their Ecological Function in Mammals, with a Focus on Primates

    PubMed Central

    Rode-Margono, Johanna E.; Nekaris, K. Anne-Isola

    2015-01-01

    Venom delivery systems (VDS) are common in the animal kingdom, but rare amongst mammals. New definitions of venom allow us to reconsider its diversity amongst mammals by reviewing the VDS of Chiroptera, Eulipotyphla, Monotremata, and Primates. All orders use modified anterior dentition as the venom delivery apparatus, except Monotremata, which possesses a crural system. The venom gland in most taxa is a modified submaxillary salivary gland. In Primates, the saliva is activated when combined with brachial gland exudate. In Monotremata, the crural spur contains the venom duct. Venom functions include feeding, intraspecific competition, anti-predator defense and parasite defense. Including mammals in discussion of venom evolution could prove vital in our understanding protein functioning in mammals and provide a new avenue for biomedical and therapeutic applications and drug discovery. PMID:26193318

  6. Cabinet of Curiosities: Venom Systems and Their Ecological Function in Mammals, with a Focus on Primates.

    PubMed

    Rode-Margono, Johanna E; Nekaris, K Anne-Isola

    2015-07-17

    Venom delivery systems (VDS) are common in the animal kingdom, but rare amongst mammals. New definitions of venom allow us to reconsider its diversity amongst mammals by reviewing the VDS of Chiroptera, Eulipotyphla, Monotremata, and Primates. All orders use modified anterior dentition as the venom delivery apparatus, except Monotremata, which possesses a crural system. The venom gland in most taxa is a modified submaxillary salivary gland. In Primates, the saliva is activated when combined with brachial gland exudate. In Monotremata, the crural spur contains the venom duct. Venom functions include feeding, intraspecific competition, anti-predator defense and parasite defense. Including mammals in discussion of venom evolution could prove vital in our understanding protein functioning in mammals and provide a new avenue for biomedical and therapeutic applications and drug discovery.

  7. Venomous auger snail Hastula (Impages) hectica (Linnaeus, 1758): molecular phylogeny, foregut anatomy and comparative toxinology.

    PubMed

    Imperial, Julita S; Kantor, Yuri; Watkins, Maren; Heralde, Francisco M; Stevenson, Bradford; Chen, Ping; Hansson, Karin; Stenflo, Johan; Ownby, John-Paul; Bouchet, Philippe; Olivera, Baldomero M

    2007-12-15

    The >10,000 living venomous marine snail species [superfamily Conoidea (Fleming, 1822)] include cone snails (Conus), the overwhelming focus of research. Hastula hectica (Linnaeus, 1758), a venomous snail in the family Terebridae (Mörch, 1852) was comprehensively investigated. The Terebridae comprise a major monophyletic group within Conoidea. H. hectica has a striking radular tooth to inject venom that looks like a perforated spear; in Conus, the tooth looks like a hypodermic needle. H. hectica venom contains a large complement of small disulfide-rich peptides, but with no apparent overlap with Conus in gene superfamilies expressed. Although Conus peptide toxins are densely post-translationally modified, no post-translationally modified amino acids were found in any Hastula venom peptide. The results suggest that different major lineages of venomous molluscs have strikingly divergent toxinological and venom-delivery strategies.

  8. Analysis of intraspecific variation in venoms of Acanthophis antarcticus death adders from South Australia

    PubMed Central

    Herzig, Volker; Kohler, Maxie; Grund, Kai F; Reeve, Shane; Smith, A Ian; Hodgson, Wayne C

    2013-01-01

    Intraspecific variation in venom composition and activity has been reported from a wide range of snakes. Geographical origin can be one cause for this variation and has recently been documented from Acanthophis antarcticus death adders sampled across four different Australian states. The present study examined whether a narrower sampling range of A. antarcticus from four collection sites within one Australian state (i.e., South Australia) would also exhibit variation in venom composition and/or activity. The present LC-MS results reveal marked differences in the venom composition from different collection sites. The most striking difference was the reduced venom complexity found in the only venom originating from a mallee scrub habitat in comparison to the venoms from coastal heath scrub habitats. Interestingly, the pharmacological activity of all venoms was found to be the same, independent of the collection site. PMID:24163732

  9. A Novel Neurotoxin from Venom of the Spider, Brachypelma albopilosum

    PubMed Central

    Yuan, Mingwei; Li, Hongli; Wang, Ping; Yuan, Minglong; Lu, Qiumin

    2014-01-01

    Spiders have evolved highly selective toxins for insects. There are many insecticidal neurotoxins in spider venoms. Although a large amount of work has been done to focus on neurotoxicity of spider components, little information, which is related with effects of spider toxins on tumor cell proliferation and cytotoxicity, is available for Brachypelma albopilosum venom. In this work, a novel spider neurotoxin (brachyin) was identified and characterized from venoms of the spider, Brachypelma albopilosum. Brachyin is composed of 41 amino acid residues with the sequence of CLGENVPCDKDRPNCCSRYECLEPTGYGWWYASYYCYKKRS. There are six cysteines in this sequence, which form three disulfided bridges. The serine residue at the C-terminus is amidated. Brachyin showed strong lethal effects on American cockroaches (Periplaneta americana) and Tenebrio molitor (common mealbeetle). This neurotoxin also showed significant analgesic effects in mice models including abdominal writhing induced by acetic acid and formalin-induced paw licking tests. It was interesting that brachyin exerted marked inhibition on tumor cell proliferation. PMID:25329070

  10. Deciphering the Venomic Transcriptome of Killer-Wasp Vespa velutina

    PubMed Central

    Liu, Zhirui; Chen, Shuanggang; Zhou, You; Xie, Cuihong; Zhu, Bifeng; Zhu, Huming; Liu, Shupeng; Wang, Wei; Chen, Hongzhuan; Ji, Yonghua

    2015-01-01

    Wasp stings have been arising to be a severe public health problem in China in recent years. However, molecular information about lethal or toxic factors in wasp venom is extremely lacking. In this study, we used two pyrosequencing platforms to analyze the transcriptome of Vespa velutina, the most common wasp species native in China. Besides the substantial amount of transcripts encoding for allergens usually regarded as the major lethal factor of wasp sting, a greater abundance of hemostasis-impairing toxins and neurotoxins in the venom of V. velutina were identified, implying that toxic reactions and allergic effects are envenoming strategy for the dangerous outcomes. The pattern of differentially expressed genes before and after venom extraction clearly indicates that the manifestation of V. velutina stings depends on subtle regulations in the metabolic pathway required for toxin recruitment. This comparative analysis offers timely clues for developing clinical treatments for wasp envenoming in China and around the world. PMID:25896434

  11. Deciphering the venomic transcriptome of killer-wasp Vespa velutina.

    PubMed

    Liu, Zhirui; Chen, Shuanggang; Zhou, You; Xie, Cuihong; Zhu, Bifeng; Zhu, Huming; Liu, Shupeng; Wang, Wei; Chen, Hongzhuan; Ji, Yonghua

    2015-04-23

    Wasp stings have been arising to be a severe public health problem in China in recent years. However, molecular information about lethal or toxic factors in wasp venom is extremely lacking. In this study, we used two pyrosequencing platforms to analyze the transcriptome of Vespa velutina, the most common wasp species native in China. Besides the substantial amount of transcripts encoding for allergens usually regarded as the major lethal factor of wasp sting, a greater abundance of hemostasis-impairing toxins and neurotoxins in the venom of V. velutina were identified, implying that toxic reactions and allergic effects are envenoming strategy for the dangerous outcomes. The pattern of differentially expressed genes before and after venom extraction clearly indicates that the manifestation of V. velutina stings depends on subtle regulations in the metabolic pathway required for toxin recruitment. This comparative analysis offers timely clues for developing clinical treatments for wasp envenoming in China and around the world.

  12. Venomous snakebite in mountainous terrain: prevention and management.

    PubMed

    Boyd, Jeff J; Agazzi, Giancelso; Svajda, Dario; Morgan, Arthur J; Ferrandis, Silvia; Norris, Robert L

    2007-01-01

    The prevention and management of venomous snakebite in the world's mountains present unique challenges. This paper presents a series of practical, clinically sound recommendations for management of venomous snakebite in a mountain environment. The authors performed an extensive review of current literature using search engines and manual searches. They then fused the abundant knowledge of snakebite with the realities of remote first aid and mountain rescue to develop recommendations. A summary is provided of the world's most troublesome mountain snakes and the mechanisms of toxicity from their bites. Preventive measures are described. Expected symptoms and signs are reviewed in lay and medical terms. A review of currently recommended first-aid measures and advanced medical management for physicians, paramedics, and other clinicians is included. Venomous snakebites in mountainous environments present unique challenges for management. This paper offers practical recommendations for managing such cases and summarizes the approach to first aid and advanced management in 2 algorithms.

  13. Antifungal Activity of Bee Venom and Sweet Bee Venom against Clinically Isolated Candida albicans

    PubMed Central

    Lee, Seung-Bae

    2016-01-01

    Objectives: The purpose of this study was to investigate the antifungal effect of bee venom (BV) and sweet bee venom (SBV) against Candida albicans (C. albicans) clinical isolates. Methods: In this study, BV and SBV were examined for antifungal activities against the Korean Collection for Type Cultures (KCTC) strain and 10 clinical isolates of C. albicans. The disk diffusion method was used to measure the antifungal activity and minimum inhibitory concentration (MIC) assays were performed by using a broth microdilution method. Also, a killing curve assay was conducted to investigate the kinetics of the anti- fungal action. Results: BV and SBV showed antifungal activity against 10 clinical isolates of C. albicans that were cultured from blood and the vagina by using disk diffusion method. The MIC values obtained for clinical isolates by using the broth microdilution method varied from 62.5 μg/ mL to 125 μg/mL for BV and from 15.63 μg/mL to 62.5 μg/mL for SBV. In the killing-curve assay, SBV behaved as amphotericin B, which was used as positive control, did. The antifungal efficacy of SBV was much higher than that of BV. Conclusion: BV and SBV showed antifungal activity against C. albicans clinical strains that were isolated from blood and the vagina. Especially, SBV might be a candidate for a new antifungal agent against C. albicans clinical isolates. PMID:27280049

  14. Preformulation Studies of Bee Venom for the Preparation of Bee Venom-Loaded PLGA Particles.

    PubMed

    Park, Min-Ho; Kim, Ju-Heon; Jeon, Jong-Woon; Park, Jin-Kyu; Lee, Bong-Joo; Suh, Guk-Hyun; Cho, Cheong-Weon

    2015-08-18

    It is known that allergic people was potentially vulnerable to bee venom (BV), which can induce an anaphylactic shock, eventually leading to death. Up until recently, this kind of allergy was treated only by venom immunotherapy (VIT) and its efficacy has been recognized worldwide. This treatment is practiced by subcutaneous injections that gradually increase the doses of the allergen. This is inconvenient for patients due to frequent injections. Poly (D,L-lactide-co-glycolide) (PLGA) has been broadly studied as a carrier for drug delivery systems (DDS) of proteins and peptides. PLGA particles usually induce a sustained release. In this study, the physicochemical properties of BV were examined prior to the preparation of BV-loaded PLGA nanoparticles NPs). The content of melittin, the main component of BV, was 53.3%. When protected from the light BV was stable at 4 °C in distilled water, during 8 weeks. BV-loaded PLGA particles were prepared using dichloromethane as the most suitable organic solvent and two min of ultrasonic emulsification time. This study has characterized the physicochemical properties of BV for the preparation BV-loaded PLGA NPs in order to design and optimize a suitable sustained release system in the future.

  15. Venomic study on cone snails (Conus spp.) from South Africa.

    PubMed

    Kauferstein, Silke; Porth, Christine; Kendel, Yvonne; Wunder, Cora; Nicke, Annette; Kordis, Dusan; Favreau, Philippe; Koua, Dominique; Stöcklin, Reto; Mebs, Dietrich

    2011-01-01

    From six Conus species (Conus coronatus, Conus lividus, Conus mozambicus f. lautus, Conus pictus, Conus sazanka, Conus tinianus) collected off the eastern coast of South Africa the venoms were analyzed using MALDI-TOF mass spectrometry. Between 56 and 151 molecular masses most in a range of 1000 to 2500 Da, were identified. Among the six venoms, between 0 and 27% (C. coronatus versus C. sazanka) of the peptide masses were found to be similar. In a study on venoms from 6 Conus species collected in the Philippines, the percentage of identical masses was between none and 9% only. The venoms from the South African Conus species antagonized the rat neuronal nicotinic acetylcholine receptors (nAChRs) α3β2, α4β2, and α7, except for C. coronatus venom that blocked the α4β2 and α7 nAChRs only. HPLC-fractionation of C. tinianus venom led to the isolation of a peptide that is active on all three receptor subtypes. It consists of 16 amino acid residues cross-linked by two disulfide bridges as revealed by de novo sequencing using tandem mass spectrometry: GGCCSHPACQNNPDYC. Posttranslational modifications include C-terminal amidation and tyrosine sulfation. The new peptide is a member of the α-conotoxin family that are competitive antagonists of nAChRs. Phylogenetic analysis of the 16S RNA from numerous Conus species has clarified the evolutionary position of endemic South African Conus species and provided the first evidence for their close genetic relationships.

  16. SNAKE VENOM POISONING IN SOUTHERN CALIFORNIA

    PubMed Central

    Russell, Findlay E.

    1960-01-01

    The annual incidence of rattlesnake bite in Southern California is approximately 1 per 75,000 population. The case fatality rate is 1.5 per cent. The snakes implicated in the greatest number of injuries are the southern Pacific rattlesnake, the red diamond rattlesnake and the sidewinder. Rattlesnake venom produces deleterious changes in the blood cells, defects in blood coagulation, injury to the intimal linings of vessels, damage to the heart muscle, alterations in the respiratory cycle and, to a lesser extent, changes in neuromuscular conduction. The most frequently observed symptoms and signs following ophidiasis in this area are swelling and edema, pain, ecchymosis, swelling of the regional lymph nodes, weakness, sweating, increased body temperature, faintness, and hemorrhagic vesiculations. First aid treatment consists of immobilization of the affected part, application of a constriction band, incision and suction with subsequent local application of ice packs. Treatment in hospital consists of administration of antivenin, antitetanus agent and antibiotic. Transfusions, oxygen and a corticosteroid may be indicated in some cases. PMID:13744840

  17. 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.

  18. Intraspecific variation in the venoms of the South American rattlesnake (Crotalus durissus terrificus).

    PubMed

    Francischetti, I M; Gombarovits, M E; Valenzuela, J G; Carlini, C R; Guimarães, J A

    2000-08-01

    The venom of eight individual Crotalus durissus terrificus snakes from the State of Minas Gerais, Brazil, in addition to pooled venom from Butantan Institute, were compared. Snakes were captured in distinct locations, some of them 600 km apart: Conselheiro Lafaiete, Entre Rios de Minas, Itauna, Itapecerica, Lavras, Patos de Minas, Paracatu, and Santo Antonio do Amparo. The crude venoms were tested for proteolytic, phospholipase A2, platelet aggregating, and hemagglutinating activities. The venoms were also analyzed by polyacrylamide gel electrophoresis (PAGE) and isoelectric focusing (IEF). Chromatographic patterns of venom proteins on both gel-filtration and anion-exchange chromatographies were also performed. All venoms presented high phospholipase A2 and platelet-aggregating activities, but only minimal hemagglutinating or proteolytic activities were found. Gel-filtration chromatography showed a characteristic profile for most venoms where four main peaks were separated, including the typical ones where convulxin and crotoxin were identified; however, peaks with high amounts of lower molecular weight proteins were found in the venoms from the Santo Antonio do Amparo location and Butantan Institute, characterizing these venoms as crotamine positive. Anion-exchange chromatographies presented a similar protein distribution pattern, although the number of peaks (up to ten) distinguished some venom samples. Consistent with these results, polyacrylamide gels that were silver stained after venom separation by PAGE or IEF presented a similar qualitative band distribution, although a quantitative heterogeneity was detected among venoms. Our results suggest that the variability found in venom components of C. d. terrificus venoms captured in Minas Gerais State may be genetically inherited and/or environmentally induced.

  19. Comparison of Phylogeny, Venom Composition and Neutralization by Antivenom in Diverse Species of Bothrops Complex

    PubMed Central

    Peixoto, Pedro S.; Bernardoni, Juliana L.; Oliveira, Sâmella S.; Portes-Junior, José Antonio; Mourão, Rosa Helena V.; Lima-dos-Santos, Isa; Sano-Martins, Ida S.; Chalkidis, Hipócrates M.; Valente, Richard H.; Moura-da-Silva, Ana M.

    2013-01-01

    In Latin America, Bothrops snakes account for most snake bites in humans, and the recommended treatment is administration of multispecific Bothrops antivenom (SAB – soro antibotrópico). However, Bothrops snakes are very diverse with regard to their venom composition, which raises the issue of which venoms should be used as immunizing antigens for the production of pan-specific Bothrops antivenoms. In this study, we simultaneously compared the composition and reactivity with SAB of venoms collected from six species of snakes, distributed in pairs from three distinct phylogenetic clades: Bothrops, Bothropoides and Rhinocerophis. We also evaluated the neutralization of Bothrops atrox venom, which is the species responsible for most snake bites in the Amazon region, but not included in the immunization antigen mixture used to produce SAB. Using mass spectrometric and chromatographic approaches, we observed a lack of similarity in protein composition between the venoms from closely related snakes and a high similarity between the venoms of phylogenetically more distant snakes, suggesting little connection between taxonomic position and venom composition. P-III snake venom metalloproteinases (SVMPs) are the most antigenic toxins in the venoms of snakes from the Bothrops complex, whereas class P-I SVMPs, snake venom serine proteinases and phospholipases A2 reacted with antibodies in lower levels. Low molecular size toxins, such as disintegrins and bradykinin-potentiating peptides, were poorly antigenic. Toxins from the same protein family showed antigenic cross-reactivity among venoms from different species; SAB was efficient in neutralizing the B. atrox venom major toxins. Thus, we suggest that it is possible to obtain pan-specific effective antivenoms for Bothrops envenomations through immunization with venoms from only a few species of snakes, if these venoms contain protein classes that are representative of all species to which the antivenom is targeted. PMID

  20. 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.

  1. Comparison of phylogeny, venom composition and neutralization by antivenom in diverse species of bothrops complex.

    PubMed

    Sousa, Leijiane F; Nicolau, Carolina A; Peixoto, Pedro S; Bernardoni, Juliana L; Oliveira, Sâmella S; Portes-Junior, José Antonio; Mourão, Rosa Helena V; Lima-dos-Santos, Isa; Sano-Martins, Ida S; Chalkidis, Hipócrates M; Valente, Richard H; Moura-da-Silva, Ana M

    2013-01-01

    In Latin America, Bothrops snakes account for most snake bites in humans, and the recommended treatment is administration of multispecific Bothrops antivenom (SAB--soro antibotrópico). However, Bothrops snakes are very diverse with regard to their venom composition, which raises the issue of which venoms should be used as immunizing antigens for the production of pan-specific Bothrops antivenoms. In this study, we simultaneously compared the composition and reactivity with SAB of venoms collected from six species of snakes, distributed in pairs from three distinct phylogenetic clades: Bothrops, Bothropoides and Rhinocerophis. We also evaluated the neutralization of Bothrops atrox venom, which is the species responsible for most snake bites in the Amazon region, but not included in the immunization antigen mixture used to produce SAB. Using mass spectrometric and chromatographic approaches, we observed a lack of similarity in protein composition between the venoms from closely related snakes and a high similarity between the venoms of phylogenetically more distant snakes, suggesting little connection between taxonomic position and venom composition. P-III snake venom metalloproteinases (SVMPs) are the most antigenic toxins in the venoms of snakes from the Bothrops complex, whereas class P-I SVMPs, snake venom serine proteinases and phospholipases A2 reacted with antibodies in lower levels. Low molecular size toxins, such as disintegrins and bradykinin-potentiating peptides, were poorly antigenic. Toxins from the same protein family showed antigenic cross-reactivity among venoms from different species; SAB was efficient in neutralizing the B. atrox venom major toxins. Thus, we suggest that it is possible to obtain pan-specific effective antivenoms for Bothrops envenomations through immunization with venoms from only a few species of snakes, if these venoms contain protein classes that are representative of all species to which the antivenom is targeted.

  2. Sex Differences in Defensive Behavior and Venom of The Striped Bark Scorpion Centruroides vittatus (Scorpiones: Buthidae).

    PubMed

    Miller, D W; Jones, A D; Goldston, J S; Rowe, M P; Rowe, A H

    2016-11-01

    Studies of venom variability have advanced from describing the mechanisms of action and relative potency of medically important toxins to understanding the ecological and evolutionary causes of the variability itself. While most studies have focused on differences in venoms among taxa, populations, or age-classes, there may be intersexual effects as well. Striped bark scorpions (Centruroides vittatus) provide a good model for examining sex differences in venom composition and efficacy, as this species exhibits dramatic sexual dimorphism in both size and defensive behavior; when threatened by an enemy, larger, slower females stand and fight while smaller, fleeter males prefer to run. We here add evidence suggesting that male and female C. vittatus indeed have different defensive propensities; when threatened via an electrical stimulus, females were more likely to sting than were males. We reasoned that intersexual differences in defensive phenotypes would select for venoms with different functions in the two sexes; female venoms should be effective at predator deterrence, whereas male venoms, less utilized defensively, might be better suited to capturing prey or courting females. This rationale led to our predictions that females would inject more venom and/or possess more painful venom than males. We were wrong. While females do inject more venom than males in a defensive sting, females are also larger; when adjusted for body size, male and female C. vittatus commit equal masses of venom in a sting to a potential enemy. Additionally, house mice (Mus musculus) find an injection of male venom more irritating than an equal amount of female venom, likely because male venom contains more of the toxins that induce pain. Taken together, our results suggest that identifying the ultimate causes of venom variability will, as we move beyond adaptive storytelling, be hard-won.

  3. 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

  4. Venom Down Under: Dynamic Evolution of Australian Elapid Snake Toxins

    PubMed Central

    Jackson, Timothy N. W.; Sunagar, Kartik; Undheim, Eivind A. B.; Koludarov, Ivan; Chan, Angelo H. C.; Sanders, Kate; Ali, Syed A.; Hendrikx, Iwan; Dunstan, Nathan; Fry, Bryan G.

    2013-01-01

    Despite the unparalleled diversity of venomous snakes in Australia, research has concentrated on a handful of medically significant species and even of these very few toxins have been fully sequenced. In this study, venom gland transcriptomes were sequenced from eleven species of small Australian elapid snakes, from eleven genera, spanning a broad phylogenetic range. The particularly large number of sequences obtained for three-finger toxin (3FTx) peptides allowed for robust reconstructions of their dynamic molecular evolutionary histories. We demonstrated that each species preferentially favoured different types of α-neurotoxic 3FTx, probably as a result of differing feeding ecologies. The three forms of α-neurotoxin [Type I (also known as (aka): short-chain), Type II (aka: long-chain) and Type III] not only adopted differential rates of evolution, but have also conserved a diversity of residues, presumably to potentiate prey-specific toxicity. Despite these differences, the different α-neurotoxin types were shown to accumulate mutations in similar regions of the protein, largely in the loops and structurally unimportant regions, highlighting the significant role of focal mutagenesis. We theorize that this phenomenon not only affects toxin potency or specificity, but also generates necessary variation for preventing/delaying prey animals from acquiring venom-resistance. This study also recovered the first full-length sequences for multimeric phospholipase A2 (PLA2) ‘taipoxin/paradoxin’ subunits from non-Oxyuranus species, confirming the early recruitment of this extremely potent neurotoxin complex to the venom arsenal of Australian elapid snakes. We also recovered the first natriuretic peptides from an elapid that lack the derived C-terminal tail and resemble the plesiotypic form (ancestral character state) found in viper venoms. This provides supporting evidence for a single early recruitment of natriuretic peptides into snake venoms. Novel forms of kunitz

  5. Computational Studies of Venom Peptides Targeting Potassium Channels

    PubMed Central

    Chen, Rong; Chung, Shin-Ho

    2015-01-01

    Small peptides isolated from the venom of animals are potential scaffolds for ion channel drug discovery. This review article mainly focuses on the computational studies that have advanced our understanding of how various toxins interfere with the function of K+ channels. We introduce the computational tools available for the study of toxin-channel interactions. We then discuss how these computational tools have been fruitfully applied to elucidate the mechanisms of action of a wide range of venom peptides from scorpions, spiders, and sea anemone. PMID:26633507

  6. Animal venoms/toxins and the complement system.

    PubMed

    Tambourgi, Denise V; van den Berg, Carmen W

    2014-10-01

    Nature is a wealthy source of agents that have been shown to be beneficial to human health, but nature is also a rich source of potential dangerous health damaging compounds. This review will summarise and discuss the agents from the animal kingdom that have been shown to interact with the human complement (C) system. Most of these agents are toxins found in animal venoms and animal secretions. In addition to the mechanism of action of these toxins, their contribution to the field of complement, their role in human pathology and the potential benefit to the venomous animal itself will be discussed. Potential therapeutic applications will also be discussed.

  7. Venom down under: dynamic evolution of Australian elapid snake toxins.

    PubMed

    Jackson, Timothy N W; Sunagar, Kartik; Undheim, Eivind A B; Koludarov, Ivan; Chan, Angelo H C; Sanders, Kate; Ali, Syed A; Hendrikx, Iwan; Dunstan, Nathan; Fry, Bryan G

    2013-12-18

    Despite the unparalleled diversity of venomous snakes in Australia, research has concentrated on a handful of medically significant species and even of these very few toxins have been fully sequenced. In this study, venom gland transcriptomes were sequenced from eleven species of small Australian elapid snakes, from eleven genera, spanning a broad phylogenetic range. The particularly large number of sequences obtained for three-finger toxin (3FTx) peptides allowed for robust reconstructions of their dynamic molecular evolutionary histories. We demonstrated that each species preferentially favoured different types of α-neurotoxic 3FTx, probably as a result of differing feeding ecologies. The three forms of α-neurotoxin [Type I (also known as (aka): short-chain), Type II (aka: long-chain) and Type III] not only adopted differential rates of evolution, but have also conserved a diversity of residues, presumably to potentiate prey-specific toxicity. Despite these differences, the different α-neurotoxin types were shown to accumulate mutations in similar regions of the protein, largely in the loops and structurally unimportant regions, highlighting the significant role of focal mutagenesis. We theorize that this phenomenon not only affects toxin potency or specificity, but also generates necessary variation for preventing/delaying prey animals from acquiring venom-resistance. This study also recovered the first full-length sequences for multimeric phospholipase A2 (PLA2) 'taipoxin/paradoxin' subunits from non-Oxyuranus species, confirming the early recruitment of this extremely potent neurotoxin complex to the venom arsenal of Australian elapid snakes. We also recovered the first natriuretic peptides from an elapid that lack the derived C-terminal tail and resemble the plesiotypic form (ancestral character state) found in viper venoms. This provides supporting evidence for a single early recruitment of natriuretic peptides into snake venoms. Novel forms of kunitz and

  8. Testing the 'toxin hypothesis of allergy': mast cells, IgE, and innate and acquired immune responses to venoms.

    PubMed

    Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J

    2015-10-01

    Work in mice indicates that innate functions of mast cells, particularly degradation of venom toxins by mast cell-derived proteases, can enhance resistance to certain arthropod or reptile venoms. Recent reports indicate that acquired Th2 immune responses associated with the production of IgE antibodies, induced by Russell's viper venom or honeybee venom, or by a component of honeybee venom, bee venom phospholipase 2 (bvPLA2), can increase the resistance of mice to challenge with potentially lethal doses of either of the venoms or bvPLA2. These findings support the conclusion that, in contrast to the detrimental effects associated with allergic type 2 (Th2) immune responses, mast cells and IgE-dependent immune responses to venoms can contribute to innate and adaptive resistance to venom-induced pathology and mortality.

  9. Testing the "toxin hypothesis of allergy": Mast cells, IgE, and innate and acquired immune responses to venoms*

    PubMed Central

    Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J.

    2015-01-01

    Summary Work in mice indicates that innate functions of mast cells, particularly degradation of venom toxins by mast cell-derived proteases, can enhance resistance to certain arthropod or reptile venoms. Recent reports indicate that acquired Th2 immune responses associated with the production of IgE antibodies, induced by Russell’s viper venom or honeybee venom, or by a component of honeybee venom, bee venom phospholipase 2 (bvPLA2), can increase the resistance of mice to challenge with potentially lethal doses of either of the venoms or bvPLA2. These findings support the conclusion that, in contrast to the detrimental effects associated with allergic Th2 immune responses, mast cells and IgE-dependent immune responses to venoms can contribute to innate and adaptive resistance to venom-induced pathology and mortality. PMID:26210895

  10. Venom ophthalmia caused by venoms of spitting elapid and other snakes: Report of ten cases with review of epidemiology, clinical features, pathophysiology and management.

    PubMed

    Chu, Edward R; Weinstein, Scott A; White, Julian; Warrell, David A

    2010-09-01

    Venom ophthalmia caused by venoms of spitting elapid and other snakes: report of ten cases with review of epidemiology, clinical features, pathophysiology and management. Chu, ER, Weinstein, SA, White, J and Warrell, DA. Toxicon XX:xxx-xxx. We present ten cases of ocular injury following instillation into the eye of snake venoms or toxins by spitting elapids and other snakes. The natural history of spitting elapids and the toxinology of their venoms are reviewed together with the medical effects and management of venom ophthalmia in humans and domestic animals including both direct and allergic effects of venoms. Although the clinical features and management of envenoming following bites by spitting elapids (genera Naja and Hemachatus) are well documented, these snakes are also capable of "spraying" venom towards the eyes of predators, a defensive strategy that causes painful and potentially blinding ocular envenoming (venom ophthalmia). Little attention has been given to the detailed clinical description, clinical evolution and efficacy of treatment of venom ophthalmia and no clear management guidelines have been formulated. Knowledge of the pathophysiology of ocular envenoming is based largely on animal studies and a limited body of clinical information. A few cases of ocular exposure to venoms from crotaline viperids have also been described. Venom ophthalmia often presents with pain, hyperemia, blepharitis, blepharospasm and corneal erosions. Delay or lack of treatment may result in corneal opacity, hypopyon and/or blindness. When venom is "spat" into the eye, cranial nerve VII may be affected by local spread of venom but systemic envenoming has not been documented in human patients. Management of venom ophthalmia consists of: 1) urgent decontamination by copious irrigation 2) analgesia by vasoconstrictors with weak mydriatic activity (e.g. epinephrine) and limited topical administration of local anesthetics (e.g. tetracaine) 3) exclusion of corneal abrasions

  11. Venom lethality and diet: differential responses of natural prey and model organisms to the venom of the saw-scaled vipers (Echis).

    PubMed

    Richards, D P; Barlow, A; Wüster, W

    2012-01-01

    The composition of snake venoms shows a high degree of variation at all taxonomic levels, and natural selection for diet has been implicated as a potential cause. Saw-scaled vipers (Echis) provide a good model for studying this phenomenon. The venoms of arthropod feeding species of Echis are significantly more toxic to natural scorpion prey than those of species which feed predominantly upon vertebrate prey. Although testing venom activity on natural prey is important for our understanding of the evolution of venom, natural prey species are often difficult to obtain in sufficient numbers for toxinological work. In order to test the viability of using cheaper and more easily available model organisms for toxicity assessments in evolutionary research, and the extent to which toxicity of arthropod-eating Echis venoms is increased to arthropods in general or targeted to certain groups, we conducted median lethal dosage (LD(50)) and time to death trials using the desert locust (Schistocerca gregaria) as a model arthropod, rarely consumed by wild Echis. The venoms of arthropod specialist Echis were found to be significantly more toxic to locusts than the venom of a vertebrate feeding outgroup (Bitis arietans), and one arthropod specialist venom was found to be more toxic than those species which feed upon arthropods infrequently or not at all. The venoms of arthropod specialists were also found to cause death and incapacitation faster than the vertebrate feeding outgroup. Despite some similarity of trends, there are considerable differences between the response of natural prey (scorpions) and a model arthropod (locust) to the venoms of Echis species. This suggests that when possible, natural prey rather than convenient model organisms should be used to gain an understanding of the functional significance of variation in venom composition in snakes.

  12. An isoflavone from Dipteryx alata Vogel is active against the in vitro neuromuscular paralysis of Bothrops jararacussu snake venom and bothropstoxin I, and prevents venom-induced myonecrosis.

    PubMed

    Ferraz, Miriéle C; Yoshida, Edson H; Tavares, Renata V S; Cogo, José C; Cintra, Adélia C O; Dal Belo, Cháriston A; Franco, Luiz M; dos Santos, Márcio G; Resende, Flávia A; Varanda, Eliana A; Hyslop, Stephen; Puebla, Pilar; San Feliciano, Arturo; Oshima-Franco, Yoko

    2014-05-06

    Snakebite is a neglected disease and serious health problem in Brazil, with most bites being caused by snakes of the genus Bothrops. Although serum therapy is the primary treatment for systemic envenomation, it is generally ineffective in neutralizing the local effects of these venoms. In this work, we examined the ability of 7,8,3'-trihydroxy-4'-methoxyisoflavone (TM), an isoflavone from Dipteryx alata, to neutralize the neurotoxicity (in mouse phrenic nerve-diaphragm preparations) and myotoxicity (assessed by light microscopy) of Bothrops jararacussu snake venom in vitro. The toxicity of TM was assessed using the Salmonella microsome assay (Ames test). Incubation with TM alone (200 μg/mL) did not alter the muscle twitch tension whereas incubation with venom (40 μg/mL) caused irreversible paralysis. Preincubation of TM (200 μg/mL) with venom attenuated the venom-induced neuromuscular blockade by 84% ± 5% (mean ± SEM; n = 4). The neuromuscular blockade caused by bothropstoxin-I (BthTX-I), the major myotoxic PLA2 of this venom, was also attenuated by TM. Histological analysis of diaphragm muscle incubated with TM showed that most fibers were preserved (only 9.2% ± 1.7% were damaged; n = 4) compared to venom alone (50.3% ± 5.4% of fibers damaged; n = 3), and preincubation of TM with venom significantly attenuated the venom-induced damage (only 17% ± 3.4% of fibers damaged; n = 3; p < 0.05 compared to venom alone). TM showed no mutagenicity in the Ames test using Salmonella strains TA98 and TA97a with (+S9) and without (-S9) metabolic activation. These findings indicate that TM is a potentially useful compound for antagonizing the neuromuscular effects (neurotoxicity and myotoxicity) of B. jararacussu venom.

  13. ADP is a vasodilator component from Lasiodora sp. mygalomorph spider venom.

    PubMed

    Horta, C C; Rezende, B A; Oliveira-Mendes, B B R; Carmo, A O; Capettini, L S A; Silva, J F; Gomes, M T; Chávez-Olórtegui, C; Bravo, C E S; Lemos, V S; Kalapothakis, E

    2013-09-01

    Members of the spider genus Lasiodora are widely distributed in Brazil, where they are commonly known as caranguejeiras. Lasiodora spider venom is slightly harmful to humans. The bite of this spider causes local pain, edema and erythema. However, Lasiodora sp. spider venom may be a source of important pharmacological tools. Our research group has described previously that Lasiodora sp. venom produces bradycardia in the isolated rat heart. In the present work, we sought to evaluate the vascular effect of Lasiodora sp. venom and to isolate the vasoactive compounds from the venom. The results showed that Lasiodora spider venom induced a concentration-dependent vasodilation in rat aortic rings, which was dependent on the presence of a functional endothelium and abolished by the nitric oxide synthase (NOS) inhibitor L-NAME. Western blot experiments revealed that the venom also increased endothelial NOS function by increasing phosphorylation of the Ser¹¹⁷⁷ residue. Assay-directed fractionation isolated a vasoactive fraction from Lasiodora sp. venom. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) assays identified a mixture of two compounds: adenosine diphosphate (ADP, approximately 90%) and adenosine monophosphate (AMP, approximately 10%). The vasodilator effects of Lasiodora sp. whole venom, as well as ADP, were significantly inhibited by suramin, which is a purinergic P2-receptor antagonist. Therefore, the results of the present work indicate that ADP is a main vasodilator component of Lasiodora sp. spider venom.

  14. Hormone-like peptides in the venoms of marine cone snails

    PubMed Central

    Robinson, Samuel D.; Li, Qing; Bandyopadhyay, Pradip K.; Gajewiak, Joanna; Yandell, Mark; Papenfuss, Anthony T.; Purcell, Anthony W.; Norton, Raymond S.; Safavi-Hemami, Helena

    2015-01-01

    The venoms of cone snails (genus Conus) are remarkably complex, consisting of hundreds of typically short, disulfide-rich peptides termed conotoxins. These peptides have diverse pharmacological targets, with injection of venom eliciting a range of physiological responses, including sedation, paralysis and sensory overload. Most conotoxins target the prey’s nervous system but evidence of venom peptides targeting neuroendocrine processes is emerging. Examples include vasopressin, RFamide neuropeptides and recently also insulin. To investigate the diversity of hormone/neuropeptide-like molecules in the venoms of cone snails we systematically mined the venom gland transcriptomes of several cone snail species and examined secreted venom peptides in dissected and injected venom of the Australian cone snail Conus victoriae. Using this approach we identified several novel hormone/neuropeptide-like toxins, including peptides similar to the bee brain hormone prohormone-4, the mollusc ganglia neuropeptide elevenin, and thyrostimulin, a member of the glycoprotein hormone family, and confirmed the presence of insulin. We confirmed that at least two of these peptides are not only expressed in the venom gland but also form part of the injected venom cocktail, unambiguously demonstrating their role in envenomation. Our findings suggest that hormone/neuropeptide-like toxins are a diverse and integral part of the complex envenomation strategy of Conus. Exploration of this group of venom components offers an exciting new avenue for the discovery of novel pharmacological tools and drug candidates, complementary to conotoxins. PMID:26301480

  15. Antivenom to the venom of the male Sydney funnel-web spider Atrax robustus: preliminary report.

    PubMed

    Sutherland, S K

    1980-10-18

    A purified rabbit IgG (antivenom) has been isolated from rabbits immunized with male Atrax robustus venom. This preparation has been shown to neutralize in vitro, male venom in a ratio of 97 microgram of IgG to 1 microgram of male venom. The venoms of a number of other members of the Atrax genus are also neutralized in vitro by this antivenom. Of particular importance is the fact that the venom of the extremely dangerous female A. formidabilis is neutralized. A serum harvest of 55 mL from an immunized rabbit yielded a total of 1.1869 g of immune IgG using the Protein A-Sepharose procedure. This quantity is sufficient antivenom to neutralize in vitro the average yield of 67 spiders. These findings suggest the preparation of an antivenom for human use is now feasible. The antivenom was shown to effectively neutralize venom in monkeys either when it was premixed with the venom before injection or when it was injected separately 10 minutes after injection of venom. This is the first time in-vitro and in-vivo neutralization of this venom has been demonstrated in the monkey. In other studies, a range of non-immunized animal sera was shown to have no inherent ability to neutralize male A. robustus venom in vitro.

  16. Bee Venom Phospholipase A2: Yesterday’s Enemy Becomes Today’s Friend

    PubMed Central

    Lee, Gihyun; Bae, Hyunsu

    2016-01-01

    Bee venom therapy has been used to treat immune-related diseases such as arthritis for a long time. Recently, it has revealed that group III secretory phospholipase A2 from bee venom (bee venom group III sPLA2) has in vitro and in vivo immunomodulatory effects. A growing number of reports have demonstrated the therapeutic effects of bee venom group III sPLA2. Notably, new experimental data have shown protective immune responses of bee venom group III sPLA2 against a wide range of diseases including asthma, Parkinson’s disease, and drug-induced organ inflammation. It is critical to evaluate the beneficial and adverse effects of bee venom group III sPLA2 because this enzyme is known to be the major allergen of bee venom that can cause anaphylactic shock. For many decades, efforts have been made to avoid its adverse effects. At high concentrations, exposure to bee venom group III sPLA2 can result in damage to cellular membranes and necrotic cell death. In this review, we summarized the current knowledge about the therapeutic effects of bee venom group III sPLA2 on several immunological diseases and described the detailed mechanisms of bee venom group III sPLA2 in regulating various immune responses and physiopathological changes. PMID:26907347

  17. Hormone-like peptides in the venoms of marine cone snails.

    PubMed

    Robinson, Samuel D; Li, Qing; Bandyopadhyay, Pradip K; Gajewiak, Joanna; Yandell, Mark; Papenfuss, Anthony T; Purcell, Anthony W; Norton, Raymond S; Safavi-Hemami, Helena

    2017-04-01

    The venoms of cone snails (genus Conus) are remarkably complex, consisting of hundreds of typically short, disulfide-rich peptides termed conotoxins. These peptides have diverse pharmacological targets, with injection of venom eliciting a range of physiological responses, including sedation, paralysis and sensory overload. Most conotoxins target the prey's nervous system but evidence of venom peptides targeting neuroendocrine processes is emerging. Examples include vasopressin, RFamide neuropeptides and recently also insulin. To investigate the diversity of hormone/neuropeptide-like molecules in the venoms of cone snails we systematically mined the venom gland transcriptomes of several cone snail species and examined secreted venom peptides in dissected and injected venom of the Australian cone snail Conus victoriae. Using this approach we identified several novel hormone/neuropeptide-like toxins, including peptides similar to the bee brain hormone prohormone-4, the mollusc ganglia neuropeptide elevenin, and thyrostimulin, a member of the glycoprotein hormone family, and confirmed the presence of insulin. We confirmed that at least two of these peptides are not only expressed in the venom gland but also form part of the injected venom cocktail, unambiguously demonstrating their role in envenomation. Our findings suggest that hormone/neuropeptide-like toxins are a diverse and integral part of the complex envenomation strategy of Conus. Exploration of this group of venom components offers an exciting new avenue for the discovery of novel pharmacological tools and drug candidates, complementary to conotoxins.

  18. Recruitment and diversification of an ecdysozoan family of neuropeptide hormones for black widow spider venom expression

    PubMed Central

    McCowan, Caryn; Garb, Jessica E.

    2014-01-01

    Venoms have attracted enormous attention because of their potent physiological effects and dynamic evolution, including the convergent recruitment of homologous genes for venom expression. Here we provide novel evidence for the recruitment of genes from the Crustacean Hyperglycemic Hormone (CHH) and arthropod Ion Transport Peptide (ITP) superfamily for venom expression in black widow spiders. We characterized latrodectin peptides from venom gland cDNAs from the Western black widow spider (Latrodectus hesperus), the brown widow (L. geometricus) and cupboard spider (Steatoda grossa). Phylogenetic analyses of these sequences with homologs from other spider, scorpion and wasp venom cDNAs, as well as CHH/ITP neuropeptides, show latrodectins as derived members of the CHH/ITP superfamily. These analyses suggest that CHH/ITP homologs are more widespread in spider venoms, and were recruited for venom expression in two additional arthropod lineages. We also found that the latrodectin 2 gene and nearly all CHH/ITP genes include a phase 2 intron in the same position, supporting latrodectin’s placement within the CHH/ITP superfamily. Evolutionary analyses of latrodectins suggest episodes of positive selection along some sequence lineages, and positive and purifying selection on specific codons, supporting its functional importance in widow venom. We consider how this improved understanding of latrodectin evolution informs functional hypotheses regarding its role in black widow venom as well as its potential convergent recruitment for venom expression across arthropods. PMID:24316130

  19. Adaptive evolution of the venom-targeted vWF protein in opossums that eat pitvipers.

    PubMed

    Jansa, Sharon A; Voss, Robert S

    2011-01-01

    The rapid evolution of venom toxin genes is often explained as the result of a biochemical arms race between venomous animals and their prey. However, it is not clear that an arms race analogy is appropriate in this context because there is no published evidence for rapid evolution in genes that might confer toxin resistance among routinely envenomed species. Here we report such evidence from an unusual predator-prey relationship between opossums (Marsupialia: Didelphidae) and pitvipers (Serpentes: Crotalinae). In particular, we found high ratios of replacement to silent substitutions in the gene encoding von Willebrand Factor (vWF), a venom-targeted hemostatic blood protein, in a clade of opossums known to eat pitvipers and to be resistant to their hemorrhagic venom. Observed amino-acid substitutions in venom-resistant opossums include changes in net charge and hydrophobicity that are hypothesized to weaken the bond between vWF and one of its toxic snake-venom ligands, the C-type lectin-like protein botrocetin. Our results provide the first example of rapid adaptive evolution in any venom-targeted molecule, and they support the notion that an evolutionary arms race might be driving the rapid evolution of snake venoms. However, in the arms race implied by our results, venomous snakes are prey, and their venom has a correspondingly defensive function in addition to its usual trophic role.

  20. Preparation and characterization of bee venom-loaded PLGA particles for sustained release.

    PubMed

    Park, Min-Ho; Jun, Hye-Suk; Jeon, Jong-Woon; Park, Jin-Kyu; Lee, Bong-Joo; Suh, Guk-Hyun; Park, Jeong-Sook; Cho, Cheong-Weon

    2016-12-14

    Bee venom-loaded poly(lactic-co-glycolic acid) (PLGA) particles were prepared by double emulsion-solvent evaporation, and characterized for a sustained-release system. Factors such as the type of organic solvent, the amount of bee venom and PLGA, the type of PLGA, the type of polyvinyl alcohol, and the emulsification method were considered. Physicochemical properties, including the encapsulation efficiency, drug loading, particle size, zeta-potential and surface morphology were examined by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The size of the bee venom-loaded PLGA particles was 500 nm (measured using sonication). Zeta-potentials of the bee venom-loaded PLGA particles were negative owing to the PLGA. FT-IR results demonstrated that the bee venom was completely encapsulated in the PLGA particles, indicated by the disappearance of the amine and amide peaks. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated that the bee venom in the bee venom-loaded PLGA particles was intact. In vitro release of the bee venom from the bee venom-loaded PLGA particles showed a sustained-release profile over 1 month. Bee venom-loaded PLGA particles can help improve patients' quality of life by reducing the number of injections required.

  1. Hydrolase activity in the venom of the pupal endoparasitic wasp, Pimpla hypochondriaca.

    PubMed

    Dani, M P; Edwards, J P; Richards, E H

    2005-07-01

    Venom from the pupal endoparasitoid, Pimpla hypochondriaca has previously been shown to contain a mixture of biologically active molecules. Currently, P. hypochondriaca venom was examined for the presence of hydrolase activity. Six hydrolases were consistently detected using the API ZYM semiquantitative colourimetric kit. The main hydrolases detected were; acid phosphatase, beta-glucosidase, esterase, beta-galactosidase, esterase lipase, and lipase. The most rapid and intense colour reaction was detected for acid phosphatase. The pH optimum and the specific activity of venom acid phosphatase was determined using p-nitrophenol phosphate as a substrate and were 4.8 and 0.47 nmol p-nitrophenol/min/microg of venom protein, respectively. The acid phosphatase activity was inhibited in a dose dependent manner by sodium fluoride (IC(50) 4.2 x 10(-4) M), and by cocktail inhibitor 2 (CI 2). P. hypochondriaca venom has previously been shown to display potent cytotoxic activity towards Lacanobia oleracea haemocytes maintained in vitro. The contribution of acid phosphatase in venom to this cytotoxic activity was investigated by titrating venom against CI 2 prior to the addition of L. oleracea haemocytes. The results suggest that, despite the relatively high levels of acid phosphatase activity in venom, venom acid phosphatase plays no role in the antihaemocytic activity of P. hypochondriaca venom in vitro.

  2. Venom variation in hemostasis of the southern Pacific rattlesnake (Crotalus oreganus helleri): isolation of hellerase.

    PubMed

    Salazar, Ana Maria; Guerrero, Belsy; Cantu, Bruno; Cantu, Esteban; Rodríguez-Acosta, Alexis; Pérez, John C; Galán, Jacob A; Tao, Andy; Sánchez, Elda E

    2009-04-01

    Envenomations by the southern Pacific rattlesnake (Crotalus oreganus helleri) are the most common snakebite accidents in southern California. Intraspecies venom variation may lead to unresponsiveness to antivenom therapy. Even in a known species, venom toxins are recognized as diverse in conformity with interpopulational, seasonal, ontogenetic and individual factors. Five venoms of individual C. oreganus helleri located in Riverside and San Bernardino counties of southern California were studied for their variation in their hemostatic activity. The results demonstrated that Riverside 2 and San Bernardino 1 venoms presented the highest lethal activity without hemorrhagic activity. In contrast, San Bernardino 2 and 3 venoms had the highest hemorrhagic and fibrinolytic activities with low lethal and coagulant activities. Riverside 1, Riverside 2 and San Bernardino 1 venoms presented a significant thrombin-like activity. San Bernardino 2 and 3 venoms presented an insignificant thrombin-like activity. In relation to the fibrinolytic activity, San Bernardino 3 venom was the most active on fibrin plates, which was in turn neutralized by metal chelating inhibitors. These results demonstrate the differences amongst C. oreganus helleri venoms from close localities. A metalloproteinase, hellerase, was purified by anionic and cationic exchange chromatographies from San Bernardino 3 venom. Hellerase exhibited the ability to break fibrin clots in vitro, which can be of biomedically importance in the treatment of heart attacks and strokes.

  3. Rock squirrel (Spermophilus variegatus) blood sera affects proteolytic and hemolytic activities of rattlesnake venoms.

    PubMed

    Biardi, James E; Coss, Richard G

    2011-02-01

    Rock squirrels (Spermophilus variegatus) from two sites in south central New Mexico, where prairie (Crotalus viridis viridis) and western diamondback (Crotalus atrox) rattlesnakes are common predators, were assayed for inhibition of rattlesnake venom digestive and hemostatic activities. At statistically significant levels rock squirrel blood sera reduced the metalloprotease and hemolytic activity of venoms from C. v. viridis and C. atrox more than venom from an allopatric snake species, the northern Pacific rattlesnake (Crotalus oreganus). In contrast, general proteolytic activity of venom from C. oreganus was inhibited more by S. variegatus serum defenses than activity of venom from sympatric snakes. For all three venoms, incubation with squirrel sera increased the level of fibrinolysis over venom-only treatments. These results suggest that rock squirrels (S. variegatus) can defend against metalloproteases and other proteases after envenomation from at least two of five rattlesnake predators they might encounter. However, there were statistically significant differences between general proteolytic activity and fibrinolytic activity of C. v. viridis and C. atrox venom, suggesting that rock squirrels might be differentially vulnerable to these two predators. The hypothesis that prey resistance influences snake venom evolution in a predator-prey arms race is given further support by the previously cryptic variation in venoms detected when assayed against prey defenses.

  4. [Effects of venom from Sclerodermus sichuanensis Xiao on pupa of Tenebrio molitor].

    PubMed

    Zhuo, Zhi-Hang; Yang, Wei; Qin, Huan; Yang, Chun-Ping; Yang, Hua; Xu, Dan-Ping

    2013-11-01

    To explore the regulatory mechanisms of parasitism of Sclerodermus sichuanensis on Tenebrio molitor, the methods of natural parasitism and venom injection were adopted to investigate the effects of the venom from S. sichuanensis on the pupa of T. molitor in the parasitic process. Under venom injection, the paralytic degree of the pupa had a positive correlation with the concentration of injected venom, and the number of recovered pupa had a negative correlation with the injected venom concentration. The T. molitor pupa was in slight and reversible paralysis when injected with 0.01 VRE (venom reservoir equivalent) of venom, and in non-reversible and complete paralysis when 0.2 VRE was injected. The pupa died massively and appeared a wide range of melanization when injected with soil bacterial suspension alone, but the melanization delayed and the mortality declined significantly when the mixed liquor of bacterium and venom was injected. The bacteriostasis of the venom on Staphylococcus aureus was significantly stronger than that on Escherichia coli. Within a definite range of temperature, the paralytic activity decreased significantly with increasing temperature, the bacteriostasis on S. aureus increased significantly, while that on E. coli was opposite. This study showed that the venom from S. sichuanensis had the effects of paralysis, bacteriostasis, inhibiting exuviations, and delaying melanization.

  5. Comparative analysis of proteases in the injected and dissected venom of cone snail species.

    PubMed

    Möller, Carolina; Vanderweit, Nicole; Bubis, José; Marí, Frank

    2013-04-01

    The venom of cone snails has been the subject of intense studies because it contains small neuroactive peptides of therapeutic value. However, much less is known about their larger proteins counterparts and their role in prey envenomation. Here, we analyzed the proteolytic enzymes in the injected venom of Conus purpurascens and Conus ermineus (piscivorous), and the dissected venom of C. purpurascens, Conus marmoreus (molluscivorous) and Conus virgo (vermivorous). Zymograms show that all venom samples displayed proteolytic activity on gelatin. However, the electrophoresis patterns and sizes of the proteases varied considerably among these four species. The protease distribution also varied dramatically between the injected and dissected venom of C. purpurascens. Protease inhibitors demonstrated that serine and metalloproteases are responsible for the gelatinolytic activity. We found fibrinogenolytic activity in the injected venom of C. ermineus suggesting that this venom might have effects on the hemostatic system of the prey. Remarkable differences in protein and protease expression were found in different sections of the venom duct, indicating that these components are related to the storage granules and that they participate in venom biosynthesis. Consequently, different conoproteases play major roles in venom processing and prey envenomation.

  6. Restriction and Recruitment—Gene Duplication and the Origin and Evolution of Snake Venom Toxins

    PubMed Central

    Hargreaves, Adam D.; Swain, Martin T.; Hegarty, Matthew J.; Logan, Darren W.; Mulley, John F.

    2014-01-01

    Snake venom has been hypothesized to have originated and diversified through a process that involves duplication of genes encoding body proteins with subsequent recruitment of the copy to the venom gland, where natural selection acts to develop or increase toxicity. However, gene duplication is known to be a rare event in vertebrate genomes, and the recruitment of duplicated genes to a novel expression domain (neofunctionalization) is an even rarer process that requires the evolution of novel combinations of transcription factor binding sites in upstream regulatory regions. Therefore, although this hypothesis concerning the evolution of snake venom is very unlikely and should be regarded with caution, it is nonetheless often assumed to be established fact, hindering research into the true origins of snake venom toxins. To critically evaluate this hypothesis, we have generated transcriptomic data for body tissues and salivary and venom glands from five species of venomous and nonvenomous reptiles. Our comparative transcriptomic analysis of these data reveals that snake venom does not evolve through the hypothesized process of duplication and recruitment of genes encoding body proteins. Indeed, our results show that many proposed venom toxins are in fact expressed in a wide variety of body tissues, including the salivary gland of nonvenomous reptiles and that these genes have therefore been restricted to the venom gland following duplication, not recruited. Thus, snake venom evolves through the duplication and subfunctionalization of genes encoding existing salivary proteins. These results highlight the danger of the elegant and intuitive “just-so story” in evolutionary biology. PMID:25079342

  7. Comparisons of Protein and Peptide Complexity in Poneroid and Formicoid Ant Venoms.

    PubMed

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

    2016-09-02

    Animal venom peptides are currently being developed as novel drugs and bioinsecticides. Because ants use venoms for defense and predation, venomous ants represent an untapped source of potential bioactive toxins. This study compared the protein and peptide components of the poneroid ants Neoponera commutata, Neoponera apicalis, and Odontomachus hastatus and the formicoid ants Ectatomma tuberculatum, Ectatomma brunneum, and Myrmecia gulosa. 1D and 2D PAGE revealed venom proteins in the mass range <10 to >250 kDa. NanoLC-ESI-QTOF MS/MS analysis of tryptic peptides revealed the presence of common venom proteins and also many undescribed proteins. RP-HPLC separation followed by MALDI-TOF MS of the venom peptides also revealed considerable heterogeneity. It was found that the venoms contained between 144 and 1032 peptides with 5-95% of peptides in the ranges 1-4 and 1-8 kDa for poneroid and formicoid ants, respectively. By employing the reducing MALDI matrix 1,5-diaminonapthalene, up to 28 disulfide-bonded peptides were also identified in each of the venoms. In particular, the mass range of peptides from poneroid ants is lower than peptides from other venoms, indicating possible novel structures and pharmacologies. These results indicate that ant venoms represent an enormous, untapped source of novel therapeutic and bioinsecticide leads.

  8. Restriction and recruitment-gene duplication and the origin and evolution of snake venom toxins.

    PubMed

    Hargreaves, Adam D; Swain, Martin T; Hegarty, Matthew J; Logan, Darren W; Mulley, John F

    2014-08-01

    Snake venom has been hypothesized to have originated and diversified through a process that involves duplication of genes encoding body proteins with subsequent recruitment of the copy to the venom gland, where natural selection acts to develop or increase toxicity. However, gene duplication is known to be a rare event in vertebrate genomes, and the recruitment of duplicated genes to a novel expression domain (neofunctionalization) is an even rarer process that requires the evolution of novel combinations of transcription factor binding sites in upstream regulatory regions. Therefore, although this hypothesis concerning the evolution of snake venom is very unlikely and should be regarded with caution, it is nonetheless often assumed to be established fact, hindering research into the true origins of snake venom toxins. To critically evaluate this hypothesis, we have generated transcriptomic data for body tissues and salivary and venom glands from five species of venomous and nonvenomous reptiles. Our comparative transcriptomic analysis of these data reveals that snake venom does not evolve through the hypothesized process of duplication and recruitment of genes encoding body proteins. Indeed, our results show that many proposed venom toxins are in fact expressed in a wide variety of body tissues, including the salivary gland of nonvenomous reptiles and that these genes have therefore been restricted to the venom gland following duplication, not recruited. Thus, snake venom evolves through the duplication and subfunctionalization of genes encoding existing salivary proteins. These results highlight the danger of the elegant and intuitive "just-so story" in evolutionary biology.

  9. Snake venoms: A brief treatise on etymology, origins of terminology, and definitions.

    PubMed

    Weinstein, Scott A

    2015-09-01

    The ancient perceptions of "venomous" and "poisonous snakes", as well as the Indo-European (IE) etymological origins of the term "venom" specifically associated with snakes are considered. Although several ancient cultures perceived snakes as symbols of fecundity and renewal, concurrent beliefs also associated venomous snakes with undesirable human characteristics or as portending non-propitious events. The respective IE roots of the terms "venom" and "poison", "wen" and "poi" refer to desire or the act of ingesting liquids. The origin of the term, "venom", is associated with polytheistic cults that emphasized attainment of desires sometimes assisted by "love potions", a term later interpolated with the word, "poison". Specific interpretation of the term, venom, has varied since its first probable use in the mid-Thirteenth Century. The definition of snake venom has long been contended, and interpretations have often reflected emphasis on the pharmacological or experimental toxicity of medically relevant snake venoms with less regard for the basic biological bases of these venoms, as well as those from snakes with no known medical significance. Several definitions of "snake venom" and their defining criteria are reviewed, and critical consideration is given to traditional criteria that might facilitate the future establishment of a biologically accurate definition.

  10. Differences in venom toxicity and antigenicity between females and males Tityus nororientalis (Buthidae) scorpions

    PubMed Central

    De Sousa, Leonardo; Borges, Adolfo; Vásquez-Suárez, Aleikar; Op den Camp, Huub JM; Chadee-Burgos, Rosa I; Romero-Bellorín, Mirna; Espinoza, Jorge; De Sousa-Insana, Leonardo; Pino-García, Oscar

    2010-01-01

    Venom from male and female specimens of the medically important Venezuelan scorpion Tityus nororientalis have been compared. Males showed a significantly higher venom yield (2.39mg/individual) compared to female scorpions (0.98mg/individual). Female venom was significantly more toxic than that of males, with a median lethal dose (LD50) in C57BL/6 mice of 9.46 μg venom protein/gm body weight [95% confidence interval (8.91-9.94)] whereas LD50 for males was 13.36(12.58-14.03) μg/gm. Mass spectral analyses by MALDI-TOF revealed differences in venom composition between males and females. From a clinical standpoint, the time course of toxicity course indicated a tendency, in the case of the female venom, to elicit the earlier occurrence of severe signs such as sialorrhea, dyspnea (bradypnea/apnea) and exophthalmus particularly in the late toxicity phase. Female venom was significantly less efficient than male venom to inhibit the binding of anti-T. discrepans antibodies to immobilized T. discrepans venom in ELISA assays, suggesting sex-related differences in the bioactive surfaces of T. nororientalis toxins. These results indicate that males and females of T. nororientalis produce venoms with different composition and activity which may have epidemiological implications. PMID:21544184

  11. The in vivo cardiovascular effects of an Australasian box jellyfish (Chiropsalmus sp.) venom in rats.

    PubMed

    Ramasamy, Sharmaine; Isbister, Geoffrey K; Seymour, Jamie E; Hodgson, Wayne C

    2005-03-01

    Using a new technique to extract venom from the nematocysts of jellyfish, the in vivo cardiovascular effects of Chiropsalmus sp. venom were investigated in anaesthetized rats. Chiropsalmus sp. venom (150 microg/kg, i.v.) produced a transient hypertensive response (44+/-4 mmHg; n=6) followed by hypotension and cardiovascular collapse. Concurrent artificial respiration or pretreatment with Chironex fleckeri antivenom (AV, 3000 U/kg, i.v.) did not have any effect on the venom-induced hypertensive response nor the subsequent cardiovascular collapse. The cardiovascular response of animals receiving venom after the infusion of MgSO4 (50-70 mM @ 0.25 ml/min, i.v.; n=5) alone, or in combination with AV (n=5), was not significantly different from rats receiving venom alone. Prior administration of prazosin (50 microg/kg, i.v.; n=4) or ketanserin (1 mg/kg, i.v.; n=4) did not significantly attenuate the hypertensive response nor prevent the cardiovascular collapse induced by venom (50 microg/kg, i.v.). In contrast to previous work examining C. fleckeri venom, administration of AV alone, or in combination with MgSO4, was not effective in preventing cardiovascular collapse following the administration of Chiropsalmus sp. venom. This indicates that the venom of the two related box jellyfish contain different lethal components and highlights the importance of species identification prior to initiating treatment regimes following jellyfish envenoming.

  12. Molecular Diversity and Gene Evolution of the Venom Arsenal of Terebridae Predatory Marine Snails

    PubMed Central

    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

    2015-01-01

    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. PMID:26025559

  13. Variation in venom yield and protein concentration of the centipedes Scolopendra polymorpha and Scolopendra subspinipes.

    PubMed

    Cooper, Allen M; Fox, Gerad A; Nelsen, David R; Hayes, William K

    2014-05-01

    Venom generally comprises a complex mixture of compounds representing a non-trivial metabolic expense. Accordingly, natural selection should fine-tune the amount of venom carried within an animal's venom gland(s). The venom supply of scolopendromorph centipedes likely influences their venom use and has implications for the severity of human envenomations, yet we understand very little about their venom yields and the factors influencing them. We investigated how size, specifically body length, influenced volume yield and protein concentration of electrically extracted venom in Scolopendra polymorpha and Scolopendra subspinipes. We also examined additional potential influences on yield in S. polymorpha, including relative forcipule size, relative mass, geographic origin (Arizona vs. California), sex, time in captivity, and milking history. Volume yield was linearly related to body length, and S. subspinipes yielded a larger length-specific volume than S. polymorpha. Body length and protein concentration were uncorrelated. When considering multiple influences on volume yield in S. polymorpha, the most important factor was body length, but yield was also positively associated with relative forcipule length and relative body mass. S. polymorpha from California yielded a greater volume of venom with a higher protein concentration than conspecifics from Arizona, all else being equal. Previously milked animals yielded less venom with a lower protein concentration. For both species, approximately two-thirds of extractable venom was expressed in the first two pulses, with remaining pulses yielding declining amounts, but venom protein concentration did not vary across pulses. Further study is necessary to ascertain the ecological significance of the factors influencing venom yield and how availability may influence venom use.

  14. An examination of cardiovascular collapse induced by eastern brown snake (Pseudonaja textilis) venom.

    PubMed

    Chaisakul, Janeyuth; Isbister, Geoffrey K; Kuruppu, Sanjaya; Konstantakopoulos, Nicki; Hodgson, Wayne C

    2013-08-29

    The Pseudonaja genus (Brown snakes) is widely distributed across Australia and bites account for significant mortality. Venom-induced consumption coagulopathy (VICC) and, less often, early cardiovascular collapse occur following envenoming by these snakes. We have previously examined possible mechanism(s) behind the early cardiovascular collapse following Papuan taipan (Oxyuranus scutellatus) envenoming. In the present study, we investigate early cardiovascular collapse in anaesthetized rats following administration of eastern brown snake (Pseudonaja textilis) venom, and prevention of this effect with prior administration of 'priming' doses (i.e. doses of venom which caused a transient hypotensive response) of venom. P. textilis venom (5-10 μg/kg, i.v.) induced cardiovascular collapse in anaesthetized rats, characterized by a rapid decrease in systolic blood pressure until non recordable. Prior administration of 'priming' doses of P. textilis venom (2 and 3 μg/kg) or, at least, 4-5 doses of O. scutellatus (2 μg/kg, i.v.) or Daboia russelii limitis (20 μg/kg, i.v.) venoms prevented cardiovascular collapse induced by P. textilis venom. Moreover, early collapse was also inhibited by prior administration of 2 discrete doses of Acanthophis rugosus venom. Prior administration of commercial polyvalent snake antivenom (500-3000 units/kg, i.v.) or heparin (300 units/kg, i.v.) also inhibited P. textilis venom-induced cardiovascular collapse. Our results indicate that P. textilis venom-induced cardiovascular collapse can be prevented by prior administration of sub-lethal doses of venom from P. textilis, O. scutellatus, A. rugosus and D. russelii limitis. This suggests that sudden cardiovascular collapse following envenoming is likely to involve a common mechanism/pathway activated by different snake venoms.

  15. Venomous snakebites in children in southern Croatia.

    PubMed

    Karabuva, Svjetlana; Vrkić, Ivana; Brizić, Ivica; Ivić, Ivo; Lukšić, Boris

    2016-03-15

    This retrospective study represents observation of 160 children and adolescents aged up to 18 years that experienced venomous snakebites in southern Croatia and were treated in the Clinical Department of Infectious Diseases in the University Hospital Centre Split from 1979 to 2013. The main purpose of this research was to determine the epidemiological characteristics, clinical presentation, local and general complications, and received treatment. Most bites occurred during warm months, from early May to late August (80%), mostly in May and June. Upper limb bites were more frequent (59%) than lower limb bites (40%). Out of the total number of poisoned children, 24% developed local, and 25% general complications. The most common local complications were haemorrhagic blisters that occurred in 20% children, followed by compartment syndrome presented in 7.5% patients. The most dominated general complication was cranial nerve paresis or paralysis, which was identified in 11.2% patients, whereas shock symptoms were registrated in 7% children. According to severity of poisoning, 9.4% children had minor, 35% mild, 30.6% moderate, and 24.4% had severe clinical manifestation of envenomation. Only one (0.6%) child passed away because of snakebite directly on the neck. All patients received antivenom produced by the Institute of Immunology in Zagreb, tetanus prophylaxis as well, and almost all of them received antibiotics, and a great majority of them also received corticosteroids and antihistamines. Neighter anaphylactic reaction nor serum disease were noticed in our patients after administrating antivenom. A total of 26% children underwent surgical interventions, and incision of haemorrhagic blister was the most common applied surgical treatment, which was preformed in 15.6% patients, while fasciotomy was done in 7.5% subjects. All of our surgically treated patients recovered successfully.

  16. Cobra venom cytotoxins; apoptotic or necrotic agents?

    PubMed

    Ebrahim, Karim; Shirazi, Farshad H; Mirakabadi, Abbas Zare; Vatanpour, Hossein

    2015-12-15

    Organs homeostasis is controlled by a dynamic balance between cell proliferation and apoptosis. Failure to induction of apoptosis has been implicated in tumor development. Cytotoxin-I (CTX-I) and cytotoxin-II (CTX-II) are two physiologically active polypeptides found in Caspian cobra venom. Anticancer activity and mechanism of cell death induced by these toxins have been studied. The toxins were purified by different chromatographic steps and their cytotoxicity and pattern of cell death were determined by MTT, LDH release, acridine orange/ethidium bromide (AO/EtBr) double staining, flow cytometric analysis, caspase-3 activity and neutral red assays. The IC50 of CTX-II in MCF-7, HepG2, DU-145 and HL-60 was 4.1 ± 1.3, 21.2 ± 4.4, 9.4 ± 1.8 μg/mL and 16.3 ± 1.9 respectively while the IC50 of this toxin in normal MDCK cell line was 54.5 ± 3.9 μg/mL. LDH release suddenly increase after a specific toxins concentrations in all cell lines. AO/EtBr double staining, flow cytometric analysis and caspase-3 activity assay confirm dose and time-dependent induction of apoptosis by both toxins. CTX-I and CTX-II treated cells lost their lysosomal membrane integrity and couldn't uptake neutral red day. CTX-I and CTX-II showed significant anticancer activity with minimum effects on normal cells and better IC50 compared to current anticancer drug; cisplatin. They induce their apoptotic effect via lysosomal pathways and release of cathepsins to cytosol. These effects were seen in limited rage of toxins concentrations and pattern of cell death rapidly changes to necrosis by increase in toxin's concentration. In conclusion, significant apoptogenic effects of these toxins candidate them as a possible anticancer agent.

  17. 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...

  18. Natural Inhibitors of Snake Venom Metalloendopeptidases: History and Current Challenges

    PubMed Central

    Bastos, Viviane A.; Gomes-Neto, Francisco; Perales, Jonas; Neves-Ferreira, Ana Gisele C.; Valente, Richard H.

    2016-01-01

    The research on natural snake venom metalloendopeptidase inhibitors (SVMPIs) began in the 18th century with the pioneering work of Fontana on the resistance that vipers exhibited to their own venom. During the past 40 years, SVMPIs have been isolated mainly from the sera of resistant animals, and characterized to different extents. They are acidic oligomeric glycoproteins that remain biologically active over a wide range of pH and temperature values. Based on primary structure determination, mammalian plasmatic SVMPIs are classified as members of the immunoglobulin (Ig) supergene protein family, while the one isolated from muscle belongs to the ficolin/opsonin P35 family. On the other hand, SVMPIs from snake plasma have been placed in the cystatin superfamily. These natural antitoxins constitute the first line of defense against snake venoms, inhibiting the catalytic activities of snake venom metalloendopeptidases through the establishment of high-affinity, non-covalent interactions. This review presents a historical account of the field of natural resistance, summarizing its main discoveries and current challenges, which are mostly related to the limitations that preclude three-dimensional structural determinations of these inhibitors using “gold-standard” methods; perspectives on how to circumvent such limitations are presented. Potential applications of these SVMPIs in medicine are also highlighted. PMID:27571103

  19. Natural Inhibitors of Snake Venom Metalloendopeptidases: History and Current Challenges.

    PubMed

    Bastos, Viviane A; Gomes-Neto, Francisco; Perales, Jonas; Neves-Ferreira, Ana Gisele C; Valente, Richard H

    2016-08-26

    The research on natural snake venom metalloendopeptidase inhibitors (SVMPIs) began in the 18th century with the pioneering work of Fontana on the resistance that vipers exhibited to their own venom. During the past 40 years, SVMPIs have been isolated mainly from the sera of resistant animals, and characterized to different extents. They are acidic oligomeric glycoproteins that remain biologically active over a wide range of pH and temperature values. Based on primary structure determination, mammalian plasmatic SVMPIs are classified as members of the immunoglobulin (Ig) supergene protein family, while the one isolated from muscle belongs to the ficolin/opsonin P35 family. On the other hand, SVMPIs from snake plasma have been placed in the cystatin superfamily. These natural antitoxins constitute the first line of defense against snake venoms, inhibiting the catalytic activities of snake venom metalloendopeptidases through the establishment of high-affinity, non-covalent interactions. This review presents a historical account of the field of natural resistance, summarizing its main discoveries and current challenges, which are mostly related to the limitations that preclude three-dimensional structural determinations of these inhibitors using "gold-standard" methods; perspectives on how to circumvent such limitations are presented. Potential applications of these SVMPIs in medicine are also highlighted.

  20. Wasp Venom Toxins as a Potential Therapeutic Agent.

    PubMed

    Dongol, Yashad; Dhananjaya, Bhadrapara L; Shrestha, Rakesh K; Aryal, Gopi

    2016-01-01

    It is high time now to discover novel drugs due to the increasing rate of drug resistance by the pathogen organisms and target cells as well as the dependence or tolerance of the body towards the drug. As it is obvious that significant numbers of the modern day pharmaceuticals are derived from natural products, it is equally astonishing to accept that venoms of various origins have therapeutic potentials. Wasp venoms are also a rich source of therapeutically important toxins which includes short cationic peptides, kinins, polyamines and polyDNA viruses, to name a few indentified. Wasp venom cationic peptides, namely mastoparan and its analogs, show a very important potency as an antimicrobial and anticancer agents of the future. They have proven to be the better candidates due to their lesser toxic effects and higher selectivity upon chemical modification and charge optimization. They also have superiority over the conventional chemical drugs as the target cells very rarely develop resistance against them because these peptides primarily imparts its effect through biophysical interaction with the target cell membrane which is dependent upon the net charge of the peptide, its hydrophobicity and anionicity and fluidity of the target cell membranes. Besides, the other components of wasp venom such as kinins, polyamines and polyDNA viruses show various pharmacological promise in the treatment of pain, inflammatory disease, and neurodegenerative diseases such as epilepsy and aversion.

  1. Peptidome profiling of venom from the social wasp Polybia paulista.

    PubMed

    Dias, Nathalia Batista; de Souza, Bibiana Monson; Gomes, Paulo Cesar; Brigatte, Patricia; Palma, Mario Sergio

    2015-12-01

    Most crude venom from Polybia paulista is composed of short, linear peptides; however, only five of these peptides are structurally and functionally characterized. Therefore, the peptides in this venom were profiled using an HPLC-IT-TOF/MS and MS(n) system. The presence of type -d and -w ions that are generated from the fragmentation of the side chains was used to resolve I/L ambiguity. The distinction between K and Q residues was achieved through esterification of the α- and ε-amino groups in the peptide chains, followed by mass spectrometry analysis. Fourteen major peptides were detected in P. paulista venom and sequenced; all the peptides were synthesized on solid-phase and submitted to a series of bioassays. Five of them had been previously characterized, and nine were novel toxins. The novel peptides correspond to two wasp kinins, two chemotactic components, three mastoparans, and two peptides of unknown function. The seven novel peptides with identified functions appear to act synergistically with the previously known ones, constituting three well-known families of peptide toxins (wasp kinins, chemotactic peptides, and mastoparans) in the venom of social wasps. These multifunctional toxins can cause pain, oedema formation, haemolysis, chemotaxis of PMNLs, and mast cell degranulation in victims who are stung by wasps.

  2. Deaths From Bites and Stings of Venomous Animals

    PubMed Central

    Ennik, Franklin

    1980-01-01

    Data abstracted from 34 death certificates indicate that the three venomous animal groups most often responsible for human deaths in California from 1960 through 1976 were Hymenoptera (bees, wasps, ants and the like) (56 percent), snakes (35 percent) and spiders (6 percent). An average incidence of 2.0 deaths per year occurred during these 17 years, or an average death rate of 0.01 per 100,000 population per year. Nearly three times more males than females died of venomous animal bites and stings. Half of the deaths from venomous snake bites occurred in children younger than 5 years of age. Susceptible persons 40 years or older appeared to be particularly vulnerable to hymenopterous insect stings and often quickly died of anaphylaxis. Fatal encounters with venomous animals occurred more often around the home than at places of employment or during recreational activities. Deaths resulting from spider bites are rare in California but many bites are reported. Medical practitioners are urged to seek professional assistance in identifying offending animals causing human discomfort and to use these animals' scientific names on death certificates and in journal articles. ImagesIGN. PMID:7467305

  3. 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...

  4. 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...

  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...

  6. Hemolytic venoms from marine cnidarian jellyfish – an overview

    PubMed Central

    Mariottini, Gian Luigi

    2014-01-01

    Cnidarian jellyfish are viewed as an emergent problem in several coastal zones throughout the world. Recurrent outbreaks pose a serious threat to tourists and bathers, as well as to sea-workers, involving health and economical aspects. As a rule, cnidarian stinging as a consequence of nematocyst firing induces merely local symptoms but cardiovascular or neurological complications can also occur. Hemolysis is a frequent effect of cnidarian stinging; this dangerous condition is known to be caused by several venoms and can sometimes be lethal. At present, the bulk of data concerning hemolytic cnidarian venoms comes from the study of benthic species, such as sea anemones and soft corals, but hemolytic factors were found in venoms of several siphonophore, cubozoan and scyphozoan jellyfish, which are mainly involved in the envenomation of bathers and sea-workers. Therefore, the aim of this paper is to review the scientific literature concerning the hemolytic venoms from cnidarian jellyfish taking into consideration their importance in human pathology as well as health implications and possible therapeutic measures. PMID:25386336

  7. 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

  8. Venom Gland Transcriptomic and Proteomic Analyses of the Enigmatic Scorpion Superstitionia donensis (Scorpiones: Superstitioniidae), with Insights on the Evolution of Its Venom Components.

    PubMed

    Santibáñez-López, Carlos E; Cid-Uribe, Jimena I; Batista, Cesar V F; Ortiz, Ernesto; Possani, Lourival D

    2016-12-09

    Venom gland transcriptomic and proteomic analyses have improved our knowledge on the diversity of the heterogeneous components present in scorpion venoms. However, most of these studies have focused on species from the family Buthidae. To gain insights into the molecular diversity of the venom components of scorpions belonging to the family Superstitioniidae, one of the neglected scorpion families, we performed a transcriptomic and proteomic analyses for the species Superstitionia donensis. The total mRNA extracted from the venom glands of two specimens was subjected to massive sequencing by the Illumina protocol, and a total of 219,073 transcripts were generated. We annotated 135 transcripts putatively coding for peptides with identity to known venom components available from different protein databases. Fresh venom collected by electrostimulation was analyzed by LC-MS/MS allowing the identification of 26 distinct components with sequences matching counterparts from the transcriptomic analysis. In addition, the phylogenetic affinities of the found putative calcins, scorpines, La1-like peptides and potassium channel κ toxins were analyzed. The first three components are often reported as ubiquitous in the venom of different families of scorpions. Our results suggest that, at least calcins and scorpines, could be used as molecular markers in phylogenetic studies of scorpion venoms.

  9. Venom Gland Transcriptomic and Proteomic Analyses of the Enigmatic Scorpion Superstitionia donensis (Scorpiones: Superstitioniidae), with Insights on the Evolution of Its Venom Components

    PubMed Central

    Santibáñez-López, Carlos E.; Cid-Uribe, Jimena I.; Batista, Cesar V. F.; Ortiz, Ernesto; Possani, Lourival D.

    2016-01-01

    Venom gland transcriptomic and proteomic analyses have improved our knowledge on the diversity of the heterogeneous components present in scorpion venoms. However, most of these studies have focused on species from the family Buthidae. To gain insights into the molecular diversity of the venom components of scorpions belonging to the family Superstitioniidae, one of the neglected scorpion families, we performed a transcriptomic and proteomic analyses for the species Superstitionia donensis. The total mRNA extracted from the venom glands of two specimens was subjected to massive sequencing by the Illumina protocol, and a total of 219,073 transcripts were generated. We annotated 135 transcripts putatively coding for peptides with identity to known venom components available from different protein databases. Fresh venom collected by electrostimulation was analyzed by LC-MS/MS allowing the identification of 26 distinct components with sequences matching counterparts from the transcriptomic analysis. In addition, the phylogenetic affinities of the found putative calcins, scorpines, La1-like peptides and potassium channel κ toxins were analyzed. The first three components are often reported as ubiquitous in the venom of different families of scorpions. Our results suggest that, at least calcins and scorpines, could be used as molecular markers in phylogenetic studies of scorpion venoms. PMID:27941686

  10. Laterally Transferred Gene Recruited as a Venom in Parasitoid Wasps.

    PubMed

    Martinson, Ellen O; Martinson, Vincent G; Edwards, Rachel; Mrinalini; Werren, John H

    2016-04-01

    Parasitoid wasps use venom to manipulate the immunity and metabolism of their host insects in a variety of ways to provide resources for their offspring. Yet, how genes are recruited and evolve to perform venom functions remain open questions. A recently recognized source of eukaryotic genome innovation is lateral gene transfer (LGT). Glycoside hydrolase family 19 (GH19) chitinases are widespread in bacteria, microsporidia, and plants where they are used in nutrient acquisition or defense, but have previously not been known in metazoans. In this study, a GH19 chitinase LGT is described from the unicellular microsporidia/Rozella clade into parasitoid wasps of the superfamily Chalcidoidea, where it has become recruited as a venom protein. The GH19 chitinase is present in 15 species of chalcidoid wasps representing four families, and phylogenetic analysis indicates that it was laterally transferred near or before the origin of Chalcidoidea (∼95 Ma). The GH19 chitinase gene is highly expressed in the venom gland of at least seven species, indicating a role in the complex host manipulations performed by parasitoid wasp venom. RNAi knockdown in the model parasitoid Nasonia vitripennis reveals that-following envenomation-the GH19 chitinase induces fly hosts to upregulate genes involved in an immune response to fungi. A second, independent LGT of GH19 chitinase from microsporidia into mosquitoes was also found, also supported by phylogenetic reconstructions. Besides these two LGT events, GH19 chitinase is not found in any other sequenced animal genome, or in any fungi outside the microsporidia/Rozella clade.

  11. Development of a sensitive enzyme immunoassay for measuring taipan venom in serum.

    PubMed

    Kulawickrama, S; O'Leary, M A; Hodgson, W C; Brown, S G A; Jacoby, T; Davern, K; Isbister, G K

    2010-07-01

    The detection and measurement of snake venom in blood is important for confirming snake identification, determining when sufficient antivenom has been given, detecting recurrence of envenoming, and in forensic investigation. Venom enzyme immunoassays (EIA) have had persistent problems with poor sensitivity and high background absorbance leading to false positive results. This is particularly problematic with Australasian snakes where small amounts of highly potent venom are injected, resulting in low concentrations being associated with severe clinical effects. We aimed to develop a venom EIA with a limit of detection (LoD) sufficient to accurately distinguish mild envenoming from background absorbance at picogram concentrations of venom in blood. Serum samples were obtained from patients with taipan bites (Oxyuranus spp.) before and after antivenom, and from rats given known venom doses. A sandwich EIA was developed using biotinylated rabbit anti-snake venom antibodies for detection. For low venom concentrations (i.e. <1 ng/mL) the assay was done before and after addition of antivenom to the sample (antivenom difference method). The LoD was 0.15 ng/mL for the standard assay and 0.1 ng/mL for the antivenom difference method. In 11 pre-antivenom samples the median venom concentration was 10 ng/mL (Range: 0.3-3212 ng/mL). In four patients with incomplete venom-induced consumption coagulopathy the median venom concentration was 2.4 ng/mL compared to 30 ng/mL in seven patients with complete venom-induced consumption coagulopathy. No venom was detected in any post-antivenom sample and the median antivenom dose prior to this first post-antivenom sample was 1.5 vials (1-3 vials), including 7 patients administered only 1 vial. In rats the assay distinguished a 3-fold difference in venom dose administered and there was small inter-individual variability. There was small but measurable cross-reactivity with black snake (Pseudechis), tiger snake (Notechis) and rough

  12. Snake venomics of the lancehead pitviper Bothrops asper: geographic, individual, and ontogenetic variations.

    PubMed

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

    2008-08-01

    We report the comparative proteomic characterization of the venoms of adult and newborn specimens of the lancehead pitviper Bothrops asper from two geographically isolated populations from the Caribbean and the Pacific versants of Costa Rica. The crude venoms were fractionated by reverse-phase HPLC, followed by analysis of each chromatographic fraction by SDS-PAGE, N-terminal sequencing, MALDI-TOF mass fingerprinting, and collision-induced dissociation tandem mass spectrometry of tryptic peptides. The two B. asper populations, separated since the late Miocene or early Pliocene (8-5 mya) by the Guanacaste Mountain Range, Central Mountain Range, and Talamanca Mountain Range, contain both identical and different (iso)enzymes from the PLA 2, serine proteinase, and SVMP families. Using a similarity coefficient, we estimate that the similarity of venom proteins between the two B. asper populations may be around 52%. Compositional differences between venoms among different geographic regions may be due to evolutionary environmental pressure acting on isolated populations. To investigate venom variability among specimens from the two B. asper populations, the reverse-phase HPLC protein profiles of 15 venoms from Caribbean specimens and 11 venoms from snakes from Pacific regions were compared. Within each B. asper geographic populations, all major venom protein families appeared to be subjected to individual variations. The occurrence of intraspecific individual allopatric variability highlights the concept that a species, B. asper in our case, should be considered as a group of metapopulations. Analysis of pooled venoms of neonate specimens from Caribbean and Pacific regions with those of adult snakes from the same geographical habitat revealed prominent ontogenetic changes in both geographical populations. Major ontogenetic changes appear to be a shift from a PIII-SVMP-rich to a PI-SVMP-rich venom and the secretion in adults of a distinct set of PLA 2 molecules than in

  13. Combined venomics, venom gland transcriptomics, bioactivities, and antivenomics of two Bothrops jararaca populations from geographic isolated regions within the Brazilian Atlantic rainforest.

    PubMed

    Gonçalves-Machado, Larissa; Pla, Davinia; Sanz, Libia; Jorge, Roberta Jeane B; Leitão-De-Araújo, Moema; Alves, Maria Lúcia M; Alvares, Diego Janisch; De Miranda, Joari; Nowatzki, Jenifer; de Morais-Zani, Karen; Fernandes, Wilson; Tanaka-Azevedo, Anita Mitico; Fernández, Julián; Zingali, Russolina B; Gutiérrez, José María; Corrêa-Netto, Carlos; Calvete, Juan J

    2016-03-01

    Bothrops jararaca is a slender and semi-arboreal medically relevant pit viper species endemic to tropical and subtropical forests in southern Brazil, Paraguay, and northern Argentina (Misiones). Within its geographic range, it is often abundant and is an important cause of snakebite. Although no subspecies are currently recognized, geographic analyses have revealed the existence of two well-supported B. jararaca clades that diverged during the Pliocene ~3.8Mya and currently display a southeastern (SE) and a southern (S) Atlantic rainforest (Mata Atlântica) distribution. The spectrum, geographic variability, and ontogenetic changes of the venom proteomes of snakes from these two B. jararaca phylogroups were investigated applying a combined venom gland transcriptomic and venomic analysis. Comparisons of the venom proteomes and transcriptomes of B. jararaca from the SE and S geographic regions revealed notable interpopulational variability that may be due to the different levels of population-specific transcriptional regulation, including, in the case of the southern population, a marked ontogenetic venom compositional change involving the upregulation of the myotoxic PLA2 homolog, bothropstoxin-I. This population-specific marker can be used to estimate the proportion of venom from the southern population present in the B. jararaca venom pool used for the Brazilian soro antibotrópico (SAB) antivenom production. On the other hand, the southeastern population-specific D49-PLA2 molecules, BinTX-I and BinTX-II, lend support to the notion that the mainland ancestor of Bothrops insularis was originated within the same population that gave rise to the current SE B. jararaca phylogroup, and that this insular species endemic to Queimada Grande Island (Brazil) expresses a pedomorphic venom phenotype. Mirroring their compositional divergence, the two geographic B. jararaca venom pools showed distinct bioactivity profiles. However, the SAB antivenom manufactured in Vital Brazil

  14. Venomics of Naja sputatrix, the Javan spitting cobra: A short neurotoxin-driven venom needing improved antivenom neutralization.

    PubMed

    Tan, Nget Hong; Wong, Kin Ying; Tan, Choo Hock

    2017-03-22

    The venom proteome of Naja sputatrix (Javan spitting cobra) was elucidated through reverse-phase HPLC, nano-ESI-LCMS/MS and data mining. A total of 97 distinct protein forms belonging to 14 families were identified. The most abundant proteins are the three-finger toxins (3FTXs, 64.22%) and phospholipase A2 (PLA2, 31.24%), followed by nerve growth factors (1.82%), snake venom metalloproteinase (1.33%) and several proteins of lower abundance (<1%) including a variety of venom enzymes. At subproteome, the 3FTx is dominated by cytotoxins (48.08%), while short neurotoxins (7.89%) predominate over the long neurotoxins (0.48%) among other neurotoxins of lesser toxicity (muscarinic toxin-like proteins, 5.51% and weak neurotoxins, 2.26%). The major SNTX, CTX and PLA2 toxins were isolated with intravenous median lethal doses determined as 0.13, 1.06 and 0.50μg/g in mice, respectively. SABU, the Indonesia manufactured homologous tri-specific antivenom could neutralize the CTX and PLA2 fraction with moderate potency (potency=0.14-0.16mg toxin per ml antivenom). The SNTX, however, was very poorly neutralized with a potency level of 0.034mg/ml, indicating SNTX as the main limiting factor in antivenom neutralization. The finding helps elucidate the inferior efficacy of SABU reported in neutralizing N. sputatrix venom, and supports the call for antivenom improvement.

  15. Spider genomes provide insight into composition and evolution of venom and silk

    PubMed Central

    Sanggaard, Kristian W.; Bechsgaard, Jesper S.; Fang, Xiaodong; Duan, Jinjie; Dyrlund, Thomas F.; Gupta, Vikas; Jiang, Xuanting; Cheng, Ling; Fan, Dingding; Feng, Yue; Han, Lijuan; Huang, Zhiyong; Wu, Zongze; Liao, Li; Settepani, Virginia; Thøgersen, Ida B.; Vanthournout, Bram; Wang, Tobias; Zhu, Yabing; Funch, Peter; Enghild, Jan J.; Schauser, Leif; Andersen, Stig U.; Villesen, Palle; Schierup, Mikkel H; Bilde, Trine; Wang, Jun

    2014-01-01

    Spiders are ecologically important predators with complex venom and extraordinarily tough silk that enables capture of large prey. Here we present the assembled genome of the social velvet spider and a draft assembly of the tarantula genome that represent two major taxonomic groups of spiders. The spider genomes are large with short exons and long introns, reminiscent of mammalian genomes. Phylogenetic analyses place spiders and ticks as sister groups supporting polyphyly of the Acari. Complex sets of venom and silk genes/proteins are identified. We find that venom genes evolved by sequential duplication, and that the toxic effect of venom is most likely activated by proteases present in the venom. The set of silk genes reveals a highly dynamic gene evolution, new types of silk genes and proteins, and a novel use of aciniform silk. These insights create new opportunities for pharmacological applications of venom and biomaterial applications of silk. PMID:24801114

  16. Proteomic Analyses of Agkistrodon contortrix contortrix Venom Using 2D Electrophoresis and MS Techniques.

    PubMed

    Bocian, Aleksandra; Urbanik, Małgorzata; Hus, Konrad; Łyskowski, Andrzej; Petrilla, Vladimír; Andrejčáková, Zuzana; Petrillová, Monika; Legáth, Jaroslav

    2016-12-13

    Snake venom is a complex mixture of proteins and peptides which in the Viperidae is mainly hemotoxic. The diversity of these components causes the venom to be an extremely interesting object of study. Discovered components can be used in search for new pharmaceuticals used primarily in the treatment of diseases of the cardiovascular system. In order to determine the protein composition of the southern copperhead venom, we have used high resolution two dimensional electrophoresis and MALDI ToF/ToF MS-based identification. We have identified 10 groups of proteins present in the venom, of which phospholipase A₂ and metalloprotease and serine proteases constitute the largest groups. For the first time presence of 5'-nucleotidase in venom was found in this group of snakes. Three peptides present in the venom were also identified. Two of them as bradykinin-potentiating agents and one as an inhibitor.

  17. Proteomic Analyses of Agkistrodon contortrix contortrix Venom Using 2D Electrophoresis and MS Techniques

    PubMed Central

    Bocian, Aleksandra; Urbanik, Małgorzata; Hus, Konrad; Łyskowski, Andrzej; Petrilla, Vladimír; Andrejčáková, Zuzana; Petrillová, Monika; Legáth, Jaroslav

    2016-01-01

    Snake venom is a complex mixture of proteins and peptides which in the Viperidae is mainly hemotoxic. The diversity of these components causes the venom to be an extremely interesting object of study. Discovered components can be used in search for new pharmaceuticals used primarily in the treatment of diseases of the cardiovascular system. In order to determine the protein composition of the southern copperhead venom, we have used high resolution two dimensional electrophoresis and MALDI ToF/ToF MS-based identification. We have identified 10 groups of proteins present in the venom, of which phospholipase A2 and metalloprotease and serine proteases constitute the largest groups. For the first time presence of 5′-nucleotidase in venom was found in this group of snakes. Three peptides present in the venom were also identified. Two of them as bradykinin-potentiating agents and one as an inhibitor. PMID:27983581

  18. Cobra venom contains a pool of cysteine-rich secretory proteins.

    PubMed

    Osipov, Alexey V; Levashov, Mikhail Yu; Tsetlin, Victor I; Utkin, Yuri N

    2005-03-04

    A large family of cysteine-rich secretory proteins (CRISPs) includes proteins of different origin, the function of the majority of CRISPs being unknown. For CRISPs isolated from snake venom, two types of activities were found: two proteins blocked cyclic nucleotide-gated ion channels, several others blocked potassium-stimulated smooth muscle contraction. Thus, snake CRISPs represent potentially valuable tools for studies of ion channels, which makes promising a search for new CRISPs. Here we report on the isolation of several novel CRISPs from the venoms of Asian cobra Naja kaouthia and African cobra Naja haje using a combination of different types of liquid chromatography. Four CRISP variants were identified in N. kaouthia venom and three proteins, one of them acidic, were found in N. haje venom. Acidic CRISP was found in a reptilian venom for the first time. Our data suggest that each cobra venom contains a pool of different CRISPs.

  19. Partial in vitro analysis of toxic and antigenic activities of eleven Peruvian pitviper snake venoms.

    PubMed

    Guerra-Duarte, C; Lopes-Peixoto, J; Fonseca-de-Souza, B R; Stransky, S; Oliveira, D; Schneider, F S; Lopes-de-Souza, L; Bonilla, C; Silva, W; Tintaya, B; Yarleque, A; Chávez-Olórtegui, C

    2015-12-15

    This work used eleven Peruvian snake venoms (Bothrops andianus, Bothrops atrox, Bothrops barnetti, Bothrops castelnaudi, Bothriopsis chloromelas, Bothrocophias microphthalmus, Bothrops neuwiedi, Bothriopsis oligolepis, Bothriopsis peruviana, Bothrops pictus and Bothriopsis taeniata) to perform in vitro experimentation and determine its main characteristics. Hyaluronidase (HYAL), phospholipase A2 (PLA2), snake venom metalloproteinase (SVMP), snake venom serine protease (SVSP) and L-amino acid oxidase (LAAO) activities; toxicity by cell viability assays using MGSO3, VERO and HeLa cell lineages; and crossed immunoreactivity with Peruvian (PAV) and Brazilian (BAV) antibothropic polyvalent antivenoms, through ELISA and Western Blotting assays, were determined. Results show that the activities tested in this study were not similar amongst the venoms and each species present their own peculiarities, highlighting the diversity within Bothrops complex. All venoms were capable of reducing cell viability of all tested lineages. It was also demonstrated the crossed recognition of all tested venoms by both antivenoms.

  20. ISOB: A Database of Indigenous Snake Species of Bangladesh with respective known venom composition

    PubMed Central

    Roly, Zahida Yesmin; Hakim, Md Abdul; Zahan, ASM Shahriar; Hossain, M Monzur; Reza, Md Abu

    2015-01-01

    At present there is no well structured database available for the venomous snakes and venom composition of snakes in the world although venom has immense importance in biomedical research. Searching for a specific venom component from NCBI, PDB or public databases is troublesome, because they contain huge amount of data entries. Therefore, we created a database named “ISOB” which is a web accessible unique secondary database that represents the first online available bioinformatics resource showing venom composition of snakes. This database provides a comprehensive overview of seventy-eight indigenous snake species covering description of snakes supplemented with structural information of the relevant individual available venom proteins. We strongly believe that this database will contribute significantly in the field of bioinformatics, environmental research, proteomics, drug development and rationale drug designing. Availability The database is freely available at http://www.snakebd.com/ PMID:25848172

  1. A limited role for gene duplications in the evolution of platypus venom.

    PubMed

    Wong, Emily S W; Papenfuss, Anthony T; Whittington, Camilla M; Warren, Wesley C; Belov, Katherine

    2012-01-01

    Gene duplication followed by adaptive selection is believed to be the primary driver of venom evolution. However, to date, no studies have evaluated the importance of gene duplications for venom evolution using a genomic approach. The availability of a sequenced genome and a venom gland transcriptome for the enigmatic platypus provides a unique opportunity to explore the role that gene duplication plays in venom evolution. Here, we identify gene duplication events and correlate them with expressed transcripts in an in-season venom gland. Gene duplicates (1,508) were identified. These duplicated pairs (421), including genes that have undergone multiple rounds of gene duplications, were expressed in the venom gland. The majority of these genes are involved in metabolism and protein synthesis not toxin functions. Twelve secretory genes including serine proteases, metalloproteinases, and protease inhibitors likely to produce symptoms of envenomation such as vasodilation and pain were detected. Only 16 of 107 platypus genes with high similarity to known toxins evolved through gene duplication. Platypus venom C-type natriuretic peptides and nerve growth factor do not possess lineage-specific gene duplicates. Extensive duplications, believed to increase the potency of toxic content and promote toxin diversification, were not found. This is the first study to take a genome-wide approach in order to examine the impact of gene duplication on venom evolution. Our findings support the idea that adaptive selection acts on gene duplicates to drive the independent evolution and functional diversification of similar venom genes in venomous species. However, gene duplications alone do not explain the "venome" of the platypus. Other mechanisms, such as alternative splicing and mutation, may be important in venom innovation.

  2. Melt with this kiss: Paralysing and liquefying venom of the assassin bug Pristhesancus plagipennis (Hemiptera: Reduviidae).

    PubMed

    Walker, Andrew A; Madio, Bruno; Jin, Jiayi; Undheim, Eivind A B; Fry, Bryan G; King, Glenn F

    2017-01-27

    Assassin bugs (Hemiptera: Heteroptera: Reduviidae) are venomous insects, most of which prey on invertebrates. Assassin bug venom has features in common with venoms from other animals, such as paralysing and lethal activity when injected, and a molecular composition that includes disulfide-rich peptide neurotoxins. Uniquely, this venom also has strong liquefying activity that has been hypothesised to facilitate feeding through the narrow channel of the proboscis - a structure inherited from sap- and phloem-feeding phytophagous hemipterans and adapted during the evolution of Heteroptera into a fang and feeding structure. However, further understanding of the function of assassin bug venom is impeded by the lack of proteomic studies detailing its molecular composition. By using a combined transcriptomic/proteomic approach we show that the venom proteome of the harpactorine assassin bug Pristhesancus plagipennis includes a complex suite of >100 proteins comprising disulfide-rich peptides, CUB-domain proteins, cystatins, putative cytolytic toxins, triabin-like protein, odorant binding protein, serine proteases, catabolic enzymes, putative nutrient-binding proteins, plus eight families of proteins without homology to characterised proteins. Serine proteases, CUB domain proteins, putative cytolytic toxins, and other novel proteins in the 10-16 kDa mass range, were the most abundant venom components. Thus, in addition to putative neurotoxins, assassin bug venom includes a high proportion of enzymatic and cytolytic venom components likely to be well suited to tissue liquefaction. Our results also provide insight into the trophic switch to blood-feeding by the kissing bugs (Reduviidae: Triatominae). While some protein families such as triabins occur in the venoms of both predaceous and blood-feeding reduviids, the composition of venoms produced by these two groups is revealed to differ markedly. These results provide insights into the venom evolution in the insect suborder

  3. Thrombelastographic characterization of the thrombin-like activity of Crotalus simus and Bothrops asper venoms.

    PubMed

    Nielsen, Vance G; Boyer, Leslie V; Redford, Daniel T; Ford, Paul

    2016-06-16

    Annually, thousands suffer venomous snake-bite from Crotalus simus and Bothrops asper vipers in central and South America. The goals of the present study were to generally characterize the thrombin-like effects of venom from these snakes in human plasma with viscoelastic methods. Human plasma was exposed to the venom of three different C. simus subspecies and venoms obtained from B. asper vipers located in three different locations in Mexico. To characterize the factor X-activating and thrombin-like activity of these venoms, plasma (normal or factor XIII deficient) was pretreated with a variety of additives (e.g., heparin) in the absence or presence of calcium prior to exposure to 2.0 μg/ml of each viper's venom. These profiles were compared with plasma without venom that had contact activation of coagulation. Coagulation kinetics were determined with thrombelastography. All venoms had thrombin-like activity, with C. s. simus creating a slow growing, weak clot that was likely mediated by metalloproteinases. In contrast, B. asper venoms had rapid onset of coagulation and a high velocity of thrombus growth. Further, B. asper venom activity was calcium-independent, activated prothrombin, activated factor XIII, and independently polymerized fibrinogen. The viscoelastic methods used were able to differentiate subspecies of C. simus and specimens of B. asper, and provide insight into the mechanisms by which the venoms acted on plasma. These methods may be useful in the profiling of similar venoms and perhaps can assist in the assessment of interventions designed to treat envenomation (e.g., antivenom).

  4. Analysis of a cone snail's killer cocktail--the milked venom of Conus geographus.

    PubMed

    Bingham, Jon-Paul; Baker, Margaret R; Chun, Joycelyn B

    2012-11-01

    "Snails can kill" is a statement that receives much disbelief. Yet the venom from Conus geographus, as delivered by a disposable hypodermic-like needle, has indeed killed many unsuspecting human victims. Our understanding of their milked venom the essence of these fatalities, is in itself non-existent. Here, we present the molecular mass analysis of the milked venom of C. geographus, providing the first insight into the composition of its deadly cocktail.

  5. Venoms of Heteropteran Insects: A Treasure Trove of Diverse Pharmacological Toolkits

    PubMed Central

    Walker, Andrew A.; Weirauch, Christiane; Fry, Bryan G.; King, Glenn F.

    2016-01-01

    The piercing-sucking mouthparts of the true bugs (Insecta: Hemiptera: Heteroptera) have allowed diversification from a plant-feeding ancestor into a wide range of trophic strategies that include predation and blood-feeding. Crucial to the success of each of these strategies is the injection of venom. Here we review the current state of knowledge with regard to heteropteran venoms. Predaceous species produce venoms that induce rapid paralysis and liquefaction. These venoms are powerfully insecticidal, and may cause paralysis or death when injected into vertebrates. Disulfide-rich peptides, bioactive phospholipids, small molecules such as N,N-dimethylaniline and 1,2,5-trithiepane, and toxic enzymes such as phospholipase A2, have been reported in predatory venoms. However, the detailed composition and molecular targets of predatory venoms are largely unknown. In contrast, recent research into blood-feeding heteropterans has revealed the structure and function of many protein and non-protein components that facilitate acquisition of blood meals. Blood-feeding venoms lack paralytic or liquefying activity but instead are cocktails of pharmacological modulators that disable the host haemostatic systems simultaneously at multiple points. The multiple ways venom is used by heteropterans suggests that further study will reveal heteropteran venom components with a wide range of bioactivities that may be recruited for use as bioinsecticides, human therapeutics, and pharmacological tools. PMID:26907342

  6. Venoms of Heteropteran Insects: A Treasure Trove of Diverse Pharmacological Toolkits.

    PubMed

    Walker, Andrew A; Weirauch, Christiane; Fry, Bryan G; King, Glenn F

    2016-02-12

    The piercing-sucking mouthparts of the true bugs (Insecta: Hemiptera: Heteroptera) have allowed diversification from a plant-feeding ancestor into a wide range of trophic strategies that include predation and blood-feeding. Crucial to the success of each of these strategies is the injection of venom. Here we review the current state of knowledge with regard to heteropteran venoms. Predaceous species produce venoms that induce rapid paralysis and liquefaction. These venoms are powerfully insecticidal, and may cause paralysis or death when injected into vertebrates. Disulfide-rich peptides, bioactive phospholipids, small molecules such as N,N-dimethylaniline and 1,2,5-trithiepane, and toxic enzymes such as phospholipase A2, have been reported in predatory venoms. However, the detailed composition and molecular targets of predatory venoms are largely unknown. In contrast, recent research into blood-feeding heteropterans has revealed the structure and function of many protein and non-protein components that facilitate acquisition of blood meals. Blood-feeding venoms lack paralytic or liquefying activity but instead are cocktails of pharmacological modulators that disable the host haemostatic systems simultaneously at multiple points. The multiple ways venom is used by heteropterans suggests that further study will reveal heteropteran venom components with a wide range of bioactivities that may be recruited for use as bioinsecticides, human therapeutics, and pharmacological tools.

  7. Functional proteomic analyses of Bothrops atrox venom reveals phenotypes associated with habitat variation in the Amazon.

    PubMed

    Sousa, Leijiane F; Portes-Junior, José A; Nicolau, Carolina A; Bernardoni, Juliana L; Nishiyama-Jr, Milton Y; Amazonas, Diana R; Freitas-de-Sousa, Luciana A; Mourão, Rosa Hv; Chalkidis, Hipócrates M; Valente, Richard H; Moura-da-Silva, Ana M

    2017-03-06

    Venom variability is commonly reported for venomous snakes including Bothrops atrox. Here, we compared the composition of venoms from B. atrox snakes collected at Amazonian conserved habitats (terra-firme upland forest and várzea) and human modified areas (pasture and degraded areas). Venom samples were submitted to shotgun proteomic analysis as a whole or compared after fractionation by reversed-phase chromatography. Whole venom proteomes revealed a similar composition among the venoms with predominance of SVMPs, CTLs, and SVSPs and intermediate amounts of PLA2s and LAAOs. However, when distribution of particular isoforms was analyzed by either method, the venom from várzea snakes showed a decrease in hemorrhagic SVMPs and an increase in SVSPs, and procoagulant SVMPs and PLA2s. These differences were validated by experimental approaches including both enzymatic and in vivo assays, and indicated restrictions in respect to antivenom efficacy to variable components. Thus, proteomic analysis at the isoform level combined to in silico prediction of functional properties may indicate venom biological activity. These results also suggest that the prevalence of functionally distinct isoforms contributes to the variability of the venoms and could reflect the adaptation of B. atrox to distinct prey communities in different Amazon habitats.

  8. Biological and Enzymatic Characterization of Proteases from Crude Venom of the Ant Odontomachus bauri

    PubMed Central

    Silva, Mariana Ferreira; Mota, Caroline Martins; Miranda, Vanessa dos Santos; de Oliveira Cunha, Amanda; Silva, Maraísa Cristina; Naves, Karinne Spirandelli Carvalho; de Oliveira, Fábio; Silva, Deise Aparecida de Oliveira; Mineo, Tiago Wilson Patriarca; Santiago, Fernanda Maria

    2015-01-01

    Hymenoptera venoms constitute an interesting source of natural toxins that may lead to the development of novel therapeutic agents. The present study investigated the enzymatic and biological characteristics of the crude venom of the ant Odontomachus bauri. Its crude venom presents several protein bands, with higher staining for six proteins with gelatinolytic activity (17, 20, 26, 29, 43 and 48 kDa). The crude venom showed high proteolytic activity on azocasein at optimal pH 8.0 and 37 °C. In the presence of protease inhibitors as aprotinin, leupeptin and EDTA, the azocaseinolytic activity was reduced by 45%, 29% and 9%, respectively, suggesting that the enzymes present in the crude venom belong to the three classes of proteases, with the serine proteases in greater intensity. The crude venom degraded the fibrinogen α-chain faster than the β-chain, while the fibrinogen γ-chain remained unchanged. In biological assays, O. bauri venom showed hemolytic and coagulant activity in vitro, and defibrinating activity in vivo. In addition, the venom showed antimicrobial activity against Staphylococcus aureus and Escherichia coli as well as antiparasitic activity on Toxoplasma gondii infection in vitro. In that sense, this study sheds perspectives for pharmacological applications of O. bauri venom enzymes. PMID:26633501

  9. Defensins and the convergent evolution of platypus and reptile venom genes.

    PubMed

    Whittington, Camilla M; Papenfuss, Anthony T; Bansal, Paramjit; Torres, Allan M; Wong, Emily S W; Deakin, Janine E; Graves, Tina; Alsop, Amber; Schatzkamer, Kyriena; Kremitzki, Colin; Ponting, Chris P; Temple-Smith, Peter; Warren, Wesley C; Kuchel, Philip W; Belov, Katherine

    2008-06-01

    When the platypus (Ornithorhynchus anatinus) was first discovered, it was thought to be a taxidermist's hoax, as it has a blend of mammalian and reptilian features. It is a most remarkable mammal, not only because it lays eggs but also because it is venomous. Rather than delivering venom through a bite, as do snakes and shrews, male platypuses have venomous spurs on each hind leg. The platypus genome sequence provides a unique opportunity to unravel the evolutionary history of many of these interesting features. While searching the platypus genome for the sequences of antimicrobial defensin genes, we identified three Ornithorhynchus venom defensin-like peptide (OvDLP) genes, which produce the major components of platypus venom. We show that gene duplication and subsequent functional diversification of beta-defensins gave rise to these platypus OvDLPs. The OvDLP genes are located adjacent to the beta-defensins and share similar gene organization and peptide structures. Intriguingly, some species of snakes and lizards also produce venoms containing similar molecules called crotamines and crotamine-like peptides. This led us to trace the evolutionary origins of other components of platypus and reptile venom. Here we show that several venom components have evolved separately in the platypus and reptiles. Convergent evolution has repeatedly selected genes coding for proteins containing specific structural motifs as templates for venom molecules.

  10. Comparison of total protein and phospholipase A(2) levels in individual coralsnake venoms.

    PubMed

    Kopper, Randall A; Harper, George R; Zimmerman, Sloane; Hook, Jessica

    2013-12-15

    Studies of differences or changes in venom protein levels or enzymatic activities have significance only if contrasted to the normal variations between individual snakes. This study involves the analysis and comparison of venom from 13 individual Texas coralsnakes (Micrurus tener tener) in order to detect differences in the volume, total protein concentration, electrophoretic profile, and PLA2 enzyme activity. A significant inverse correlation between venom volume and total protein concentration was found. Although the 13 venoms were indistinguishable from their electrophoretic protein profiles, phospholipase A2 enzymatic activities varied considerably.

  11. Biological and Pathological Studies of Rosmarinic Acid as an Inhibitor of Hemorrhagic Trimeresurus flavoviridis (habu) Venom

    PubMed Central

    Aung, Hnin Thanda; Nikai, Toshiaki; Komori, Yumiko; Nonogaki, Tsunemasa; Niwa, Masatake; Takaya, Yoshiaki

    2010-01-01

    In our previous report, rosmarinic acid (RA) was revealed to be an antidote active compound in Argusia argentea (family: Boraginaceae). The plant is locally used in Okinawa in Japan as an antidote for poisoning from snake venom, Trimeresurus flavoviridis (habu). This article presents mechanistic evidence of RA’s neutralization of the hemorrhagic effects of snake venom. Anti-hemorrhagic activity was assayed by using several kinds of snake venom. Inhibition against fibrinogen hydrolytic and collagen hydrolytic activities of T. flavoviridis venom were examined by SDS-PAGE. A histopathological study was done by microscopy after administration of venom in the presence or absence of RA. RA was found to markedly neutralize venom-induced hemorrhage, fibrinogenolysis, cytotoxicity and digestion of type IV collagen activity. Moreover, RA inhibited both hemorrhage and neutrophil infiltrations caused by T. flavoviridis venom in pathology sections. These results demonstrate that RA inhibited most of the hemorrhage effects of venom. These findings indicate that rosmarinic acid can be expected to provide therapeutic benefits in neutralization of snake venom accompanied by heat stability. PMID:22069562

  12. Assessment of the Antimicrobial Activity of Few Saudi Arabian Snake Venoms

    PubMed Central

    Al-Asmari, Abdulrahman K.; Abbasmanthiri, Rajamohamed; Abdo Osman, Nasreddien M.; Siddiqui, Yunus; Al-Bannah, Faisal Ahmed; Al-Rawi, Abdulgadir M.; Al-Asmari, Sarah A.

    2015-01-01

    Background Venoms of two cobras, four vipers, a standard antibiotic and an antimycotic, were evaluated comparatively, as antimicrobials. Methods: Six venom concentrations and three of the standard antibiotic and the antimycotic were run in micro-dilution and diffusion plates against the microorganisms. RESULTS: Echis pyramidum, Echis coloratus and Cerastes cerastes gasperettii highest venom concentrations gave significant growth inhibition zones (GIZ) with respect to a negative control, except Bitis arietans, whose concentrations were significant. The cobra Walterinnesia aegyptia had significant venom concentrations more than Naja haje arabica. The Staphylococcus aureus Methicillin Resistant (MRSA) bacterium was the most susceptible, with a highly (P < 0.001) significant GIZ mean difference followed by the Gram positive Staphylococcus aureus, (P < 0.001), Escherichia coli (P < 0.001), Enterococcus faecalis (P < 0.001) and Pseudomonas aeruginosa which, had the least significance (P < 0.05). The fungus Candida albicans was resistant to both viper and cobra venoms (P > 0.05). The antibiotic Vancomycin was more effective than snake venoms though, they were more efficient in inhibiting growth of the resistant Pseudomonas aeruginosa. This antibiotic was also inactive against the fungus, whilst its specific antifungal Fungizone was highly efficient with no antibacterial activity. Conclusions: These findings showed that snake venoms had antibacterial activity comparable to antibiotics, with a directly proportional relationship of venom concentration and GIZ, though, they were more efficient in combatting resistant types of bacteria. Both venoms and the standard antibiotic, showed no antifungal benefits. PMID:26668657

  13. Biological and Enzymatic Characterization of Proteases from Crude Venom of the Ant Odontomachus bauri.

    PubMed

    Silva, Mariana Ferreira; Mota, Caroline Martins; Miranda, Vanessa dos Santos; Cunha, Amanda de Oliveira; Silva, Maraísa Cristina; Naves, Karinne Spirandelli Carvalho; de Oliveira, Fábio; Silva, Deise Aparecida de Oliveira; Mineo, Tiago Wilson Patriarca; Santiago, Fernanda Maria

    2015-11-30

    Hymenoptera venoms constitute an interesting source of natural toxins that may lead to the development of novel therapeutic agents. The present study investigated the enzymatic and biological characteristics of the crude venom of the ant Odontomachus bauri. Its crude venom presents several protein bands, with higher staining for six proteins with gelatinolytic activity (17, 20, 26, 29, 43 and 48 kDa). The crude venom showed high proteolytic activity on azocasein at optimal pH 8.0 and 37 °C. In the presence of protease inhibitors as aprotinin, leupeptin and EDTA, the azocaseinolytic activity was reduced by 45%, 29% and 9%, respectively, suggesting that the enzymes present in the crude venom belong to the three classes of proteases, with the serine proteases in greater intensity. The crude venom degraded the fibrinogen α-chain faster than the β-chain, while the fibrinogen γ-chain remained unchanged. In biological assays, O. bauri venom showed hemolytic and coagulant activity in vitro, and defibrinating activity in vivo. In addition, the venom showed antimicrobial activity against Staphylococcus aureus and Escherichia coli as well as antiparasitic activity on Toxoplasma gondii infection in vitro. In that sense, this study sheds perspectives for pharmacological applications of O. bauri venom enzymes.

  14. Epidemiology, diagnosis, and treatment of Hymenoptera venom allergy in mastocytosis patients.

    PubMed

    Niedoszytko, Marek; Bonadonna, Patrizia; Oude Elberink, Joanne N G; Golden, David B K

    2014-05-01

    Hymenoptera venom allergy is a typical IgE-mediated reaction caused by sensitization to 1 or more allergens of the venom, and accounts for 1.5% to 34% of all cases of anaphylaxis. Patients suffering from mastocytosis are more susceptible to the anaphylactic reactions to an insect sting. This article aims to answer the most important clinical questions raised by the diagnosis and treatment of insect venom allergy in mastocytosis patients. Total avoidance of Hymenoptera is not feasible, and there is no preventive pharmacologic treatment available, although venom immunotherapy reduces the risk of subsequent systemic reactions.

  15. 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.

  16. Cone snail milked venom dynamics--a quantitative study of Conus purpurascens.

    PubMed

    Chun, Joycelyn B S; Baker, Margaret R; Kim, Do H; Leroy, Majdouline; Toribo, Priamo; Bingham, Jon-Paul

    2012-07-01

    Milked venom from cone snails represent a novel biological resource with a proven track record for drug discovery. To strengthen this correlation, we undertook a chromatographic and mass spectrometric study of individual milked venoms from Conus purpurascens. Milked venoms demonstrate extensive peptide differentiation amongst individual specimens and during captivity. Individual snails were found to lack a consistent set of described conopeptides, but instead demonstrated the ability to change venom expression, composition and post-translational modification incorporation; all variations contribute to an increase in chemical diversity and prey targeting strategies. Quantitative amino acid analysis revealed that milked venom peptides are expressed at ranges up to 3.51-121.01 μM within single milked venom samples. This provides for a 6.37-20,965 fold-excess of toxin to induce apparent IC₅₀ for individual conopeptides identified in this study. Comparative molecular mass analysis of duct venom, milked venom and radula tooth extracts from single C. purpurascens specimens demonstrated a level of peptide continuity. Numerous highly abundant and unique conopeptides remain to be characterized. This study strengthens the notion that approaches in conopeptide drug lead discovery programs will potentially benefit from a greater understanding of the toxinological nature of the milked venoms of Conus.

  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. The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system.

    PubMed

    Vonk, Freek J; Casewell, Nicholas R; Henkel, Christiaan V; Heimberg, Alysha M; Jansen, Hans J; McCleary, Ryan J R; Kerkkamp, Harald M E; Vos, Rutger A; Guerreiro, Isabel; Calvete, Juan J; Wüster, Wolfgang; Woods, Anthony E; Logan, Jessica M; Harrison, Robert A; Castoe, Todd A; de Koning, A P Jason; Pollock, David D; Yandell, Mark; Calderon, Diego; Renjifo, Camila; Currier, Rachel B; Salgado, David; Pla, Davinia; Sanz, Libia; Hyder, Asad S; Ribeiro, José M C; Arntzen, Jan W; van den Thillart, Guido E E J M; Boetzer, Marten; Pirovano, Walter; Dirks, Ron P; Spaink, Herman P; Duboule, Denis; McGlinn, Edwina; Kini, R Manjunatha; Richardson, Michael K

    2013-12-17

    Snakes are limbless predators, and many species use venom to help overpower relatively large, agile prey. Snake venoms are complex protein mixtures encoded by several multilocus gene families that function synergistically to cause incapacitation. To examine venom evolution, we sequenced and interrogated the genome of a venomous snake, the king cobra (Ophiophagus hannah), and compared it, together with our unique transcriptome, microRNA, and proteome datasets from this species, with data from other vertebrates. In contrast to the platypus, the only other venomous vertebrate with a sequenced genome, we find that snake toxin genes evolve through several distinct co-option mechanisms and exhibit surprisingly variable levels of gene duplication and directional selection that correlate with their functional importance in prey capture. The enigmatic accessory venom gland shows a very different pattern of toxin gene expression from the main venom gland and seems to have recruited toxin-like lectin genes repeatedly for new nontoxic functions. In addition, tissue-specific microRNA analyses suggested the co-option of core genetic regulatory components of the venom secretory system from a pancreatic origin. Although the king cobra is limbless, we recovered coding sequences for all Hox genes involved in amniote limb development, with the exception of Hoxd12. Our results provide a unique view of the origin and evolution of snake venom and reveal multiple genome-level adaptive responses to natural selection in this complex biological weapon system. More generally, they provide insight into mechanisms of protein evolution under strong selection.

  19. Proteomic view of the venom from the fire ant Solenopsis invicta Buren.

    PubMed

    dos Santos Pinto, José R A; Fox, Eduardo G P; Saidemberg, Daniel M; Santos, Lucilene D; da Silva Menegasso, Anally R; Costa-Manso, Eliúde; Machado, Ednildo A; Bueno, Odair C; Palma, Mario S

    2012-09-07

    Fire ants are well-known by their aggressive stinging behavior, causing many stinging incidents of medical importance. The limited availability of fire ant venom for scientific and clinical uses has restricted, up to now, the knowledge about the biochemistry, immunology, and pharmacology of these venoms. For this study, S. invicta venom was obtained commercially and used for proteomic characterization. For this purpose, the combination of gel-based and gel-free proteomic strategies was used to assign the proteomic profile of the venom from the fire ant S. invicta. This experimental approach permitted the identification of 46 proteins, which were organized into four different groups according to their potential role in fire ant venom: true venom components, housekeeping proteins, body muscle proteins, and proteins involved in chemical communication. The active venom components that may not present toxic roles were classified into three subgroups according to their potential functions: self-venom protection, colony asepsis, and chemical communication. Meanwhile, the proteins classified as true toxins, based on their functions after being injected into the victims' bodies by the fire ants, were classified in five other subgroups: proteins influencing the homeostasis of the victims, neurotoxins, proteins that promote venom diffusion, proteins that cause tissue damage/inflammation, and allergens.

  20. 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

  1. Insights into the venom composition of the ectoparasitoid wasp Nasonia vitripennis from bioinformatic and proteomic studies

    PubMed Central

    de Graaf, D. C.; Aerts, M.; Brunain, M.; Desjardins, C. A.; Jacobs, F. J.; Werren, J. H.; Devreese, B.

    2013-01-01

    With the Nasonia vitripennis genome sequences available, we attempted to determine the proteins present in venom by two different approaches. First, we searched for the transcripts of venom proteins by a bioinformatic approach using amino acid sequences of known hymenopteran venom proteins. Second, we performed proteomic analyses of crude N. vitripennis venom removed from the venom reservoir, implementing both an off-line two-dimensional liquid chromatography matrix-assisted laser desorption/ionization time-of-flight (2D-LC-MALDI-TOF) mass spectrometry (MS) and a two-dimensional liquid chromatography electrospray ionization Founer transform ion cyclotron resonance (2D-LC-ESI-FT-ICR) MS setup. This combination of bioinformatic and proteomic studies resulted in an extraordinary richness of identified venom constituents. Moreover, half of the 79 identified proteins were not yet associated with insect venoms: 16 proteins showed similarity only to known proteins from other tissues or secretions, and an additional 23 did not show similarity to any known protein. Serine proteases and their inhibitors were the most represented. Fifteen nonsecretory proteins were also identified by proteomic means and probably represent so-called ‘venom trace elements’. The present study contributes greatly to the understanding of the biological diversity of the venom of parasitoid wasps at the molecular level. PMID:20167014

  2. Characterization of Three Venom Peptides from the Spitting Spider Scytodes thoracica

    PubMed Central

    Ariki, Nathanial K.; Muñoz, Lisa E.; Armitage, Elizabeth L.; Goodstein, Francesca R.; George, Kathryn G.; Smith, Vanessa L.; Vetter, Irina; Herzig, Volker; King, Glenn F.; Loening, Nikolaus M.

    2016-01-01

    We present the solution-state NMR structures and preliminary functional characterizations of three venom peptides identified from the spitting spider Scytodes thoracica. Despite little sequence identity to other venom peptides, structural characterization reveals that these peptides contain an inhibitor cystine knot motif common to many venom peptides. These are the first structures for any peptide or protein from spiders of the Scytodidae family. Many venom peptides target neuronal ion channels or receptors. However, we have not been able to determine the target of these Scytodes peptides so we can only state with certainty the channels and receptors that they do not target. PMID:27227898

  3. NETosis and lack of DNase activity are key factors in Echis carinatus venom-induced tissue destruction

    PubMed Central

    Katkar, Gajanan D.; Sundaram, Mahalingam S.; NaveenKumar, Somanathapura K.; Swethakumar, Basavarajaiah; Sharma, Rachana D.; Paul, Manoj; Vishalakshi, Gopalapura J.; Devaraja, Sannaningaiah; Girish, Kesturu S.; Kemparaju, Kempaiah

    2016-01-01

    Indian Echis carinatus bite causes sustained tissue destruction at the bite site. Neutrophils, the major leukocytes in the early defence process, accumulate at the bite site. Here we show that E. carinatus venom induces neutrophil extracellular trap (NET) formation. The NETs block the blood vessels and entrap the venom toxins at the injection site, promoting tissue destruction. The stability of NETs is attributed to the lack of NETs-degrading DNase activity in E. carinatus venom. In a mouse tail model, mice co-injected with venom and DNase 1, and neutropenic mice injected with the venom, do not develop NETs, venom accumulation and tissue destruction at the injected site. Strikingly, venom-induced mice tail tissue destruction is also prevented by the subsequent injection of DNase 1. Thus, our study suggests that DNase 1 treatment may have a therapeutic potential for preventing the tissue destruction caused by snake venom. PMID:27093631

  4. In vitro snake venom detoxifying action of some marine algae of Gulf of Mannar, south-east coast of India.

    PubMed

    Vasanthi, Hannah R; Jaswanth, A; Krishnaraj, V; Rajamanickam, G V; Saraswathy, A

    2003-12-01

    The extract of the brown seaweed Padina boergesenii and the red seaweed Hypnea valentiae was found to detoxify (in vitro) the venom of Naja nigricollis. There was a remarkable reduction in the mortality of albino mice after intraperitoneal (i.p.) administration of reconstituted venom with the extract compared to those challenged with the venom only. The survival of the animals exposed to the venom incubated with the different concentrations of the extract was used as the in vitro detoxification parameter.

  5. Scorpion venom peptides with no disulfide bridges: a review.

    PubMed

    Almaaytah, Ammar; Albalas, Qosay

    2014-01-01

    Scorpion venoms are rich sources of biologically active peptides that are classified into disulfide-bridged peptides (DBPs) and non-disulfide-bridged peptides (NDBPs). DBPs are the main scorpion venom components responsible for the neurotoxic effects observed during scorpion envenomation as they usually target membrane bound ion channels of excitable and non-excitable cells. Several hundred DBPs have been identified and functionally characterized in the past two decades. The NDBPs represent a novel group of molecules that have gained great interest only recently due to their high diversity both in their primary structures and bioactivities. This review provides an overview of scorpion NDBPs focusing on their therapeutic applications, modes of discovery, mechanisms of NDBPs genetic diversity and structural properties. It also provides a simple classification for NDBPs that could be adopted and applied to other NDBPs identified in future studies.

  6. Electrophysiological Characterization of the Antarease Metalloprotease from Tityus serrulatus Venom

    PubMed Central

    Zornetta, Irene; Scorzeto, Michele; Mendes Dos Reis, Pablo Victor; De Lima, Maria E.; Montecucco, Cesare; Megighian, Aram; Rossetto, Ornella

    2017-01-01

    Scorpions are among the oldest venomous living organisms and the family Buthidae is the largest and most medically relevant one. Scorpion venoms include many toxic peptides, but recently, a metalloprotease from Tityus serrulatus called antarease was reported to be capable of cleaving VAMP2, a protein involved in the neuroparalytic syndromes of tetanus and botulism. We have produced antarease and an inactive metalloprotease mutant in a recombinant form and analyzed their enzymatic activity on recombinant VAMP2 in vitro and on mammalian and insect neuromuscular junction. The purified recombinant antarease paralyzed the neuromuscular junctions of mice and of Drosophila melanogaster whilst the mutant was inactive. We were unable to demonstrate any cleavage of VAMP2 under conditions which leads to VAMP proteolysis by botulinum neurotoxin type B. Antarease caused a reduced release probability, mainly due to defects upstream of the synaptic vesicles fusion process. Paired pulse experiments indicate that antarease might proteolytically inactivate a voltage-gated calcium channel. PMID:28264432

  7. Venomous snakebite in Thailand. I: Medically important snakes.

    PubMed

    Chanhome, L; Cox, M J; Wilde, H; Jintakoon, P; Chaiyabutr, N; Sitprija, V

    1998-05-01

    Thailand has an abundance of venomous snakes. Among the neurotoxic family Elapidae, there are three species of the genus Naja (cobras), three of the genus Bungarus (kraits), and the king cobra of the genus Ophiophagus. Other Elapidae snakes in Thailand include sea snakes and Asian coral snakes of the genus Calliophis. They have potent venoms but rarely bite humans. Tissue and hemotoxic snakes are represented by family Viperidae, subfamilies Viperinae and Crotalinae. They remain an occupational hazard for farmers and rubber tappers, causing serious morbidity but only rare deaths, since competent treatment is now widely available throughout Thailand. Purified equine antivenin is manufactured locally for the monocled and Siamese spitting cobras (Naja kaouthia and N. siamensis), king cobra (Ophiophagus hannah), banded krait (Bungarus fasciatus), most green pit vipers (Trimeresurus sp.), Malayan pit viper (Calloselasma rhodostoma), and the Siamese Russell's viper (Daboia russelli siamensis).

  8. Intraspecific variation in the Egyptian scorpion Scorpio maurus palmatus venom collected from different biotopes.

    PubMed

    Abdel-Rahman, Mohamed A; Omran, Mohamed Alaa A; Abdel-Nabi, Ismail M; Ueda, Hitoshi; McVean, Alistair

    2009-03-01

    The present study was conducted to explore the following hypotheses: (i) do scorpions (Scorpio maurus palmatus) from different biotopes exhibit intraspecific diversity in their venom? (ii) if so, is this variation associated with ecological or genetic factors, geographical distance, and/or multiple interrelated parameters? To address these questions, scorpions were collected from four geographically isolated localities in Egypt. Three of these locations are from mutually isolated pockets in the arid biotope of Southern Sinai (Wadi Sahab, El-Agramia and Rahaba plains). The fourth population was sampled from the semiarid biotope of Western Mediterranean Costal Desert (WMCD). Using reducing gel electrophoresis (SDS-PAGE), we have shown biotope-specific variation in the expression of peptides from scorpions collected from these distinct areas. WMCD sourced venom samples contain higher molecular weight protein components (219, 200, 170, 139, 116 kDa) than Southern Sinai scorpion venom samples. The Southern Sinai venom is characterized by the presence of 11 protein bands (93-0.58 kDa) that are not mirrored in the individual venom samples of WMCD. Bands of 33 and 3.4 kDa were characteristics of all individual venom samples of the scorpion populations. Even within Southern Sinai area, Sahab venom contains five fractions that are not detected in both El-Agramia and Rahaba venom samples. Moreover, male and female venom analysis revealed some sex-related proteomic similarities and differences between scorpion populations. Female venom appears to be more complicated than the male venom. Female venom samples showed bands of 219, 200, 77.5, 55.5, 45, 39, 37, 24 and 16 kDa which were absent in the male venom. The random amplified polymorphic DNA (RAPD) technique was used to estimate the genetic distance between the four scorpion populations. The RAPD data confirmed the genetic diversity at molecular level among the sampled populations. More than 77 RAPD bands (ranging in size

  9. A Transcriptomic View of the Proteome Variability of Newborn and Adult Bothrops jararaca Snake Venoms

    PubMed Central

    Zelanis, André; Andrade-Silva, Débora; Rocha, Marisa M.; Furtado, Maria F.; Serrano, Solange M. T.; Junqueira-de-Azevedo, Inácio L. M.; Ho, Paulo Lee

    2012-01-01

    Background Snake bite is a neglected public health problem in communities in rural areas of several countries. Bothrops jararaca causes many snake bites in Brazil and previous studies have demonstrated that the pharmacological activities displayed by its venom undergo a significant ontogenetic shift. Similarly, the venom proteome of B. jararaca exhibits a considerable variation upon neonate to adult transition, which is associated with changes in diet from ectothermic prey in early life to endothermic prey in adulthood. Moreover, it has been shown that the Brazilian commercial antibothropic antivenom, which is produced by immunization with adult venom, is less effective in neutralizing newborn venom effects. On the other hand, venom gland transcripts of newborn snakes are poorly known since all transcriptomic studies have been carried out using mRNA from adult specimens. Methods/Principal Findings Here we analyzed venom gland cDNA libraries of newborn and adult B. jararaca in order to evaluate whether the variability demonstrated for its venom proteome and pharmacological activities was correlated with differences in the structure of toxin transcripts. The analysis revealed that the variability in B. jararaca venom gland transcriptomes is quantitative, as illustrated by the very high content of metalloproteinases in the newborn venom glands. Moreover, the variability is also characterized by the structural diversity of SVMP precursors found in newborn and adult transcriptomes. In the adult transcriptome, however, the content of metalloproteinase precursors considerably diminishes and the number of transcripts of serine proteinases, C-type lectins and bradykinin-potentiating peptides increase. Moreover, the comparison of the content of ESTs encoding toxins in adult male and female venom glands showed some gender-related differences. Conclusions/Significance We demonstrate a substantial shift in toxin transcripts upon snake development and a marked decrease in the

  10. 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

  11. Understanding Biological Roles of Venoms Among the Caenophidia: The Importance of Rear-Fanged Snakes.

    PubMed

    Mackessy, Stephen P; Saviola, Anthony J

    2016-11-01

    Snake venoms represent an adaptive trophic response to the challenges confronting a limbless predator for overcoming combative prey, and this chemical means of subduing prey shows several dominant phenotypes. Many front-fanged snakes, particularly vipers, feed on various vertebrate and invertebrate prey species, and some of their venom components (e.g., metalloproteinases, cobratoxin) appear to have been selected for "broad-brush" incapacitation of different prey taxa. Using proteomic and genomic techniques, the compositional diversity of front-fanged snakes is becoming well characterized; however, this is not the case for most rear-fanged colubroid snakes. Because these species consume a high diversity of prey, and because venoms are primarily a trophic adaptation, important clues for understanding specific selective pressures favoring venom component composition will be found among rear-fanged snake venoms. Rear-fanged snakes typically (but not always) produce venoms with lower complexity than front-fanged snakes, and there are even fewer dominant (and, arguably, biologically most relevant) venom protein families. We have demonstrated taxon-specific toxic effects, where lizards and birds show high susceptibility while mammals are largely unaffected, for both Old World and New World rear-fanged snakes, strongly indicating a causal link between toxin evolution and prey preference. New data are presented on myotoxin a, showing that the extremely rapid paralysis induced by this rattlesnake toxin is specific for rodents, and that myotoxin a is ineffectual against lizards. Relatively few rear-fanged snake venoms have been characterized, and basic natural history data are largely lacking, but directed sampling of specialized species indicates that novel compounds are likely among these specialists, particularly among those species feeding on invertebrate prey such as scorpions and centipedes. Because many of the more than 2200 species of colubroid snakes are rear

  12. Comparison of venoms from wild and long-term captive Bothrops atrox snakes and characterization of Batroxrhagin, the predominant class PIII metalloproteinase from the venom of this species.

    PubMed

    Freitas-de-Sousa, L A; Amazonas, D R; Sousa, L F; Sant'Anna, S S; Nishiyama, M Y; Serrano, S M T; Junqueira-de-Azevedo, I L M; Chalkidis, H M; Moura-da-Silva, A M; Mourão, R H V

    2015-11-01

    Comparisons between venoms from snakes kept under captivity or collected at the natural environment are of fundamental importance in order to obtain effective antivenoms to treat human victims of snakebites. In this study, we compared composition and biological activities of Bothrops atrox venom from snakes collected at Tapajós National Forest (Pará State, Brazil) or maintained for more than 10 years under captivity at Instituto Butantan herpetarium after have been collected mostly at Maranhão State, Brazil. Venoms from captive or wild snakes were similar except for small quantitative differences detected in peaks correspondent to phospholipases A2 (PLA2), snake venom metalloproteinases (SVMP) class PI and serine proteinases (SVSP), which did not correlate with fibrinolytic and coagulant activities (induced by PI-SVMPs and SVSPs). In both pools, the major toxic component corresponded to PIII-SVMPs, which were isolated and characterized. The characterization by mass spectrometry of both samples identified peptides that matched with a single PIII-SVMP cDNA characterized by transcriptomics, named Batroxrhagin. Sequence alignments show a strong similarity between Batroxrhagin and Jararhagin (96%). Batroxrhagin samples isolated from venoms of wild or captive snakes were not pro-coagulant, but inhibited collagen-induced platelet-aggregation, and induced hemorrhage and fibrin lysis with similar doses. Results suggest that in spite of environmental differences, venom variability was detected only among the less abundant components. In opposition, the most abundant toxin, which is a PIII-SVMP related to the key effects of the venom, is structurally conserved in the venoms. This observation is relevant for explaining the efficacy of antivenoms produced with venoms from captive snakes in human accidents inflicted at distinct natural environments.

  13. The chromatographic behaviour of wasp venom kinin, kallidin and bradykinin.

    PubMed

    MATHIAS, A P; SCHACHTER, M

    1958-09-01

    Wasp venom kinin which has hitherto appeared to be homogeneous can be resolved by ionexchange chromatography into a single major and two minor components. These are indistinguishable by their action on smooth muscle and by their rapid inactivation by chymotrypsin. All three components of wasp kinin are chromatographically different from kallidin or bradykinin. The close similarity of the latter compounds is confirmed by their identical behaviour on an ion-exchange resin.

  14. Snake Venom Components and Their Cross Reactivity: A Short Review

    DTIC Science & Technology

    1988-10-01

    PLA 2), L-amino acid oxidase, and phosphodiesterase. PLA2 is a protein of approximately 14000 molecular weight, which hydrolizes phosphatidylcholine...to lysophosphatidylcholine and a fatty acid (22). This activity causes the destruction of cell membranes, leading to hemolysis. In the last decade...flavoviridis, Bothrops asper, Pseudoechis australis, and Enhydrina schistosa (20, 33, 42, 43, 54 56). L-amino acid oxidase is detected in venomous snakes

  15. Bibliography of Venomous and Poisonous Marine Animals and Their Toxins

    DTIC Science & Technology

    1984-02-01

    color printing, that when reproduced in Black and White, may change detail of the original copy. 19. Arthropoda Venomous fishes Bryozoa Sea snakes... BRYOZOA = 3730-Y•17 , ......................... 206 ." S’ •d o,XI..•A •dqAKESt 6316.4•7!14 ............................................ 341 "• "dXIL...cation par les moules. Schweiz. - m~d. Wschr. 107, 226, 1977. 205 CHAPTER Vi ll PLATYHELMINTHES, NEMERTEA, ANNELIDA, ARTHROPODS, AND BRYOZOA :: The phylum

  16. Venomous spiders, snakes, and scorpions in the United States.

    PubMed

    Holve, Steve

    2009-04-01

    Venomous bites and stings are complex poisonings that have local and systemic effects. Mild envenomations can be treated with supportive care. Severe envenomations can be treated definitively with species-specific antivenom, although the use of these products has potential risk of immediate and a more delayed onset form of hypersensitivity reactions. Consultation with a toxicologist is recommended to help guide therapy. Field treatments such as tourniquets and incision likely cause more harm than benefit and should be avoided.

  17. Snake venom toxins. The amino acid sequence of toxin Vi2, a homologue of pancreatic trypsin inhibitor, from Dendroaspis polylepis polylepis (black mamba) venom.

    PubMed

    Strydom, D J

    1977-04-25

    The amino acid sequence of venom component Vi2, a protein of low toxicity from Dendroaspis polylepis polylepis venom was determined by automatic sequence analysis in combination with sequence studies on tryptic peptides. This protein, the most retarded fraction of this venom on a cation-exchange resin, is a homologue of bovine pancreatic trypsin inhibitor consisting of a single chain of 57 amino acid residues containing six half-cystine residues. The active site lysyl residue of bovine trypsin inhibitor is conserved in Vi2 although large differences are found in the rest of the molecule.

  18. Scorpions from Mexico: From Species Diversity to Venom Complexity

    PubMed Central

    Santibáñez-López, Carlos E.; Francke, Oscar F.; Ureta, Carolina; Possani, Lourival D.

    2015-01-01

    Scorpions are among the oldest terrestrial arthropods, which are distributed worldwide, except for Antarctica and some Pacific islands. Scorpion envenomation represents a public health problem in several parts of the world. Mexico harbors the highest diversity of scorpions in the world, including some of the world’s medically important scorpion species. The systematics and diversity of Mexican scorpion fauna has not been revised in the past decade; and due to recent and exhaustive collection efforts as part of different ongoing major revisionary systematic projects, our understanding of this diversity has changed compared with previous assessments. Given the presence of several medically important scorpion species, the study of their venom in the country is also important. In the present contribution, the diversity of scorpion species in Mexico is revised and updated based on several new systematic contributions; 281 different species are recorded. Commentaries on recent venomic, ecological and behavioral studies of Mexican scorpions are also provided. A list containing the most important peptides identified from 16 different species is included. A graphical representation of the different types of components found in these venoms is also revised. A map with hotspots showing the current knowledge on scorpion distribution and areas explored in Mexico is also provided. PMID:26712787

  19. Scorpions from Mexico: From Species Diversity to Venom Complexity.

    PubMed

    Santibáñez-López, Carlos E; Francke, Oscar F; Ureta, Carolina; Possani, Lourival D

    2015-12-24

    Scorpions are among the oldest terrestrial arthropods, which are distributed worldwide, except for Antarctica and some Pacific islands. Scorpion envenomation represents a public health problem in several parts of the world. Mexico harbors the highest diversity of scorpions in the world, including some of the world's medically important scorpion species. The systematics and diversity of Mexican scorpion fauna has not been revised in the past decade; and due to recent and exhaustive collection efforts as part of different ongoing major revisionary systematic projects, our understanding of this diversity has changed compared with previous assessments. Given the presence of several medically important scorpion species, the study of their venom in the country is also important. In the present contribution, the diversity of scorpion species in Mexico is revised and updated based on several new systematic contributions; 281 different species are recorded. Commentaries on recent venomic, ecological and behavioral studies of Mexican scorpions are also provided. A list containing the most important peptides identified from 16 different species is included. A graphical representation of the different types of components found in these venoms is also revised. A map with hotspots showing the current knowledge on scorpion distribution and areas explored in Mexico is also provided.

  20. Linear antimicrobial peptides from Ectatomma quadridens ant venom.

    PubMed

    Pluzhnikov, Kirill A; Kozlov, Sergey A; Vassilevski, Alexander A; Vorontsova, Olga V; Feofanov, Alexei V; Grishin, Eugene V

    2014-12-01

    Venoms from three poneromorph ant species (Paraponera clavata, Ectatomma quadridens and Ectatomma tuberculatum) were investigated for the growth inhibition of Gram-positive and Gram-negative bacteria. It was shown that the venom of E. quadridens and its peptide fraction in particular possess marked antibacterial action. Three linear antimicrobial peptides sharing low similarity to the well-known ponericin peptides were isolated from this ant venom by means of size-exclusion and reversed-phase chromatography. The peptides showed antimicrobial activity at low micromolar concentrations. Their primary structure was established by direct Edman sequencing in combination with mass spectrometry. The most active peptide designated ponericin-Q42 was chemically synthesized. Its secondary structure was investigated in aqueous and membrane-mimicking environment, and the peptide was shown to be partially helical already in water, which is unusual for short linear peptides. Analysis of its activity on different bacterial strains, human erythrocytes and chronic myelogenous leukemia K562 cells revealed that the peptide shows broad spectrum cytolytic activity at micromolar and submicromolar concentrations. Ponericin-Q42 also possesses weak toxic activity on flesh fly larvae with LD50 of ∼105 μg/g.

  1. Snake venom toxins. Purification and properties of low-molecular-weight polypeptides of Dendroaspis polylepis polylepis (black mamba) venom.

    PubMed

    Strydom, D J

    1976-10-01

    Twelve low-molecular-weight proteins, of which eleven have subcutaneous LD50 values of less than 40 mug/g mouse, were purified from Dendroaspis polylepis polylepis venom. Ion-exchange chromatography on Amberlite CG-50 and ion-exchange chromatography on carboxymethyl-cellulose and/or phosphocellulose was used for the purification. The amino-terminal sequences of these proteins were determined and used to indicate that five groups of low-molecular-weight polypeptides are to be found in black mamba venom. Proteins from two of these groups which have low toxicity individually, when used together show synergism, in that their toxicity in combination is greater than the sum of their individual toxicities.

  2. Snake venoms. The amino-acid sequence of trypsin inhibitor E of Dendroaspis polylepis polylepis (Black Mamba) venom.

    PubMed

    Joubert, F J; Strydom, D J

    1978-06-01

    Trypsin inhibitor E from black mamba venom comprises 59 amino acid residues in a single polypeptide chain, cross-linked by three intrachain disulphide bridges. The complete primary structure of inhibitor E was elucidated. The sequence is homologous with trypsin inhibitors from different sources. Unique among this homologous series of proteinase inhibitors, inhibitor E has an affinity for transition metal ions, exemplified here by Cu2 and Co2+.

  3. Tentacle Transcriptome and Venom Proteome of the Pacific Sea Nettle, Chrysaora fuscescens (Cnidaria: Scyphozoa)

    PubMed Central

    Ponce, Dalia; Brinkman, Diane L.; Potriquet, Jeremy; Mulvenna, Jason

    2016-01-01

    Jellyfish venoms are rich sources of toxins designed to capture prey or deter predators, but they can also elicit harmful effects in humans. In this study, an integrated transcriptomic and proteomic approach was used to identify putative toxins and their potential role in the venom of the scyphozoan jellyfish Chrysaora fuscescens. A de novo tentacle transcriptome, containing more than 23,000 contigs, was constructed and used in proteomic analysis of C. fuscescens venom to identify potential toxins. From a total of 163 proteins identified in the venom proteome, 27 were classified as putative toxins and grouped into six protein families: proteinases, venom allergens, C-type lectins, pore-forming toxins, glycoside hydrolases and enzyme inhibitors. Other putative toxins identified in the transcriptome, but not the proteome, included additional proteinases as well as lipases and deoxyribonucleases. Sequence analysis also revealed the presence of ShKT domains in two putative venom proteins from the proteome and an additional 15 from the transcriptome, suggesting potential ion channel blockade or modulatory activities. Comparison of these potential toxins to those from other cnidarians provided insight into their possible roles in C. fuscescens venom and an overview of the diversity of potential toxin families in cnidarian venoms. PMID:27058558

  4. Modulation of nicotinic acetylcholine and N-methyl-d-aspartate receptors by some Hymenopteran venoms.

    PubMed

    Zalat, Samy; Elbana, Shereen; Rizzoli, Silvio; Schmidt, Justin O; Mellor, Ian R

    2005-09-01

    The effect of 19 venoms from solitary wasps, solitary bees, social wasps and ants were investigated for their effects on nicotinic acetylcholine receptors (nAChR) and ionotropic glutamate receptors (IGRs) of both the N-methyl-d-aspartate (NMDAR) and non-NMDAR type. Whole-cell patch clamp of human muscle TE671 cells was used to study nAChR, and of rat cortical and cerebellar granule cells for IGRs. Solitary wasp venoms caused significant voltage-dependent antagonism of nAChR responses to 10 microM ACh and NMDAR responses to 100 microM NMDA (+10 microM glycine) when co-applied at 1 microg/ml with the agonists. At positive holding potentials (V(H)) potentiation of these receptors was observed with some venoms. Solitary bee venoms only affected nAChR by causing either voltage-independent antagonism or potentiation of their responses to 10 microM ACh. Of four social wasp venoms, one acted on nAChR by potentiating responses to 10 ACh, while another generated an ACh-like response when applied alone. They had no effect on IGRs. Of the two ant venoms, one caused voltage-independent inhibition of nAChR. Neither affected IGRs. The data indicate the presence of nAChR agonists and antagonists and NMDAR antagonists in Hymenopteran venoms and warrant further investigation to separate and identify these venom components.

  5. [Basophil degranulation test (BDT) as a parameter of hyposensitization with Hymenoptera venoms].

    PubMed

    Dietschi, R; Wüthrich, B; Marti-Wyss, S; Cuhat, J

    1987-10-31

    In a population of 24 insect sting allergy patients undergoing venom immunotherapy the basophil degranulation test (BDT) in the patient sera ("unwashed" BDT) and with washed leukocytes ("washed" BDT) after incubation with bee and wasp (yellow jacket) venom was performed before and during treatment. Venom specific IgE and IgG antibodies, detected by means of RAST, were also monitored. The "unwashed" BDT usually became negative within 6-9 months of beginning immunotherapy, whereas the IgE-RAST was still clearly positive. This was attributed to the blocking influence of the venom specific IgG antibodies induced by the venom therapy. In fact, at this time the BDT with "washed" blood leukocytes, i.e. after elimination of the serum antibodies, was generally still positive. Only during further immunotherapy did cellular sensitization in the "washed" BDT gradually disappear, whereas the IgE-RAST usually turned out weakly positive. A third of the patients showed simultaneously negative results of "unwashed" and "washed" BDT, independently of venom specific IgE and IgG levels. These findings suggest a specific reactivity change of the blood basophils (cellular desensitization) induced by the immunotherapy. The BDT can be used as an immunological parameter for IgG-monitoring of the course of venom immunotherapy and--in addition to skin tests and IgE-RAST--as a further criterion for deciding to stop venom therapy if it turns negative with the washed cells.

  6. Individual venom variability in the South American rattlesnake Crotalus durissus cumanensis.

    PubMed

    Aguilar, Irma; Guerrero, Belsy; Maria Salazar, Ana; Girón, Maria E; Pérez, John C; Sánchez, Elda E; Rodríguez-Acosta, Alexis

    2007-08-01

    Crotalus durissus cumanensis snake venoms from different Venezuelan regions, showed biochemical and hemostatic variations. Fibrino(geno)lytic, hemorrhagic and procoagulant activities and gel-filtration chromatography and SDS-PAGE profiles were analyzed. Differences were observed in fibrinolytic activity: kallikrein-like amidolytic activity was highest in venoms of Santa Teresa, and Margarita. Lagunetica and Carrizales venoms showed the maximum fibrin lysis. The highest hemorrhagic activity was seen in Lagunetica venom. Margarita had the lowest LD(50) of 0.18. Lagunetica, Carrizales and Anzoátegui induced a rapid degradation of fibrinogen alpha chains and slower degradation on beta chains, which could possibly due to a higher content of alpha fibrinogenases in these venoms. This fibrinogenolytic activity is decreased by metalloprotease inhibitors. All venoms, except Carrizales, presented thrombin-like activity. Anzoátegui, Carrizales and Lagunetica, in which fibrinolytic activity was present, showed the largest concentration of high molecular mass components. These results represent a new finding, not previously described, of fibrinolytic activity in South American C. durissus venoms. Santa Teresa and Margarita had fibrinolytic activity, and lack of hemorrhagic activity, representing an important finding in Venezuelan venoms since the description of a fibrinolytic molecule without hemorrhagic activity can have valuable potential in thrombolytic therapy.

  7. [Isolation and partial structural characteristics of major toxic components of Latrodectus pallidus venom].

    PubMed

    Charakha, A R; Shevchenko, L V; Molodkin, A K; Pluzhnikov, K A; Volkova, T M; Grishin, E V

    1997-03-01

    Toxic components of the Latrodectus pallidus spider venom were isolated and characterized. The venom was shown to contain a toxin specific for mammals and at least one insectospecific toxin. Partial amino acid sequences of both toxins were determined, and their high structural homology with previously studied alpha-latrotoxin and alpha-latroinsectotoxin from L. mactans tredecimguttatus was found.

  8. Channel-forming activity in the venom of the cockroach-hunting wasp, Ampulex compressa.

    PubMed

    Gincel, Dan; Haspel, Gal; Libersat, Frederic

    2004-05-01

    The parasitoid solitary wasp Ampulex compressa uses the cockroach Periplaneta americana as a food supply for its larvae. To subdue its prey, the wasp injects a venom cocktail into the brain of the cockroach. We investigated channel activity of A. compressa venom by collecting venom and incorporating it into a planar lipid bilayer. The venom, reconstituted into the bilayer, showed ion channel activity, forming a fast-fluctuating channel with a small conductance of 20+/-0.1pS, with no voltage sensitivity. These channels were not observed when the venom was digested with proteases before application to the bilayer, but were not affected by exposure to protease after their incorporation into the bilayer, indicating that the active venom component is a peptide. The channels were found to be cation selective with similar selectivity for the monovalent cations K(+), Li(+) and Na(+), but showed high selectivity against anions (Cl(-)) and divalent cations (Ca(2+) and Mg(2+)). This study is the first demonstration and biophysical characterization of channel activity in the venom of A. compressa. The possible functional significance of this channel activity is discussed in light of the unusual nature of the effects of this wasp venom on the behavior of its prey.

  9. Proteomic Characterization and Comparison of Malaysian Tropidolaemus wagleri and Cryptelytrops purpureomaculatus Venom Using Shotgun-Proteomics.

    PubMed

    Zainal Abidin, Syafiq Asnawi; Rajadurai, Pathmanathan; Chowdhury, Md Ezharul Hoque; Ahmad Rusmili, Muhamad Rusdi; Othman, Iekhsan; Naidu, Rakesh

    2016-10-18

    Tropidolaemus wagleri and Cryptelytrops purpureomaculatus are venomous pit viper species commonly found in Malaysia. Tandem mass spectrometry analysis of the crude venoms has detected different proteins in T. wagleri and C. purpureomaculatus. They were classified into 13 venom protein families consisting of enzymatic and nonenzymatic proteins. Enzymatic families detected in T. wagleri and C. purpureomaculatus venom were snake venom metalloproteinase, phospholipase A₂, ʟ-amino acid oxidase, serine proteases, 5'-nucleotidase, phosphodiesterase, and phospholipase B. In addition, glutaminyl cyclotransferase was detected in C. purpureomaculatus. C-type lectin-like proteins were common nonenzymatic components in both species. Waglerin was present and unique to T. wagleri-it was not in C. purpureomaculatus venom. In contrast, cysteine-rich secretory protein, bradykinin-potentiating peptide, and C-type natriuretic peptide were present in C. purpureomaculatus venom. Composition of the venom proteome of T. wagleri and C. purpureomaculatus provides useful information to guide production of effective antivenom and identification of proteins with potential therapeutic applications.

  10. Venom yield and its relationship with body size and fang separation of pit vipers from Argentina.

    PubMed

    de Roodt, Adolfo Rafael; Boyer, Leslie Victoria; Lanari, Laura Cecilia; Irazu, Lucia; Laskowicz, Rodrigo Daniel; Sabattini, Paula Leticia; Damin, Carlos Fabián

    2016-10-01

    The amount of venom that a snake can inject is related to its body size. The body size is related to head size and to the distance between fangs. To correlate snake body size, distance between fangs and distance between puncture wounds with the venom yield (and consequently with the venom dose potentially injected in a single snakebite), we studied these variables in two species of public health importance in South America, Bothrops (Rhinocerophis) alternatus, and Crotalus durissus terrificus. In all cases a positive correlation was observed between body length, fang separation distance, distance between puncture wounds and venom yield, with a regression coefficient over 0.5 for Bothrops alternatus and over 0.6 for Crotalus durissus terrificus in all cases, being the relation distance between punctures wounds and venom yield of 0.54 and 0.69 respectively. The difference between fang separation and puncture separation was never greater than 30%, with a mean difference around 13%. The strong relationships between body size, fang separation and venom yield may be useful for planning potential venom production in serpentariums. In addition, because puncture mark separation gives an approximate idea of the size of the snake, this provides a rough idea of the size of the snake that produced a bite and the potential amount of venom that could have been injected.

  11. An in-depth snake venom proteopeptidome characterization: Benchmarking Bothrops jararaca.

    PubMed

    Nicolau, Carolina A; Carvalho, Paulo C; Junqueira-de-Azevedo, Inácio L M; Teixeira-Ferreira, André; Junqueira, Magno; Perales, Jonas; Neves-Ferreira, Ana Gisele C; Valente, Richard H

    2017-01-16

    A large-scale proteomic approach was devised to advance the understanding of venom composition. Bothrops jararaca venom was fractionated by OFFGEL followed by chromatography, generating peptidic and proteic fractions. The latter was submitted to trypsin digestion. Both fractions were separately analyzed by reversed-phase nanochromatography coupled to high resolution mass spectrometry. This strategy allowed deeper and joint characterizations of the peptidome and proteome (proteopeptidome) of this venom. Our results lead to the identification of 46 protein classes (with several uniquely assigned proteins per class) comprising eight high-abundance bona fide venom components, and 38 additional classes in smaller quantities. This last category included previously described B. jararaca venom proteins, common Elapidae venom constituents (cobra venom factor and three-finger toxin), and proteins typically encountered in lysosomes, cellular membranes and blood plasma. Furthermore, this report is the most complete snake venom peptidome described so far, both in number of peptides and in variety of unique proteins that could have originated them. It is hypothesized that such diversity could enclose cryptides, whose bioactivities would contribute to envenomation in yet undetermined ways. Finally, we propose that the broad range screening of B. jararaca peptidome will facilitate the discovery of bioactive molecules, eventually leading to valuable therapeutical agents.

  12. 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.

  13. Using a Novel Ontology to Inform the Discovery of Therapeutic Peptides from Animal Venoms

    PubMed Central

    Romano, Joseph D.; Tatonetti, Nicholas P.

    2016-01-01

    Venoms and venom-derived compounds constitute a rich and largely unexplored source of potentially therapeutic compounds. To facilitate biomedical research, it is necessary to design a robust informatics infrastructure that will allow semantic computation of venom concepts in a standardized, consistent manner. We have designed an ontology of venom-related concepts — named Venom Ontology — that reuses an existing public data source: UniProt’s Tox-Prot database. In addition to describing the ontology and its construction, we have performed three separate case studies demonstrating its utility: (1) An exploration of venom peptide similarity networks within specific genera; (2) A broad overview of the distribution of available data among common taxonomic groups spanning the known tree of life; and (3) An analysis of the distribution of venom complexity across those same taxonomic groups. Venom Ontology is publicly available on BioPortal at http://bioportal.bioontology.org/ontologies/CU-VO. PMID:27570672

  14. "It stings a bit but it cleans well": venoms of Hymenoptera and their antimicrobial potential.

    PubMed

    Moreau, Sébastien J M

    2013-02-01

    Venoms from Hymenoptera display a wide range of functions and biological roles. These notably include manipulation of the host, capture of prey and defense against competitors and predators thanks to endocrine and immune systems disruptors, neurotoxic, cytolytic and pain-inducing venom components. Recent works indicate that many hymenopteran species, whatever their life style, have also evolved a venom with properties which enable it to regulate microbial infections, both in stinging and stung animals. In contrast to biting insects and their salivary glands, stinging Hymenoptera seem to constitute an under-exploited ecological niche for agents of vector-borne disease. Few parasitic or mutualistic microorganisms have been reported to be hosted by venom-producing organs or to be transmitted to stung animals. This may result from the presence of potent antimicrobial molecules in venoms, histological features of venom apparatuses and selective effects of venoms on immune defenses of targeted organisms. The present paper reviews for the first time the venom antimicrobial potential of solitary and social Hymenoptera in molecular, ecological, and evolutionary perspectives.

  15. Proteomic Characterization and Comparison of Malaysian Tropidolaemus wagleri and Cryptelytrops purpureomaculatus Venom Using Shotgun-Proteomics

    PubMed Central

    Zainal Abidin, Syafiq Asnawi; Rajadurai, Pathmanathan; Chowdhury, Md Ezharul Hoque; Ahmad Rusmili, Muhamad Rusdi; Othman, Iekhsan; Naidu, Rakesh

    2016-01-01

    Tropidolaemus wagleri and Cryptelytrops purpureomaculatus are venomous pit viper species commonly found in Malaysia. Tandem mass spectrometry analysis of the crude venoms has detected different proteins in T. wagleri and C. purpureomaculatus. They were classified into 13 venom protein families consisting of enzymatic and nonenzymatic proteins. Enzymatic families detected in T. wagleri and C. purpureomaculatus venom were snake venom metalloproteinase, phospholipase A2, l-amino acid oxidase, serine proteases, 5′-nucleotidase, phosphodiesterase, and phospholipase B. In addition, glutaminyl cyclotransferase was detected in C. purpureomaculatus. C-type lectin-like proteins were common nonenzymatic components in both species. Waglerin was present and unique to T. wagleri—it was not in C. purpureomaculatus venom. In contrast, cysteine-rich secretory protein, bradykinin-potentiating peptide, and C-type natriuretic peptide were present in C. purpureomaculatus venom. Composition of the venom proteome of T. wagleri and C. purpureomaculatus provides useful information to guide production of effective antivenom and identification of proteins with potential therapeutic applications. PMID:27763534

  16. Venom analysis of long-term captive Pakistan cobra (Naja naja) populations.

    PubMed

    Modahl, Cassandra M; Doley, Robin; Kini, R Manjunatha

    2010-01-01

    Venom production facilities keep established colonies of captive snakes to obtain venom for research and antiserum production. Due to strict regulations of importation, some of these colonies are formed with only a small number of initial animals and consist of closely related individuals (sometimes siblings). To understand the effect of long-term captivity on the venom composition and its impact on antiserum production, we analyzed 15 long-term captive Naja naja (Pakistan) originating from two separate venom production colonies using liquid chromatography-mass spectrometry and electrophoresis. The chromatogram produced from each individual cobra venom was found to be different. When the protein molecular masses of the peaks were identified, it was found that all the venoms consisted of the same protein composition, but the concentration of the proteins were different. Although three-finger toxins and phospholipase A(2) enzymes are the major toxic components present in these venoms, there was a clear difference in the amounts of each individual isoform. Such variation may affect the ability of antivenoms in neutralizing the toxic components of the wild type venom.

  17. Tentacle Transcriptome and Venom Proteome of the Pacific Sea Nettle, Chrysaora fuscescens (Cnidaria: Scyphozoa).

    PubMed

    Ponce, Dalia; Brinkman, Diane L; Potriquet, Jeremy; Mulvenna, Jason

    2016-04-05

    Jellyfish venoms are rich sources of toxins designed to capture prey or deter predators, but they can also elicit harmful effects in humans. In this study, an integrated transcriptomic and proteomic approach was used to identify putative toxins and their potential role in the venom of the scyphozoan jellyfish Chrysaora fuscescens. A de novo tentacle transcriptome, containing more than 23,000 contigs, was constructed and used in proteomic analysis of C. fuscescens venom to identify potential toxins. From a total of 163 proteins identified in the venom proteome, 27 were classified as putative toxins and grouped into six protein families: proteinases, venom allergens, C-type lectins, pore-forming toxins, glycoside hydrolases and enzyme inhibitors. Other putative toxins identified in the transcriptome, but not the proteome, included additional proteinases as well as lipases and deoxyribonucleases. Sequence analysis also revealed the presence of ShKT domains in two putative venom proteins from the proteome and an additional 15 from the transcriptome, suggesting potential ion channel blockade or modulatory activities. Comparison of these potential toxins to those from other cnidarians provided insight into their possible roles in C. fuscescens venom and an overview of the diversity of potential toxin families in cnidarian venoms.

  18. 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

  19. Characterization of inflammatory response induced by Potamotrygon motoro stingray venom in mice.

    PubMed

    Kimura, Louise F; Prezotto-Neto, José P; Antoniazzi, Marta M; Jared, Simone Gs; Santoro, Marcelo L; Barbaro, Katia C

    2014-05-01

    Freshwater stingray accidents cause intense pain followed by edema, erythema, and necrosis formation. Treatment for stingray envenomation is based on administration of analgesic, antipyretic, and anti-inflammatory drugs. This report evaluated the local inflammatory reaction-including edema formation, leukocyte recruitment, release of inflammatory mediators, and histopathological changes-after the intraplantar injection of Potamotrygon motoro stingray venom in mice. Edema was observed as soon as 15 min after venom injection, peaking at 30 min, and lasted up to 48 h. In addition, P. motoro venom increased neutrophil counts in the site of injection, at all time periods and venom doses analyzed. Increased eosinophil and lymphocyte counts were detected mainly at 24 h. Moreover, monocytes/macrophages were observed in large amounts at 24 and 48 h. Microscopically, the venom induced leukocyte migration to the injured tissue, edema, mast cell degranulation, angiogenesis, and epidermal damage. Inflammatory mediator release (IL-6, MCP-1 and KC) was detected as soon as 1 h after venom injection, and it increased significantly at 4 h. At 24 h, the venom induced only the production of MCP-1. These results show that this stingray venom evokes a complex inflammatory reaction, with rapid and persistent edema formation, leukocyte recruitment, and release of cytokines and chemokines.

  20. Maturity-related changes in venom toxicity of the freshwater stingray Potamotrygon leopoldi.

    PubMed

    Kirchhoff, Kim N; Klingelhöfer, Ines; Dahse, Hans-Martin; Morlock, Gertrud; Wilke, Thomas

    2014-12-15

    Aquatic venomous animals such as stingrays represent a largely untapped source for venom-based drug development. However, the major challenge for a potential drug development pipeline is the high inter- and intraspecific variability in toxicity and venom composition. As of today, little is known about maturity-driven changes in these traits in stingrays. The present study investigates the differences in toxicity and venom composition in different maturity stages of the freshwater stingray Potamotrygon leopoldi. This species can be found in the Xingú River basin (Brazil), where it mainly feeds on invertebrates, while being predated by other stingrays or large catfishes. P. leopoldi, as commonly known for stingrays, can cause severe injuries with the venomous dentine spine located at its tails. The toxicity of tissue extracts of juvenile and mature specimens was recorded on a myoblast cell culture bioassay. Venom composition and bioactivity of compounds were analyzed with planar chromatography linked to an Aliivibrio fischeri bioassay. Results revealed a decrease in venom toxicity during maturation, but no changes in venom composition. These findings may indicate that toxicity in mature specimens becomes evolutionary less important, probably due to a decrease in predation pressure.

  1. Omega-agatoxin-TK is a useful tool to study P-type Ca2+ channel-mediated changes in internal Ca2+ and glutamate release in depolarised brain nerve terminals.

    PubMed

    Sitges, María; Galindo, Carlos Alberto

    2005-01-01

    The present study shows that omega-agatoxin-TK, a toxin of the venom of Agelenopsis aperta, which is 10 times more concentrated than the P/Q type Ca(2+) channel blocker, omega-agatoxin-IVA in the venom, inhibits the high K(+) depolarisation-induced rise in internal Ca(2+) (Ca(i), as determined with fura-2) dose dependently in cerebral (striatal and hippocampal) isolated nerve endings, with calculated IC(50)'s of about 60nM. The maximal inhibition exerted by omega-agatoxin-TK in striatal synaptosomes (61 +/- 11%) is 10% larger than in hippocampal synaptosomes, suggesting a larger population of omega-agatoxin-TK-sensitive Ca(2+) channels in striatal than in hippocampal nerve endings. The N-type Ca(2+) channel blocker, omega-conotoxin-GVIA (1muM), inhibits part of the omega-agatoxin-TK-insensitive rise in Ca(i) induced by high K(+). In contrast to the inhibition exerted by omega-agatoxin-TK on the Ca(i) response to high K(+), omega-agatoxin-TK failed to inhibit the tetrodotoxin-sensitive elevations in Ca(i) and in internal Na(+) (Na(i), as determined with SBFI) induced by veratridine, indicating that the Ca(2+) influx activated by veratridine does not involve omega-agatoxin-TK-sensitive channels. High K(+) does not increase Na(i). In [(3)H]Glu preloaded hippocampal synaptosomes super-fused with low Na(+) Krebs Ringer HEPES (a condition that guarantees the elimination of neurotransmitter transporters-mediated release), the release of [(3)H]Glu induced by high K(+) is absolutely dependent on the entrance of external Ca(2+). This exocytotic release of [(3)H]Glu attained in the absence of a chemical Na(+) gradient is inhibited with the same potency and efficacy by omega-agatoxin-TK and by omega-agatoxin-IVA, which is known to differ from omega-agatoxin-TK in its amino terminal moiety. These results indicate that omega-agatoxin-TK represents a good pharmacological tool to study P/Q type Ca(2+) channel-mediated responses in cerebral nerve endings.

  2. Production of human antibody fragments binding to melittin and phospholipase A2 in Africanised bee venom: minimising venom toxicity.

    PubMed

    Funayama, Jaqueline C; Pucca, Manuela B; Roncolato, Eduardo C; Bertolini, Thaís B; Campos, Lucas B; Barbosa, José E

    2012-03-01

    The hybrid created from the crossbreeding of European and African bees, known as the Africanised bee, has provided numerous advantages for current beekeeping. However, this new species exhibits undesirable behaviours, such as colony defence instinct and a propensity to attack en masse, which can result in serious accidents. To date, there is no effective treatment for cases of Africanised bee envenomation. One promising technique for developing an efficient antivenom is the use of phage display technology, which enables the production of human antibodies, thus avoiding the complications of serum therapy, such as anaphylaxis and serum sickness. The aim of this study was to produce human monoclonal single-chain Fv (scFv) antibody fragments capable of inhibiting the toxic effects of Africanised bee venom. We conducted four rounds of selection of antibodies against the venom and three rounds of selection of antibodies against purified melittin. Three clones were selected and tested by enzyme-linked immunosorbent assay to verify their specificity for melittin and phospholipase A2. Two clones (C5 and C12) were specific for melittin, and one (A7) was specific for phospholipase A2. In a kinetic haemolytic assay, these clones were evaluated individually and in pairs. The A7-C12 combination had the best synergistic effect and was chosen to be used in the assays of myotoxicity inhibition and lethality. The A7-C12 combination inhibited the in vivo myotoxic effect of the venom and increased the survival of treated animals.

  3. Venom proteins from endoparasitoid wasps and their role in host-parasite interactions.

    PubMed

    Asgari, Sassan; Rivers, David B

    2011-01-01

    Endoparasitoids introduce a variety of factors into their host during oviposition to ensure successful parasitism. These include ovarian and venom fluids that may be accompanied by viruses and virus-like particles. An overwhelming number of venom components are enzymes with similarities to insect metabolic enzymes, suggesting their recruitment for expression in venom glands with modified functions. Other components include protease inhibitors, paralytic factors, and constituents that facilitate/enhance entry and expression of genes from symbiotic viruses or virus-like particles. In addition, the venom gland may itself support replication/production of some viruses or virus-like entities. Overlapping functions and structural similarities of some venom, ovarian, and virus-encoded proteins suggest coevolution of molecules recruited by endoparasitoids to maintain their fitness relative to their host.

  4. Venomous and Poisonous Australian Animals of Veterinary Importance: A Rich Source of Novel Therapeutics

    PubMed Central

    Allavena, Rachel E.

    2014-01-01

    Envenomation and poisoning by terrestrial animals (both vertebrate and invertebrate) are a significant economic problem and health risk for domestic animals in Australia. Australian snakes are some of the most venomous animals in the world and bees, wasps, ants, paralysis ticks, and cane toads are also present as part of the venomous and poisonous fauna. The diagnosis and treatment of envenomation or poisoning in animals is a challenge and can be a traumatic and expensive process for owners. Despite the potency of Australian venoms, there is potential for novel veterinary therapeutics to be modeled on venom toxins, as has been the case with human pharmaceuticals. A comprehensive overview of envenomation and poisoning signs in livestock and companion animals is provided and related to the potential for venom toxins to act as therapeutics. PMID:25143943

  5. Snake Venomics and Antivenomics of Bothrops diporus, a Medically Important Pitviper in Northeastern Argentina

    PubMed Central

    Gay, Carolina; Sanz, Libia; Calvete, Juan J.; Pla, Davinia

    2015-01-01

    Snake species within genus Bothrops are responsible for more than 80% of the snakebites occurring in South America. The species that cause most envenomings in Argentina, B. diporus, is widely distributed throughout the country, but principally found in the Northeast, the region with the highest rates of snakebites. The venom proteome of this medically relevant snake was unveiled using a venomic approach. It comprises toxins belonging to fourteen protein families, being dominated by PI- and PIII-SVMPs, PLA2 molecules, BPP-like peptides, L-amino acid oxidase and serine proteinases. This toxin profile largely explains the characteristic pathophysiological effects of bothropic snakebites observed in patients envenomed by B. diporus. Antivenomic analysis of the SAB antivenom (Instituto Vital Brazil) against the venom of B. diporus showed that this pentabothropic antivenom efficiently recognized all the venom proteins and exhibited poor affinity towards the small peptide (BPPs and tripeptide inhibitors of PIII-SVMPs) components of the venom. PMID:26712790

  6. Comparative analysis of methods for concentrating venom from jellyfish Rhopilema esculentum Kishinouye

    NASA Astrophysics Data System (ADS)

    Li, Cuiping; Yu, Huahua; Feng, Jinhua; Chen, Xiaolin; Li, Pengcheng

    2009-02-01

    In this study, several methods were compared for the efficiency to concentrate venom from the tentacles of jellyfish Rhopilema esculentum Kishinouye. The results show that the methods using either freezing-dry or gel absorption to remove water to concentrate venom are not applicable due to the low concentration of the compounds dissolved. Although the recovery efficiency and the total venom obtained using the dialysis dehydration method are high, some proteins can be lost during the concentrating process. Comparing to the lyophilization method, ultrafiltration is a simple way to concentrate the compounds at high percentage but the hemolytic activities of the proteins obtained by ultrafiltration appear to be lower. Our results suggest that overall lyophilization is the best and recommended method to concentrate venom from the tentacles of jellyfish. It shows not only the high recovery efficiency for the venoms but high hemolytic activities as well.

  7. Detection of venom by enzyme linked immunosorbent assay (ELISA) in patients bitten by snakes in Thailand.

    PubMed Central

    Silamut, K; Ho, M; Looareesuwan, S; Viravan, C; Wuthiekanun, V; Warrell, D A

    1987-01-01

    The ability of an enzyme linked immunosorbent assay (ELISA) to detect venom was evaluated in 251 patients bitten by four of the commonest poisonous snakes in Thailand. Serum was tested only from patients who brought the snakes that had bitten them. About one third of all bitten patients had detectable venom antigenaemia, though a smaller proportion were symptomatic. Serum venom concentrations on admission correlated with the severity of clinical manifestations. The test was sensitive and specific even for specimens that had been collected and stored under suboptimal conditions. The technique is suitable for forensic use in cases of suspected snakebite. The combination of snake identification and venom antigen detection should be a more reliable means of studying the epidemiology of snakebite than the measurement of venom antibodies in a population. PMID:3101897

  8. Processing of Snake Venom Metalloproteinases: Generation of Toxin Diversity and Enzyme Inactivation

    PubMed Central

    Moura-da-Silva, Ana M.; Almeida, Michelle T.; Portes-Junior, José A.; Nicolau, Carolina A.; Gomes-Neto, Francisco; Valente, Richard H.

    2016-01-01

    Snake venom metalloproteinases (SVMPs) are abundant in the venoms of vipers and rattlesnakes, playing important roles for the snake adaptation to different environments, and are related to most of the pathological effects of these venoms in human victims. The effectiveness of SVMPs is greatly due to their functional diversity, targeting important physiological proteins or receptors in different tissues and in the coagulation system. Functional diversity is often related to the genetic diversification of the snake venom. In this review, we discuss some published evidence that posit that processing and post-translational modifications are great contributors for the generation of functional diversity and for maintaining latency or inactivation of enzymes belonging to this relevant family of venom toxins. PMID:27294958

  9. The Protective Effect of Bee Venom on Fibrosis Causing Inflammatory Diseases

    PubMed Central

    Lee, Woo-Ram; Pak, Sok Cheon; Park, Kwan-Kyu

    2015-01-01

    Bee venom therapy is a treatment modality that may be thousands of years old and involves the application of live bee stings to the patient’s skin or, in more recent years, the injection of bee venom into the skin with a hypodermic needle. Studies have proven the effectiveness of bee venom in treating pathological conditions such as arthritis, pain and cancerous tumors. However, there has not been sufficient review to fully elucidate the cellular mechanisms of the anti-inflammatory effects of bee venom and its components. In this respect, the present study reviews current understanding of the mechanisms of the anti-inflammatory properties of bee venom and its components in the treatment of liver fibrosis, atherosclerosis and skin disease. PMID:26580653

  10. Connectivity maps for biosimilar drug discovery in venoms: the case of Gila monster venom and the anti-diabetes drug Byetta®.

    PubMed

    Aramadhaka, Lavakumar Reddy; Prorock, Alyson; Dragulev, Bojan; Bao, Yongde; Fox, Jay W

    2013-07-01

    Like most natural product libraries animal venoms have long been recognized as potentially rich source of biologically active molecules with the potential to be mined for the discovery of drugs, drug leads and/or biosimilars. In this work we demonstrate as a proof of concept a novel approach to explore venoms for potential biosimilarity to other drugs based on their ability to alter the transcriptomes of test cell lines followed by informatic searches and Connectivity Mapping to match the action of the venom on the cell gene expression to that of other drugs in the Connectivity Map (C-Map) database. As our test animal venom we chose Heloderma suspectum venom (Gila monster) since exendin-4, a glucagon-like peptide 1 receptor agonist, isolated from the venom is currently on the market to treat type 2 diabetes. The action of Byetta(®) (exentide, synthetic exendin-4), was also used in transcriptome studies. Analysis of transcriptomes from cells treated with the venom or the drug showed similarities as well as differences. The former case was primarily attributed to the fact that Gila monster venom likely contains a variety of biologically active molecules that could alter the MCF7 cell transcriptome compared to that of the single perturbant Byetta(®). Using Ingenuity Pathway Analysis software, insulin-like growth factor 1 signaling was identified in the category of "Top Canonical Pathways" for both the venom and Byetta(®). In the category of "Top Molecules" up-regulated, both venom and Byetta(®) shared IL-8, cyclic AMP-dependent transcription factor 3 (ATF-3), neuron-derived orphan receptor 1 (NR4A3), dexamethasone-induced Ras-related protein 1 (RASD1) and early growth response protein 1, (EGR-1) all with potential relevance in diabetes. Using Connectivity Mapping, Gila monster venom showed positive correlation with 1732 instances and negative correlation with 793 instances in the Connectivity database whereas Byetta(®) showed positive correlation with 1692

  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. Mad, bad and dangerous to know: the biochemistry, ecology and evolution of slow loris venom

    PubMed Central

    2013-01-01

    Only seven types of mammals are known to be venomous, including slow lorises (Nycticebus spp.). Despite the evolutionary significance of this unique adaptation amongst Nycticebus, the structure and function of slow loris venom is only just beginning to be understood. Here we review what is known about the chemical structure of slow loris venom. Research on a handful of captive samples from three of eight slow loris species reveals that the protein within slow loris venom resembles the disulphide-bridged heterodimeric structure of Fel-d1, more commonly known as cat allergen. In a comparison of N. pygmaeus and N. coucang, 212 and 68 compounds were found, respectively. Venom is activated by combining the oil from the brachial arm gland with saliva, and can cause death in small mammals and anaphylactic shock and death in humans. We examine four hypotheses for the function of slow loris venom. The least evidence is found for the hypothesis that loris venom evolved to kill prey. Although the venom’s primary function in nature seems to be as a defense against parasites and conspecifics, it may also serve to thwart olfactory-orientated predators. Combined with numerous other serpentine features of slow lorises, including extra vertebra in the spine leading to snake-like movement, serpentine aggressive vocalisations, a long dark dorsal stripe and the venom itself, we propose that venom may have evolved to mimic cobras (Naja sp.). During the Miocene when both slow lorises and cobras migrated throughout Southeast Asia, the evolution of venom may have been an adaptive strategy against predators used by slow lorises as a form of Müllerian mimicry with spectacled cobras. PMID:24074353

  13. Species-dependent variations in the in vitro myotoxicity of death adder (Acanthophis) venoms.

    PubMed

    Wickramaratna, Janith C; Fry, Bryan G; Hodgson, Wayne C

    2003-08-01

    Based on early studies on Acanthophis antarcticus (common death adder) venom, it has long been thought that death adder snake venoms are devoid of myotoxicity. However, a recent clinical study reported rhabdomyolysis in patients following death adder envenomations, in Papua New Guinea, by a species thought to be different to A. antarcticus. Subsequently, a myotoxic phospholipase A2 component was isolated from A. rugosus (Irian Jayan death adder) venom. The present study examined the venoms of A. praelongus (northern), A. pyrrhus (desert), A. hawkei (Barkly Tableland), A. wellsi (black head), A. rugosus, A. sp. Seram and the regional variants of A. antarcticus for in vitro myotoxicity. Venoms (10-50 microg/ml) were examined for myotoxicity using the chick directly (0.1 Hz, 2 ms, supramaximal V) stimulated biventer cervicis nerve-muscle preparation. A significant contracture of skeletal muscle and/or inhibition of direct twitches were considered signs of myotoxicity. This was confirmed by histological examination. All venoms displayed high phospholipase A2 activity. The venoms (10-50 microg/ml) of A. sp. Seram, A. praelongus, A. rugosus,and A. wellsi caused a significant inhibition of direct twitches and an increase in baseline tension compared to the vehicle (n=4-6; two-way ANOVA, p<0.05). Furthermore, these venoms caused dose-dependent morphological changes in skeletal muscle. In contrast, the venoms (10-50 microg/ml; n=3-6) of A. hawkei, A. pyrrhus, and regional variants of A. antarcticus were devoid of myotoxicity. Prior incubation (10 min) of CSL death adder antivenom (5 U/ml) prevented the myotoxicity caused by A. sp. Seram, A. praelongus, A. rugosus, and A. wellsi venoms (50 microg/ml; n=4-7). In conclusion, clinicians may need to be mindful of possible myotoxicity following envenomations by A. praelongus, A. rugosus, A. sp. Seram, and A. wellsi species.

  14. Local inflammatory reaction induced by Scolopendra viridicornis centipede venom in mice.

    PubMed

    Kimura, Louise Faggionato; Prezotto-Neto, José Pedro; Távora, Bianca de Carvalho Lins Fernandes; Antoniazzi, Marta Maria; Knysak, Irene; Gióia Guizze, Samuel Paulo; Santoro, Marcelo Larami; Barbaro, Katia Cristina

    2013-12-15

    Centipede envenomation is generally mild, and human victims usually manifest burning pain, erythema and edema. Despite the abundance and ubiquity of these animals, centipede venom has been poorly characterized in literature. For this reason, the aim of this work was to investigate local inflammatory features induced by Scolopendra viridicornis centipede envenomation in mice, evaluating edema formation, leukocyte infiltration, production of inflammatory mediators, and also performing histological analysis. The highest edematogenic activity induced by the venom, determined by plethysmometry, was noticed 0.5 h after injection in mice footpad. At 24 h, edema was still detected in animals that received 15 and 60 μg of venom, and at 48 h, only in animals injected with 60 μg of venom. In relation to leukocyte count, S. viridicornis venom induced cell recruitment, mainly neutrophils and monocytes/macrophages, in all doses and time periods analyzed in comparison with PBS-injected mice. An increase in lymphocytes was detected especially between 1 and 24 h at 60 μg dose. Besides, eosinophil recruitment was observed mainly for 15 and 60 μg doses in early time periods. Edema formation and cell recruitment were also confirmed by histological analysis. Moreover, S. viridicornis venom stimulated the release of IL-6, MCP-1, KC, and IL-1β. Conversely, S. viridicornis venom did not induce the release of detectable levels of TNF-α. We demonstrated that the edematogenic activity induced by S. viridicornis venom was of rapid onset, and the venom stimulated secretion of pro-inflammatory mediators which contribute to the inflammatory reaction induced by S. viridicornis venom in an experimental model.

  15. Involvement of mast cells and histamine in edema induced in mice by Scolopendra viridicornis centipede venom.

    PubMed

    Távora, Bianca C L F; Kimura, Louise F; Antoniazzi, Marta M; Chiariello, Thiago M; Faquim-Mauro, Eliana L; Barbaro, Katia C

    2016-10-01

    Bites caused by Scolopendra viridicornis centipede are mainly characterized by burning pain, paresthesia and edema. On this regard, the aim of this work was to study the involvement of mast cells and histamine in edema induced by Scolopendra viridicornis (Sv) centipede venom. The edema was analyzed on mice paws. The mice were pretreated with cromolyn (mast cell degranulation inhibitor) and antagonists of histamine receptors, such as promethazine (H1R), cimetidine (H2R) and thioperamide (H3/H4R). The analyses were carried out at different times after the injection of Sv venom (15 μg) or PBS in the footpad of mice. Our results showed a significant inhibition of the edema induced by Sv venom injection in mice previously treated: cromolyn (38-91%), promethazine (50-59%) and thioperamide (around 30%). The treatment with cimetidine did not alter the edema induced by Sv venom. Histopathological analysis showed that Sv venom injection (15 μg) induced edema, leukocyte recruitment and mast cells degranulation, when compared with the PBS-injected mice. Direct effects of the Sv venom on mast cells were studied in PT-18 line (mouse mast cell) and RBL-2H3 cells (rat mast cells). The data showed that higher doses (3.8 and 7.5 μg) of Sv venom were cytotoxic for both cell lineages and induced morphological changes. However, lower doses of the venom induced degranulation of both mast cell lines, as well as the secretion of MCP-1, IL-6 and IL-1β. The production of PGD2 was only observed in the RBL-2H3 line incubated with Sv venom. Taking our results together, we demonstrated that upon Sv venom exposure, mast cells and histamine are crucial for the establishment of the local inflammatory reaction.

  16. Cytotoxicity and hemolytic activity of jellyfish Nemopilema nomurai (Scyphozoa: Rhizostomeae) venom.

    PubMed

    Kang, Changkeun; Munawir, Al; Cha, Mijin; Sohn, Eun-Tae; Lee, Hyunkyoung; Kim, Jong-Shu; Yoon, Won Duk; Lim, Donghyun; Kim, Euikyung

    2009-07-01

    The recent bloom of a giant jellyfish Nemopilema nomurai has caused a danger to sea bathers and fishery damages in the waters of China, Korea, and Japan. The present study investigated the cytotoxic and hemolytic activities of crude venom extract of N. nomurai using a number of in vitro assays. The jellyfish venom showed a much higher cytotoxic activity in H9C2 heart myoblast than in C2C12 skeletal myoblast (LC(50)=2 microg/mL vs. 12 microg/mL, respectively), suggesting its possible in vivo selective toxicity on cardiac tissue. This result is consistent with our previous finding that cardiovascular function is a target of the venom. In order to determine the stability of N. nomurai venom, its cytotoxicity was examined under the various temperature and pH conditions. The activity was relatively well retained at low environmental temperature (or=60 degrees C). In pH stability test, the venom has abruptly lost its activity at low pH environment (pHvenom was examined using the erythrocytes of cat, dog, human, rabbit and rat. Venom concentration-dependent hemolysis could be observed from 10 microg/mL of protein equivalents or higher with variable potencies in different species, among which dog erythrocyte was the most susceptible to the venom (EC(50)=151 microg/mL). SDS-PAGE analysis of N. nomurai venom showed the molecules of 20-40 kDa and 10-15 kDa appeared to be the major protein components of the venom.

  17. The transcriptomic and proteomic basis for the evolution of a novel venom phenotype within the Timber Rattlesnake (Crotalus horridus).

    PubMed

    Rokyta, Darin R; Wray, Kenneth P; McGivern, James J; Margres, Mark J

    2015-05-01

    The genetics underlying adaptive trait evolution describes the intersection between the probability that particular types of mutation are beneficial and the rates they arise. Snake venoms can vary in a directly meaningful manner through coding mutations and regulatory mutations. The amounts of different components determine venom efficacy, but point mutations in coding sequences can also change efficacy and function. The Timber Rattlesnake (Crotalus horridus) has populations that have evolved neurotoxic venom from the typical hemorrhagic rattlesnake venom present throughout most of its range. We identified only a handful of nonsynonymous differences in just five loci between animals with each venom type, and these differences affected lower-abundance toxins. Expression of at least 18 loci encoding hemorrhagic toxins was severely reduced in the production of neurotoxic venom. The entire phospholipase A2 toxin family was completely replaced in the neurotoxic venom, possibly through intergeneric hybridization. Venom paedomorphosis could, at best, explain only some of the loss of expression of hemorrhagic toxins. The number of potential mechanisms for altering venom composition and the patterns observed for C. horridus suggest that rapid venom evolution should occur primarily through changes in venom composition, rather than point mutations affecting coding sequences.

  18. Anti-proliferative Effects of Androctonus amoreuxi Scorpion and Cerastes cerastes Snake Venoms on Human Prostate Cancer Cells

    PubMed Central

    Akef, Hassan; Kotb, Nahla; Abo-Elmatty, Dina; Salem, Sayed

    2017-01-01

    The present study evaluated the effects of Androctonus amoreuxi scorpion venom, Cerastes cerastes snake venom and their mixture on prostate cancer cells (PC3). An MTT assay was used to determine the anti-proliferative effect of the venoms, while quantitative real time PCR was used to evaluate the expression of apoptosis-related genes (Bax and Bcl-2). Furthermore, colorimetric assays were used to measure the levels of malondialdehyde (MDA) and antioxidant enzymes. Our results show that the venoms significantly reduced PC3 cell viability in a dose-dependent manner. On the other hand, these venoms significantly decreased Bcl-2 gene expression. Additionally, C. cerastes venom significantly reduced Bax gene expression, while A. amoreuxi venom and a mixture of A. amoreuxi & C. cerastes venoms did not alter Bax expression. Consequently, these venoms significantly increased the Bax/Bcl-2 ratio and the oxidative stress biomarker MDA. Furthermore, these venoms also increased the activity levels of the antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase. Overall, the venoms have cytotoxic and anti-proliferative effects on PC3 cells. PMID:28382285

  19. Combined Peptidomic and Proteomic Analysis of Electrically Stimulated and Manually Dissected Venom from the South American Bullet Ant Paraponera clavata.

    PubMed

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

    2017-03-03

    Ants have evolved venoms rich in peptides and proteins used for predation, defense, and communication. However, they remain extremely understudied due to the minimal amount of venom secreted by each ant. The present study investigated the differences in the proteome and peptidome of the venom from the bullet ant, Paraponera clavata. Venom samples were collected from a single colony either by manual venom gland dissection or by electrical stimulation and were compared using proteomic methods. Venom proteins were separated by 2D-PAGE and identified by nanoLC-ESI-QTOF MS/MS. Venom peptides were initially separated using C18 reversed-phase high-performance liquid chromatography, then analyzed by MALDI-TOF MS. The proteomic analysis revealed numerous proteins that could be assigned a biological function (total 94), mainly as toxins, or roles in cell regulation and transport. This investigation found that ca. 73% of the proteins were common to venoms collected by the two methods. The peptidomic analysis revealed a large number of peptides (total 309) but with <20% shared by the two collection methods. There was also a marked difference between venoms obtained by venom gland dissection from different ant colonies. These findings demonstrate the rich composition and variability of P. clavata venom.

  20. Isolation and characterization of an immunosuppressive protein from venom of the pupa-specific endoparasitoid Pteromalus puparum.

    PubMed

    Wu, Ma-li; Ye, Gong-yin; Zhu, Jia-ying; Chen, Xue-xin; Hu, Cui

    2008-10-01

    In hymenopteran parasitoids devoid of symbiotic viruses, venom proteins appear to play a major role in host immune suppression and host regulation. Not much is known about the active components of venom proteins in these parasitoids, especially those that have the functions involved in the suppression of host cellular immunity. Here, we report the isolation and characterization of a venom protein Vn.11 with 24.1 kDa in size from Pteromalus puparum, a pupa-specific endoparasitoid of Pieris rapae. The Vn.11 venom protein is isolated with the combination of ammonium sulfate precipitation and anion exchange chromatography, and its purity is verified using SDS-PAGE analysis. Like crude venom, the Vn.11 venom protein significantly inhibits the spreading behavior and encapsulation ability of host hemocytes in vitro. It is suggested that this protein is an actual component of P. puparum crude venom as host cellular-immune suppressive factor.

  1. Extracts of Renealmia alpinia (Rottb.) MAAS Protect against Lethality and Systemic Hemorrhage Induced by Bothrops asper Venom: Insights from a Model with Extract Administration before Venom Injection

    PubMed Central

    Patiño, Arley Camilo; Quintana, Juan Carlos; Gutiérrez, José María; Rucavado, Alexandra; Benjumea, Dora María; Pereañez, Jaime Andrés

    2015-01-01

    Renealmia alpinia (Rottb.) MAAS, obtained by micropropagation (in vitro) and wild forms have previously been shown to inhibit some toxic activities of Bothrops asper snake venom if preincubated before injection. In this study, assays were performed in a murine model in which extracts were administered for three days before venom injection. R. alpinia extracts inhibited lethal activity of B. asper venom injected by intraperitoneal route. Median Effective Dose (ED50) values were 36.6 ± 3.2 mg/kg and 31.7 ± 5.4 mg/kg (p > 0.05) for R. alpinia wild and in vitro extracts, respectively. At a dose of 75 mg/kg, both extracts totally inhibited the lethal activity of the venom. Moreover, this dose prolonged survival time of mice receiving a lethal dose of venom by the intravenous route. At 75 mg/kg, both extracts of R. alpinia reduced the extent of venom-induced pulmonary hemorrhage by 48.0% (in vitro extract) and 34.7% (wild extract), in agreement with histological observations of lung tissue. R. alpinia extracts also inhibited hemorrhage in heart and kidneys, as evidenced by a decrease in mg of hemoglobin/g of organ. These results suggest the possibility of using R. alpinia as a prophylactic agent in snakebite, a hypothesis that needs to be further explored. PMID:25941768

  2. Epidemiology of venomous and semi-venomous snakebites (Ophidia: Viperidae, Colubridae) in the Kashan city of the Isfahan province in Central Iran

    PubMed Central

    Dehghani, Rouhullah; Mehrpour, Omid; Shahi, Morteza Panjeh; Jazayeri, Mehrdad; Karrari, Parissa; Keyler, Dan; Zamani, Nasim

    2014-01-01

    Background: Information on the epidemiology of venomous snake species responsible for envenomation to humans in Iran has not been well documented. In the Kashan city, venomous snakebite remains a recurring medical problem. Information providing the correct identification of snake species responsible for envenomation in this geographic region would be useful to regional medical clinics and personnel for the effective and optimal management of the patients. Materials and Methods: In this cross-sectional study, all patient data was collected from Kashan city and its suburbs. The specific data relating to the taxonomic identification of snakes responsible for envenomation were evaluated. A general approach to the diagnosis and management of patients was also provided. Snakes responsible for bites were transported to a laboratory, where their taxonomic classification was confirmed based on key anatomical features and morphological characteristics. Results: A total of 46 snakes were examined. Of these, 37 (80%) were non-venomous species, and 9 (20%) were identified as venomous. Seven of the nine venomous snake species (78%) were of the family Viperidae, and two specimens (22%) were in the family Colubridae. Specifically, the viperid species were Macrovipera lebetina obtusa, Pseudocerastes persicus, Pseudocerastes fieldi, and Echis carinatus. The two colubrid species were Malpolon monspessulanus insignitus and Psammophis schkari. Conclusion: Five different species of venomous snakes responsible for envenomation in the Kashan city region were confirmed. The viper, P. fieldi, was reported for the first time in the central part of Iran. PMID:24672563

  3. 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.

  4. Comparative venom gland transcriptomics of Naja kaouthia (monocled cobra) from Malaysia and Thailand: elucidating geographical venom variation and insights into sequence novelty

    PubMed Central

    Chanhome, Lawan; Tan, Nget Hong

    2017-01-01

    Background The monocled cobra (Naja kaouthia) is a medically important venomous snake in Southeast Asia. Its venom has been shown to vary geographically in relation to venom composition and neurotoxic activity, indicating vast diversity of the toxin genes within the species. To investigate the polygenic trait of the venom and its locale-specific variation, we profiled and compared the venom gland transcriptomes of N. kaouthia from Malaysia (NK-M) and Thailand (NK-T) applying next-generation sequencing (NGS) technology. Methods The transcriptomes were sequenced on the Illumina HiSeq platform, assembled and followed by transcript clustering and annotations for gene expression and function. Pairwise or multiple sequence alignments were conducted on the toxin genes expressed. Substitution rates were studied for the major toxins co-expressed in NK-M and NK-T. Results and discussion The toxin transcripts showed high redundancy (41–82% of the total mRNA expression) and comprised 23 gene families expressed in NK-M and NK-T, respectively (22 gene families were co-expressed). Among the venom genes, three-finger toxins (3FTxs) predominated in the expression, with multiple sequences noted. Comparative analysis and selection study revealed that 3FTxs are genetically conserved between the geographical specimens whilst demonstrating distinct differential expression patterns, implying gene up-regulation for selected principal toxins, or alternatively, enhanced transcript degradation or lack of transcription of certain traits. One of the striking features that elucidates the inter-geographical venom variation is the up-regulation of α-neurotoxins (constitutes ∼80.0% of toxin’s fragments per kilobase of exon model per million mapped reads (FPKM)), particularly the long-chain α-elapitoxin-Nk2a (48.3%) in NK-T but only 1.7% was noted in NK-M. Instead, short neurotoxin isoforms were up-regulated in NK-M (46.4%). Another distinct transcriptional pattern observed is the

  5. Use of stun guns for venomous bites and stings: a review.

    PubMed

    Ben Welch, E; Gales, B J

    2001-01-01

    During the past 2 decades, articles suggesting that stun guns be utilized to treat venomous bites and stings have appeared in both the lay and medical press. Although never widely considered to be standard therapy for venomous bites and stings, stun guns are still considered to be a treatment option by some medical practitioners and outdoor enthusiasts. A Medline search was performed using these terms: venomous bites, venomous stings, snake bites, spider bites, electrical, stun gun, high voltage electricity, low amperage electricity, direct current, and shock therapy. Articles selected included laboratory-based isolated venom studies, animal studies, and case reports involving humans in which a stun gun or some other source of high voltage, low amperage direct current electric shocks were used to treat actual or simulated venomous bites or stings. We concluded that the use of stun guns or other sources of high voltage, low amperage direct current electric shocks to treat venomous bites and stings is not supported by the literature.

  6. [The toxicity of venom of Bothrops (Rhinocerophris) alternatus in different areas of Cordoba State in Argentina].

    PubMed

    Rocco, Daniela M; Reati, Gustavo; Costa de Oliveira, Vanessa; Lanari, Laura C; Laskowicz, Rodrigo D; de Roodt, Adolfo R

    2013-01-01

    Snake venoms can show biochemical and toxicological variability even in specimens from the same specie. The geographical localization of the snakes is one of the factors that can influence those variations. By these reasons the venom from specimens of Bothrops (Rhinocerophis) alternatus ("crucera", "yararágrande"), one of the snakes of highest medical importance in Argentina, from three different regions of Córdoba was studied. Lehtal potency, hemorrhagic, coagulant on plasma and thrombin like activities as well as the electrophoretic patterns of venom from snakes of Calamuchita, Traslasierras and the East of the province were determined. The venom from the snakes of the three regions showed the characteristic activities of the venom of the majority of Bothrops, causing hemorrhage, hemostatic disturbances acting on plasma or directly on fibrinogen with a "thrombin like activity". The different samples were very similar regarding their biochemical characteristics and toxic potencies at difference of previous observations on venoms from the same specie in different regions of other provinces fro Argentina. Bivalent antivenom, the one used by the Provincial Ministry of Health to treat the bothropic accidents, neutralized in all the cases the toxic activities of the venom in very similar range of neutralizing potency.

  7. Direct injection of venom by a predatory wasp into cockroach brain.

    PubMed

    Haspel, Gal; Rosenberg, Lior Ann; Libersat, Frederic

    2003-09-05

    In this article, we provide direct evidence for injection of venom by a wasp into the central nervous system of its cockroach prey. Venomous predators use neurotoxins that generally act at the neuromuscular junction, resulting in different types of prey paralysis. The sting of the parasitoid wasp Ampulex compressa is unusual, as it induces grooming behavior, followed by a long-term lethargic state of its insect prey, thus ultimately providing a living meal for the newborn wasp larvae. These behavioral modifications are induced only when a sting is inflicted into the head. These unique effects of the wasp venom on prey behavior suggest that the venom targets the insect's central nervous system. The mechanism by which behavior modifying compounds in the venom transverse the blood-brain barrier to induce these central and long-lasting effects has been the subject of debate. In this article, we demonstrate that the wasp stings directly into the target ganglia in the head of its prey. To prove this assertion, we produced "hot" wasps by injecting them with (14)C radiolabeled amino acids and used a combination of liquid scintillation and light microscopy autoradiography to trace radiolabeled venom in the prey. To our knowledge, this is the first direct evidence documenting targeted delivery of venom by a predator into the brain of its prey.

  8. Characterization and biochemical analyses of venom from the ectoparasitic wasp Nasonia vitripennis (Walker) (Hymenoptera: Pteromalidae).

    PubMed

    Rivers, David B; Uckan, Fevzi; Ergin, Ekrem

    2006-01-01

    During parasitism, the ectoparasitic wasp Nasonia vitripennis (Walker) (Hymenoptera: Pteromalidae) induces a developmental arrest in host pupae that is sustained until the fly is either consumed by developing larvae or the onset of death. Bioassays using fluids collected from the female reproductive system (calyx, alkaline gland, acid gland, and venom reservoir) indicated that the venom gland and venom reservoir are the sources of the arrestant and inducer(s) of death. Infrared spectroscopic analyses revealed that crude venom is acidic and composed of amines, peptides, and proteins, which apparently are not glycosylated. Reversed phase high performance liquid chromatography (HPLC) and sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE) confirmed the proteinaceous nature of venom and that it is composed mostly of mid to high molecular weight proteins in the range of 13 to 200.5 kilodaltons (kDa). Ammonium sulfate precipitation and centrifugal size exclusion membranes were used to isolate venom proteins. SDS-PAGE protein profiles of the isolated venom fractions displaying biological activity suggest that multiple proteins contribute to arresting host development and eliciting death. Additionally, HPLC fractionation coupled with use of several internal standards implied that two of the low molecular weight proteins were apamin and histamine. However, in vitro assays using BTI-TN-5B1-4 cells contradict the presence of these agents.

  9. Tissue-Specific Venom Composition and Differential Gene Expression in Sea Anemones

    PubMed Central

    Macrander, Jason; Broe, Michael; Daly, Marymegan

    2016-01-01

    Cnidarians represent one of the few groups of venomous animals that lack a centralized venom transmission system. Instead, they are equipped with stinging capsules collectively known as nematocysts. Nematocysts vary in abundance and type across different tissues; however, the venom composition in most species remains unknown. Depending on the tissue type, the venom composition in sea anemones may be vital for predation, defense, or digestion. Using a tissue-specific RNA-seq approach, we characterize the venom assemblage in the tentacles, mesenterial filaments, and column for three species of sea anemone (Anemonia sulcata, Heteractis crispa, and Megalactis griffithsi). These taxa vary with regard to inferred venom potency, symbiont abundance, and nematocyst diversity. We show that there is significant variation in abundance of toxin-like genes across tissues and species. Although the cumulative toxin abundance for the column was consistently the lowest, contributions to the overall toxin assemblage varied considerably among tissues for different toxin types. Our gene ontology (GO) analyses also show sharp contrasts between conserved GO groups emerging from whole transcriptome analysis and tissue-specific expression among GO groups in our differential expression analysis. This study provides a framework for future characterization of tissue-specific venom and other functionally important genes in this lineage of simple bodied animals. PMID:27389690

  10. New approaches & technologies of venomics to meet the challenge of human envenoming by snakebites in India

    PubMed Central

    Warrell, David A.; Gutiérrez, José María; Calvete, Juan J.; Williams, David

    2013-01-01

    The direct estimate of 46,000 snakebite deaths in India in 2005 (1 for every 2 HIV/AIDS deaths), based on verbal autopsies, renders unrealistic the total of only 47,000 snakebite deaths in the whole world in 2010, obtained indirectly as part of the “Global Burden of Disease 2010” study. Persistent underestimation of its true morbidity and mortality has made snakebite the most neglected of all the WHO's “neglected tropical diseases”, downgrading its public health importance. Strategies to address this neglect should include the improvement of antivenom, the only specific antidote to envenoming. To accommodate increased understanding of geographical intraspecific variation in venom composition and the range of snake species that are medically important in India, the design of antivenoms (choice of venom sources and species coverage) should be reconsidered. Methods of preclinical and clinical testing should be improved. The relatively new science of venomics involves techniques and strategies for assessing the toxin composition of snake venoms directly through proteomics-centred approaches or indirectly via high-throughput venom gland transcriptomics and bioinformatic analysis. Antivenomics is translational venomics: a proteomics-based protocol to quantify the extent of cross-reactivity of antivenoms against homologous and heterologous venoms. These approaches could revolutionize the preclinical assessment of antivenom efficacy, leading to a new generation of antivenoms that are clinically more effective. PMID:24056555

  11. The relaxant effect of the Montivipera bornmuelleri snake venom on vascular contractility

    PubMed Central

    Accary, Claudine; Hraoui-Bloquet, Souad; Sadek, Riyad; Alameddine, Asma; Fajloun, Ziad; Desfontis, Jean-Claude; Mallem, Yassine

    2016-01-01

    Molecular richness of snake venoms is an important source of proteins and toxins with potent effects on the cardiovascular system. The alteration of the vascular system in the victim after a venomous snake bite is usually expressed by a significant decrease in blood pressure. Therefore, exploring snake venom to extract and characterize its biomolecules is of considerable medical interest, and formed the basis of this study. We assessed the potential of the venom of Montivipera bornmuelleri, a viper from Lebanon, to induce relaxant effect on isolated Wistar rat aorta via several mechanisms of action. The overall hypotensive effect of Montivipera bornmuelleri venom results from its synergetic action on different channels for the reduction of blood pressure. By actions of its metalloproteinases and phospholipase A2, the venom may induce the production of nitric oxide acting accordingly a vasodilator effect. It could act on the voltage-dependent potassium channels and/or the L-type calcium channels, inhibiting angiotensin converting enzyme and/or inhibiting the α1-adrenoceptors. This work demonstrates vasorelaxant effect of the Montivipera bornmuelleri venom acting on different pathways, reducing blood pressure. PMID:27826409

  12. Characterization of the venom from the spider, Araneus gemma: search for a glutamate antagonist

    SciTech Connect

    Early, S.L.

    1985-01-01

    Venom from three spiders, Argiope aurantia, Neoscona arabesca, and Araneus gemma have been shown to inhibit the binding of L-(/sup 3/H)glutamate to both GBP and synaptic membranes. The venom from Araneus gemma was shown to be the most potent of the three venoms in inhibiting the binding of L-(/sup 3/H)glutamate to GBP. Therefore, Araneus gemma venom was selected for further characterization. Venom from Araneus gemma appeared to contain two factors which inhibit the binding of L-(/sup 3/H)glutamate to GBP and at least one factor that inhibits L-glutamate-stimulated /sup 35/SCN flux. Factor I is thought to be L-glutamic acid, based on: (1) its similar mobility to glutamic acid in thin-layer chromatography and amino acid analysis, (2) the presence of fingerprint molecular ion peaks for glutamate in the mass spectrum for the methanol:water (17:1) extract and for the fraction from the HPLC-purification of the crude venom, and (3) its L-glutamate-like interaction with the sodium-dependent uptake system. Factor II appears to be a polypeptide, possibly 21 amino acids in length, and does not appear to contain any free amino groups or tryptophan. While the venom does not appear to contain any indoleamines, three catecholamines (epinephrine, epinine, dopamine) and one catecholamine metabolite (DOPAC) were detected.

  13. Comparison of total protein and enzyme levels in successive regenerations of venom from individual coralsnakes.

    PubMed

    Kopper, Randall A; Harper, George R; Occidental, Michael; Gamalie, Vlad; Spradley, Ples

    2015-07-01

    Coralsnakes produce highly potent neurotoxic venoms, but little is known about variations in specific enzyme components within a species or from one replenishment of venom to the next within the same animal. Since published studies are often conducted using venom pools from multiple snakes, individual differences are masked and variations among individual snakes and between subsequent venom regenerations from the same snake have rarely been documented. This study involves the analysis and comparison of four successive venom collections from each of nine individual coralsnakes in order to detect these differences. Significant variation was found within the successive re-synthesis of venom components. Even greater differences were observed between the venoms from similar individual snakes. Since studies of variation in enzymatic activity would be significant only if they were above these normal variations, it is important to be aware of these differences. These results suggest the importance of understanding the variations present within and between individuals of the same species when interpreting the potential significance of differences found as the result of genetic, environmental or ecological factors.

  14. Quantitation of venom antigens from European vipers in human serum or urine by ELISA.

    PubMed

    Audebert, F; Grosselet, O; Sabouraud, A; Bon, C

    1993-01-01

    We describe an enzyme-linked immunosorbent assay (ELISA) to quantitate venom antigens in human serum and urine, and thus to help evaluate the severity of envenomation due to viper bites. This assay, which is performed with commercially available polyclonal Fab'2s in a double-sandwich method, is rapid, simple, and specific for antigens of European vipers (Vipera aspis, Vipera berus, and Vipera ammodytes). No cross-reactivity was observed with other snake venoms or human serum proteins. It showed a good linear response over a wide range of concentrations of venom antigens (from 1 to 100 ng/mL). It was very sensitive, with detection limits of 7 and 2 ng/mL for Vipera aspis venom in serum and urine, respectively. This ELISA is also easily reproducible; the coefficients of variation determined at different concentrations of venom (50, 25, and 5 ng/mL) did not exceed 10% in serum and 14% in urine samples collected from different donors. This test was applied to determine the concentrations of venom in the serum of patients bitten by a viper in France and to follow its elimination as a function of time. The method is adaptable to other venoms by using other specific immunoglobulins.

  15. The in vitro toxicity of venoms from South Asian hump-nosed pit vipers (Viperidae: Hypnale).

    PubMed

    Maduwage, Kalana; Hodgson, Wayne C; Konstantakopoulos, Nicki; O'Leary, Margaret A; Gawarammana, Indika; Isbister, Geoffrey K

    2011-01-01

    Hump-nosed pit vipers (Genus Hypnale) are venomous snakes from South India and Sri Lanka. Envenoming by Hypnale species may cause significant morbidity and is characterized by local envenoming and less commonly coagulopathy and acute renal failure. Currently there are three nominal species of this genus: H. hypnale, H. zara and H. nepa. This study investigates the biochemical and pharmacological properties of the venoms from the three Hypnale species in Sri Lanka. The three Hypnale venoms had similar chromatographic profiles using reverse phase high performance liquid chromatography and fractions with procoagulant activity were identified. Hypnale venoms had potent cytotoxicity in cultured rat aorta smooth muscle cells with similar IC(50) values. The venoms had weak neurotoxic and myotoxic activity in the isolated chick biventer muscle preparation. They had mild procoagulant activity with close MCC(5) values and also phospholipase activity. Locally available polyvalent antivenom did not neutralise any venom effects. The study demonstrates that the three Hypnale venoms are similar and cytotoxicity appears to be the most potent effect, although they have mild procoagulant activity. These findings are consistent with clinical reports.

  16. Snake venomics of the Armenian mountain vipers Macrovipera lebetina obtusa and Vipera raddei.

    PubMed

    Sanz, Libia; Ayvazyan, Naira; Calvete, Juan J

    2008-07-21

    Venoms from the Armenian mountain vipers Macrovipera lebetina obtusa and Vipera raddei were analyzed by RP-HPLC, N-terminal sequencing, MALDI-TOF mass fingerprinting and CID-MS/MS. The venom proteins of M.l. obtusa and V. raddei belong to 9 and 11 families, respectively. The two mountain viper venoms share bradykinin-potentiating/C-natriuretic peptides, and proteins from the dimeric distegrin, DC-fragment, CRISP, PLA(2), serine proteinase, C-type lectin-like, L-amino acid oxidase, and Zn(2+)-dependent metalloproteinase families, albeit each species exhibits distinct relative abundances. M.l. obtusa and V. raddei venoms contain unique components, e.g. the short disintegrin obtustatin in M.l. obtusa, and Kunitz-type serine proteinase inhibitor and VEGF-like molecules in V. raddei. The toxin formulation of M.l. obtusa and V. raddei venoms may be related to their adaptation to rocky mountain ecosystems. On the other hand, the possibility that the VEGF-like proteins from V. raddei underlie the reported potential therapeutic value of V. raddei venom for regenerating damaged peripheral nerves deserves further investigations. Using a similarity coefficient, we estimate that the similarity of venom proteins between M. l. obtusa and M. l. transmediterranea is less than 4%. Although this result would support the classification of M.l. obtusa and M.l. transmediterranea as different species, additional detailed genomic analyses are also required.

  17. A comparative study of the biological properties of venoms of some old world vipers (subfamily viperinae).

    PubMed

    Tan, N H; Ponnudurai, G

    1992-02-01

    1. The hemorrhagic, procoagulant, anticoagulant, phosphodiesterase, hyaluronidase, alkaline phosphomonoesterase, 5'-nucleotidase, arginine ester hydrolase, phospholipase A, L-amino acid oxidase and protease activities of 30 samples of venoms from nine species (12 taxa) of the old world vipers (Subfamily Viperinae) including snakes from the genera Bitis, Causus, Cerastes, Echis, Eristicophis and Pseudocerastes, were determined and the Sephadex G-75 gel filtration patterns for some of the venoms were also examined. 2. Examination of the biological properties of the venoms of the Viperinae tested indicates the presence of common venom biological characteristics at the various phylogenic levels. 3. Venoms of most species of the Viperinae examined exhibited characteristic biological properties at the species level, and this allows the differentiation of the Viperinae species by differences in their biological properties. 4. Particularly useful for this purpose, are the effects of venom on kaolin-cephalin clotting time of platelet poor rabbit plasma and the Sephadex G-75 gel filtration pattern and arginine ester hydrolase activity of the venom.

  18. Pelagia noctiluca (Scyphozoa) Crude Venom Injection Elicits Oxidative Stress and Inflammatory Response in Rats

    PubMed Central

    Bruschetta, Giuseppe; Impellizzeri, Daniela; Morabito, Rossana; Marino, Angela; Ahmad, Akbar; Spanò, Nunziacarla; La Spada, Giuseppa; Cuzzocrea, Salvatore; Esposito, Emanuela

    2014-01-01

    Cnidarian toxins represent a rich source of biologically active compounds. Since they may act via oxidative stress events, the aim of the present study was to verify whether crude venom, extracted from the jellyfish Pelagia noctiluca, elicits inflammation and oxidative stress processes, known to be mediated by Reactive Oxygen Species (ROS) production, in rats. In a first set of experiments, the animals were injected with crude venom (at three different doses 6, 30 and 60 µg/kg, suspended in saline solution, i.v.) to test the mortality and possible blood pressure changes. In a second set of experiments, to confirm that Pelagia noctiluca crude venom enhances ROS formation and may contribute to the pathophysiology of inflammation, crude venom-injected animals (30 µg/kg) were also treated with tempol, a powerful antioxidant (100 mg/kg i.p., 30 and 60 min after crude venom). Administration of tempol after crude venom challenge, caused a significant reduction of each parameter related to inflammation. The potential effect of Pelagia noctiluca crude venom in the systemic inflammation process has been here demonstrated, adding novel information about its biological activity. PMID:24727391

  19. The transcriptome recipe for the venom cocktail of Tityus bahiensis scorpion.

    PubMed

    de Oliveira, Ursula Castro; Candido, Denise Maria; Dorce, Valquíria Abrão Coronado; Junqueira-de-Azevedo, Inácio de Loiola Meirelles

    2015-03-01

    Scorpion venom is a mixture of peptides, including antimicrobial, bradykinin-potentiating and anionic peptides and small to medium proteins, such as ion channel toxins, metalloproteinases and phospholipases that together cause severe clinical manifestation. Tityus bahiensis is the second most medically important scorpion species in Brazil and it is widely distributed in the country with the exception of the North Region. Here we sequenced and analyzed the transcripts from the venom glands of T. bahiensis, aiming at identifying and annotating venom gland expressed genes. A total of 116,027 long reads were generated by pyrosequencing and assembled in 2891 isotigs. An annotation process identified transcripts by similarity to known toxins, revealing that putative venom components represent 7.4% of gene expression. The major toxins identified are potassium and sodium channel toxins, whereas metalloproteinases showed an unexpected high abundance. Phylogenetic analysis of deduced metalloproteinases from T. bahiensis and other scorpions revealed a pattern of ancient and intraspecific gene expansions. Other venom molecules identified include antimicrobial, anionic and bradykinin-potentiating peptides, besides several putative new venom components. This report provides the first attempt to massively identify the venom components of this species and constitutes one of the few transcriptomic efforts on the genus Tityus.

  20. Hemolytic activity of venom from crown-of-thorns starfish Acanthaster planci spines

    PubMed Central

    2013-01-01

    Background The crown-of-thorns starfish Acanthaster planci is a venomous species from Taiwan whose venom provokes strong hemolytic activity. To understand the hemolytic properties of A. planci venom, samples were collected from A. planci spines in the Penghu Islands, dialyzed with distilled water, and lyophilized into A. planci spine venom (ASV) powder. Results Both crude venom and ASV cause 50% hemolysis at a concentration of 20 μg/mL. The highest hemolytic activity of ASV was measured at pH 7.0-7.4; ASV-dependent hemolysis was sharply reduced when the pH was lower than 3 or greater than 8. There was almost no hemolytic activity when the Cu2+ concentration was increased to 10 mM. Furthermore, incubation at 100°C for 30 to 60 minutes sharply decreased the hemolytic activity of ASV. After treatment with the protease α-chymotrypsin, the glycoside hydrolase cellulase, and the membrane component cholesterin, the hemolytic activity of ASV was significantly inhibited. Conclusions The results of this study provide fundamental information about A. planci spine venom. The hemolytic activity was affected by pH, temperature, metal ions, EDTA, cholesterin, proteases, and glycoside hydrolases. ASV hemolysis was inhibited by Cu2+, cholesterin, α-chymotrypsin, and cellulose, factors that might prevent the hemolytic activity of venom and provide the medical treatment for sting. PMID:24063308

  1. A survey of the venom of the spider Lycosa vittata by biochemical, pharmacological and transcriptomic analyses.

    PubMed

    Zhang, Fan; Liu, Changjun; Tan, Huaxin; Wang, Hengyun; Jiang, Yinjie; Liang, Songping; Zhang, Fuping; Liu, Zhonghua

    2015-12-01

    Lycosa vittata, mainly distributed in the southwest of China, is a medium-sized and venomous spider, whose venom remains unexplored so far. This study aims to present an overview of the venom. It mainly consisted of diverse peptides and exhibited inhibitory effects on voltage-gated ion channels in rat dorsal root ganglia neurons, with a strongest inhibition on tetrodotoxin-sensitive and tetrodotoxin-resistant voltage-gated Na(+) channels. Interestingly, it exerted cytotoxicity to cancer cells, with approximately 10-fold selectivity on PC-3 over others, implying the existence of selective anti-PC-3 agents in the venom. Moreover, 51 toxin-like peptides were deduced from the venom gland transcriptome. Bioinformatic analyses suggested their structures might have some distinguished properties and their predicted functions were consistent with the venom activities. This study suggests that the venom is an attractive source of neurotoxins with therapeutic significance, and provides references for the structure and function investigation of specific toxins in the future.

  2. Effect of heparin and antivenom on skeletal muscle damage produced by Bothrops jararacussu venom.

    PubMed

    Calil-Elias, S; Martinez, A M B; Melo, P A

    2002-04-01

    We examined the effect of treatment with heparin and polyvalent antivenom on mice muscle Extensor digitorum longus (EDL) regeneration, after damage induced by injection of Bothrops jararacussu crude venom over the muscle of the right posterior limb. The mice were separated into groups and each group received treatment, by intravenous route with either high molecular weight heparin (H), low molecular weight heparin (LMWH), polyvalent antivenom (PAV) or with the combination of PAV plus H or PAV plus LMWH at 15 minutes and 4 hours after the injection of the venom. Myotoxicity was measured by the increase in plasma creatine kinase (CK) activity at two hours after the injection of the venom. The histological changes in EDL at 1, 3, 7 and 21 days after the injection of the venom were analyzed by light microscopy. In each group the normal and regenerated muscle fibers were quantified using Scion Image computer program. We also evaluated in vitro, the influence of these substances in the proteolytic and phospholipase activities of the venom. Heparins decreased the proteolytic activity of the venom but did not affect its phospholipase activity. However the PAV antagonized both activities. PAV and its combinations showed antimyotoxic activity, according to the magnitude of CK plasma levels. At 21 days the regeneration was observed in all animals, also in those that received only the venom. All treatments, except LMWH, promote a significant increase in the number of muscle fibers.

  3. A rapidly diverging superfamily of peptide toxins in venomous Gemmula species.

    PubMed

    Heralde, Francisco M; Imperial, Julita; Bandyopadhyay, Pradip K; Olivera, Baldomero M; Concepcion, Gisela P; Santos, Ameurfina D

    2008-04-01

    The gem turrids (genus Gemmula Weinkauff, 1875) are venomous snails in the family Turridae. A gene superfamily of disulfide-rich peptides expressed in Gemmula venom ducts was characterized. Gemmula speciosa (Reeve, 1843) venom duct cDNA clones revealed two different conotoxin-like prepropeptide precursors, with identical signal sequences, a largely conserved pro region, and a cysteine-rich C-terminal mature peptide region. The conserved signal sequence was used to successfully amplify homologous genes from three other Gemmula species; all had the same pattern of Cys residues in the predicted mature venom peptide. Although the signal sequence and propeptide regions were highly conserved, the mature toxin regions diverged greatly in sequence, except that the Cys residues were conserved. We designate this as the Pg-gene superfamily (Pg-superfamily) of Gemmula venom peptides. Purification of two members of the family directly from G. speciosa venom was achieved; amino acid sequence analysis revealed that these peptides are highly posttranslationally modified. With at least 10-fold as many species of turrids as cone snails, identification of rapidly diversifying gene superfamilies such as the Pg-superfamily of Gemmula is essential before the facile and systematic discovery and characterization of peptide toxins from turrid venoms can be achieved.

  4. 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.

  5. Peripheral and central effects of intracerebroventricular microinjection of Hottentotta gentili (Pallary, 1924) (Scorpiones, Buthidae) venom.

    PubMed

    El Hidan, Moulay Abdelmonaim; Touloun, Oulaid; El Hiba, Omar; Laadraoui, Jawad; Ferehan, Hind; Boumezzough, Ali

    2016-03-01

    Central effects of scorpion venom toxins have been neglected, due both to the common belief that scorpion venoms act by targeting peripheral organs and also to the misunderstanding that these peptides do not cross the brain-blood barrier (BBB). Determining whether scorpion neurotoxicity is restricted to peripheral actions or whether a central mechanism may be partly responsible for systemic manifestations could be crucial in clinical therapy trends. The present study therefore aims to assess histopathological damages in some organs (heart, kidney, liver, and lungs) and the related biochemical impairments, together with a neurobehavioral investigation following an intracerebroventricular (i.c.v) micro-injection of Hottentotta gentili (Scorpiones, Buthidae) venom (0.47 μg/kg). I.c.v. injection of venom produced focal fragmentation of myocardial fibers, while lungs showed rupture of the alveolar structure. Concurrently, there was a significant rise in the serum enzymes levels of ASAT, ALAT, CPK and LDH. Meanwhile, we observed behavioral alterations such as a hypoactivity, and in addition the venom seems to have a marked anxiogenic-like effect. The present investigation has brought new experimental evidence of a peripheral impact of central administration of H. gentili venom, such impact was manifested by physiological and behavioral disturbances, the last of these appearing to reflect profound neuro-modulatory action of H. gentili venom.

  6. In vitro diagnosis of Hymenoptera venom allergy and further development of component resolved diagnostics.

    PubMed

    Ebo, Didier G; Van Vaerenbergh, Matthias; de Graaf, Dirk C; Bridts, Chris H; De Clerck, Luc S; Sabato, Vito

    2014-03-01

    For most people Hymenoptera stings result in transient and bothersome local inflammatory responses characterized by pain, itching, redness and swelling. In contrast, for those presenting an IgE-mediated allergic reaction, a re-sting may cause life-threatening reactions. In such patients, correct diagnosis is an absolute prerequisite for effective management, i.e. venom-specific immunotherapy. Generally, identification of the offending insect involves a detailed history along with quantification of venom-specific IgE antibodies and venom skin tests. Unfortunately, due to uncertainties associated with both tests, correct diagnosis is not always straightforward. This review summarizes the potentials and limitations of the various in vitro tests that are currently being used in the diagnosis of Hymenoptera venom allergy. Particular attention is paid to the potential of novel cellular tests such as basophil activation tests and component-resolved diagnosis with recombinant venom allergens in the diagnostic approach of patients with difficult diagnosis, i.e. cases in whom traditional venom specific IgE and skin tests yield equivocal or negative results. Finally, this review also covers the recent discoveries in the field of proteome research of Hymenoptera venoms and the selection of cell types for recombinant allergens production.

  7. The Trail Pheromone of the Venomous Samsum Ant, Pachycondyla sennaarensis

    PubMed Central

    Mashaly, Ashraf Mohamed Ali; Ahmed, Ashraf Mohamed; Al—Abdullah, Mosa Abdullah; Al—Khalifa, Mohamed Saleh

    2011-01-01

    Ant species use branching networks of pheromone trails for orientation between nest and resources. The current study demonstrated that workers of the venomous samsum ant, Pachycondyla sennaarensis (Mayr) (Hymenoptera: Formicidae: Ponerinae), employ recruitment trail pheromones discharged from the Dufour's gland. Secretions of other abdomen complex glands, as well as hindgut gland secretions, did not evoke trail following. The optimum concentration of trail pheromone was found to be 0.1 gland equivalent/40 cm trail. This concentration demonstrated effective longevity for about one hour. This study also showed that P. sennaarensis and Tapinoma simrothi each respond to the trail pheromones of the other species as well as their own. PMID:21529253

  8. Therapeutic potential of cone snail venom peptides (conopeptides).

    PubMed

    Vetter, Irina; Lewis, Richard J

    2012-01-01

    Cone snails have evolved many 1000s of small, structurally stable venom peptides (conopeptides) for prey capture and defense. Whilst < 0.1% have been pharmacologically characterised, those with known function typically target membrane proteins of therapeutic importance, including ion channels, transporters and GPCRs. Several conopeptides reduce pain in animals models, with one in clinical development (χ-conopeptide analogue Xen2174) and one marketed (ω- conotoxin MVIIA or Prialt) for the treatment of severe pain. In addition to their therapeutic potential, conopeptides have been valuable probes for studying the role of a number of key membrane proteins in normal and disease physiology.

  9. [Venomous and poisonous animals. III. Elapidae snake envenomation].

    PubMed

    Chippaux, J P

    2007-02-01

    Envenomation by Elapidae snakes is less frequent than by Viperidae snakes but represents a true medical emergency due to rapid progression of cobra syndrome. Elapidae venom contains neurotoxins that paralyze striated muscles especially in the thoracic cavity. Respiratory paralysis can occur within a few hours and is preceded by neurological symptoms (local paresthesia and paresis progressing to the cranial nerves). When cobra envenomation is suspected, antivenom administration by the direct venous route must be undertaken as quickly as possible to stop the envenomation process. Artificial ventilation is necessary in case of dyspnea.

  10. 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