Venomics, Venom Proteomics and Venom Transcriptomics

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: closed (31 December 2015) | Viewed by 92405

Special Issue Editor


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Guest Editor
School of Biological Sciences, 501 20th. St., CB 92, University of Northern Colorado, Greeley, CO 80639-0017 USA
Interests: reptile venom proteomics and evolution; toxin evolution and structure/function relationships; venom proteinases; biochemical ecology of venomous reptiles

Special Issue Information

Dear Colleagues,

Omics technologies have revolutionized many areas of research in biology, and toxinology is no exception. Over the last ten years, there has been a tremendous increase in the use of proteomic and transcriptomic methods to provide a greater understanding of animal venoms and toxins, their complexity and their evolution. This Special Issue of Toxins will bring together reviews authored by some of the leaders in the use of –omics technologies in toxinology, with the intent of providing an up to date review of advancements in this field and identifying trends and directions for future research endeavors. As more tissues are subjected to transcriptomic analyses, our assumptions of what constitutes a venom or a toxin are being significantly questioned, and with increased sensitivity of detection, deciding which components are actually “true venom” constituents becomes difficult to determine unequivocally. Further, as –omics technologies multiply, mature, and diversify, there is a growing need to create high-throughput functional assays to evaluate the myriad of compounds being catalogued. This Special Issue, therefore, seeks not only to provide reviews but also to identify areas where new tools, methods and approaches will allow researchers to extract as much information as possible out of the tremendous data sets currently being generated. Join us as an author—contributions are being solicited, with a deadline of 31 December 2015.

Prof. Dr. Stephen P. Mackessy
Guest Editor

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Keywords

  • evolution
  • genomics
  • neofunctionalization
  • next-gen sequencing
  • peptide
  • protein
  • structure/function
  • transcriptome
  • toxin
  • venom

Published Papers (11 papers)

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Research

Jump to: Review

945 KiB  
Article
Proteomic Characterization and Comparison of Malaysian Tropidolaemus wagleri and Cryptelytrops purpureomaculatus Venom Using Shotgun-Proteomics
by Syafiq Asnawi Zainal Abidin, Pathmanathan Rajadurai, Md Ezharul Hoque Chowdhury, Muhamad Rusdi Ahmad Rusmili, Iekhsan Othman and Rakesh Naidu
Toxins 2016, 8(10), 299; https://doi.org/10.3390/toxins8100299 - 18 Oct 2016
Cited by 23 | Viewed by 7313
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Venomics, Venom Proteomics and Venom Transcriptomics)
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4470 KiB  
Article
Interaction between TNF and BmooMP-Alpha-I, a Zinc Metalloprotease Derived from Bothrops moojeni Snake Venom, Promotes Direct Proteolysis of This Cytokine: Molecular Modeling and Docking at a Glance
by Maraisa Cristina Silva, Tamires Lopes Silva, Murilo Vieira Silva, Caroline Martins Mota, Fernanda Maria Santiago, Kelly Cortes Fonseca, Fábio Oliveira, Tiago Wilson Patriarca Mineo and José Roberto Mineo
Toxins 2016, 8(7), 223; https://doi.org/10.3390/toxins8070223 - 20 Jul 2016
Cited by 7 | Viewed by 5855
Abstract
Tumor necrosis factor (TNF) is a major cytokine in inflammatory processes and its deregulation plays a pivotal role in several diseases. Here, we report that a zinc metalloprotease extracted from Bothrops moojeni venom (BmooMP-alpha-I) inhibits TNF directly by promoting its degradation. This inhibition [...] Read more.
Tumor necrosis factor (TNF) is a major cytokine in inflammatory processes and its deregulation plays a pivotal role in several diseases. Here, we report that a zinc metalloprotease extracted from Bothrops moojeni venom (BmooMP-alpha-I) inhibits TNF directly by promoting its degradation. This inhibition was demonstrated by both in vitro and in vivo assays, using known TLR ligands. These findings are supported by molecular docking results, which reveal interaction between BmooMP-alpha-I and TNF. The major cluster of interaction between BmooMP-alpha-I and TNF was confirmed by the structural alignment presenting Ligand Root Mean Square Deviation LRMS = 1.05 Å and Interactive Root Mean Square Deviation IRMS = 1.01 Å, this result being compatible with an accurate complex. Additionally, we demonstrated that the effect of this metalloprotease on TNF is independent of cell cytotoxicity and it does not affect other TLR-triggered cytokines, such as IL-12. Together, these results indicate that this zinc metalloprotease is a potential tool to be further investigated for the treatment of inflammatory disorders involving TNF deregulation. Full article
(This article belongs to the Special Issue Venomics, Venom Proteomics and Venom Transcriptomics)
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Article
Venomic Analysis of the Poorly Studied Desert Coral Snake, Micrurus tschudii tschudii, Supports the 3FTx/PLA2 Dichotomy across Micrurus Venoms
by Libia Sanz, Davinia Pla, Alicia Pérez, Yania Rodríguez, Alfonso Zavaleta, Maria Salas, Bruno Lomonte and Juan J. Calvete
Toxins 2016, 8(6), 178; https://doi.org/10.3390/toxins8060178 - 7 Jun 2016
Cited by 42 | Viewed by 6791
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Venomics, Venom Proteomics and Venom Transcriptomics)
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Article
Venom of the Coral Snake Micrurus clarki: Proteomic Profile, Toxicity, Immunological Cross-Neutralization, and Characterization of a Three-Finger Toxin
by Bruno Lomonte, Mahmood Sasa, Paola Rey-Suárez, Wendy Bryan and José María Gutiérrez
Toxins 2016, 8(5), 138; https://doi.org/10.3390/toxins8050138 - 5 May 2016
Cited by 37 | Viewed by 8646
Abstract
Micrurus clarki is an uncommon coral snake distributed from the Southeastern Pacific of Costa Rica to Western Colombia, for which no information on its venom could be found in the literature. Using a ‘venomics’ approach, proteins of at least nine families were identified, [...] Read more.
Micrurus clarki is an uncommon coral snake distributed from the Southeastern Pacific of Costa Rica to Western Colombia, for which no information on its venom could be found in the literature. Using a ‘venomics’ approach, proteins of at least nine families were identified, with a moderate predominance of three-finger toxins (3FTx; 48.2%) over phospholipase A2 (PLA2; 36.5%). Comparison of this venom profile with those of other Micrurus species suggests that it may represent a more balanced, ‘intermediate’ type within the dichotomy between 3FTx- and PLA2-predominant venoms. M. clarki venom was strongly cross-recognized and, accordingly, efficiently neutralized by an equine therapeutic antivenom against M. nigrocinctus, revealing their high antigenic similarity. Lethal activity for mice could be reproduced by a PLA2 venom fraction, but, unexpectedly, not by fractions corresponding to 3FTxs. The most abundant venom component, hereby named clarkitoxin-I, was identified as a short-chain (type I) 3FTx, devoid of lethal effect in mice, whose target remains to be defined. Its amino acid sequence of 66 residues shows high similarity with predicted sequences of venom gland transcripts described for M. fulvius, M. browni, and M. diastema. Full article
(This article belongs to the Special Issue Venomics, Venom Proteomics and Venom Transcriptomics)
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Article
Quantitative Proteomic Analysis of Venoms from Russian Vipers of Pelias Group: Phospholipases A2 are the Main Venom Components
by Sergey I. Kovalchuk, Rustam H. Ziganshin, Vladislav G. Starkov, Victor I. Tsetlin and Yuri N. Utkin
Toxins 2016, 8(4), 105; https://doi.org/10.3390/toxins8040105 - 12 Apr 2016
Cited by 29 | Viewed by 5794
Abstract
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. [...] Read more.
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. Full article
(This article belongs to the Special Issue Venomics, Venom Proteomics and Venom Transcriptomics)
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Article
Tentacle Transcriptome and Venom Proteome of the Pacific Sea Nettle, Chrysaora fuscescens (Cnidaria: Scyphozoa)
by Dalia Ponce, Diane L. Brinkman, Jeremy Potriquet and Jason Mulvenna
Toxins 2016, 8(4), 102; https://doi.org/10.3390/toxins8040102 - 5 Apr 2016
Cited by 73 | Viewed by 12666
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Venomics, Venom Proteomics and Venom Transcriptomics)
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1964 KiB  
Article
Characterization and Recombinant Expression of Terebrid Venom Peptide from Terebra guttata
by John Moon, Juliette Gorson, Mary Elizabeth Wright, Laurel Yee, Samer Khawaja, Hye Young Shin, Yasmine Karma, Rajeeva Lochan Musunri, Michelle Yun and Mande Holford
Toxins 2016, 8(3), 63; https://doi.org/10.3390/toxins8030063 - 3 Mar 2016
Cited by 7 | Viewed by 7098
Abstract
Venom peptides found in terebrid snails expand the toolbox of active compounds that can be applied to investigate cellular physiology and can be further developed as future therapeutics. However, unlike other predatory organisms, such as snakes, terebrids produce very small quantities of venom, [...] Read more.
Venom peptides found in terebrid snails expand the toolbox of active compounds that can be applied to investigate cellular physiology and can be further developed as future therapeutics. However, unlike other predatory organisms, such as snakes, terebrids produce very small quantities of venom, making it difficult to obtain sufficient amounts for biochemical characterization. Here, we describe the first recombinant expression and characterization of terebrid peptide, teretoxin Tgu6.1, from Terebra guttata. Tgu6.1 is a novel forty-four amino acid teretoxin peptide with a VI/VII cysteine framework (C–C–CC–C–C) similar to O, M and I conotoxin superfamilies. A ligation-independent cloning strategy with an ompT protease deficient strain of E. coli was employed to recombinantly produce Tgu6.1. Thioredoxin was introduced in the plasmid to combat disulfide folding and solubility issues. Specifically Histidine-6 tag and Ni-NTA affinity chromatography were applied as a purification method, and enterokinase was used as a specific cleavage protease to effectively produce high yields of folded Tgu6.1 without extra residues to the primary sequence. The recombinantly-expressed Tgu6.1 peptide was bioactive, displaying a paralytic effect when injected into a Nereis virens polychaete bioassay. The recombinant strategy described to express Tgu6.1 can be applied to produce high yields of other disulfide-rich peptides. Full article
(This article belongs to the Special Issue Venomics, Venom Proteomics and Venom Transcriptomics)
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Article
Snake Venomics and Antivenomics of Bothrops diporus, a Medically Important Pitviper in Northeastern Argentina
by Carolina Gay, Libia Sanz, Juan J. Calvete and Davinia Pla
Toxins 2016, 8(1), 9; https://doi.org/10.3390/toxins8010009 - 25 Dec 2015
Cited by 23 | Viewed by 6943
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Venomics, Venom Proteomics and Venom Transcriptomics)
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2195 KiB  
Article
Phylloseptin-PBa—A Novel Broad-Spectrum Antimicrobial Peptide from the Skin Secretion of the Peruvian Purple-Sided Leaf Frog (Phyllomedusa Baltea) Which Exhibits Cancer Cell Cytotoxicity
by Yuantai Wan, Chengbang Ma, Mei Zhou, Xinping Xi, Lei Li, Di Wu, Lei Wang, Chen Lin, Juan Chavez Lopez, Tianbao Chen and Chris Shaw
Toxins 2015, 7(12), 5182-5193; https://doi.org/10.3390/toxins7124878 - 1 Dec 2015
Cited by 22 | Viewed by 7700
Abstract
Antimicrobial peptides from amphibian skin secretion display remarkable broad-spectrum antimicrobial activity and are thus promising for the discovery of new antibiotics. In this study, we report a novel peptide belonging to the phylloseptin family of antimicrobial peptides, from the skin secretion of the [...] Read more.
Antimicrobial peptides from amphibian skin secretion display remarkable broad-spectrum antimicrobial activity and are thus promising for the discovery of new antibiotics. In this study, we report a novel peptide belonging to the phylloseptin family of antimicrobial peptides, from the skin secretion of the purple-sided leaf frog, Phyllomedusa baltea, which was named Phylloseptin-PBa. Degenerate primers complementary to putative signal peptide sites of frog skin peptide precursor-encoding cDNAs were designed to interrogate a skin secretion-derived cDNA library from this frog. Subsequently, the peptide was isolated and identified using reverse phase HPLC and MS/MS fragmentation. The synthetic replicate was demonstrated to have activity against S. aureus, E. coli and C. albicans at concentrations of 8, 128 and 8 mg/L, respectively. In addition, it exhibited anti-proliferative activity against the human cancer cell lines, H460, PC3 and U251MG, but was less active against a normal human cell line (HMEC). Furthermore, a haemolysis assay was performed to assess mammalian cell cytotoxicity of Phylloseptin-PBa. This peptide contained a large proportion of α-helical domain, which may explain its antimicrobial and anticancer activities. Full article
(This article belongs to the Special Issue Venomics, Venom Proteomics and Venom Transcriptomics)
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Review

Jump to: Research

4056 KiB  
Review
Colubrid Venom Composition: An -Omics Perspective
by Inácio L. M. Junqueira-de-Azevedo, Pollyanna F. Campos, Ana T. C. Ching and Stephen P. Mackessy
Toxins 2016, 8(8), 230; https://doi.org/10.3390/toxins8080230 - 23 Jul 2016
Cited by 67 | Viewed by 10538
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Venomics, Venom Proteomics and Venom Transcriptomics)
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3723 KiB  
Review
From Mollusks to Medicine: A Venomics Approach for the Discovery and Characterization of Therapeutics from Terebridae Peptide Toxins
by Aida Verdes, Prachi Anand, Juliette Gorson, Stephen Jannetti, Patrick Kelly, Abba Leffler, Danny Simpson, Girish Ramrattan and Mandë Holford
Toxins 2016, 8(4), 117; https://doi.org/10.3390/toxins8040117 - 19 Apr 2016
Cited by 39 | Viewed by 11391
Abstract
Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this [...] Read more.
Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1) delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2) identification and classification of putative teretoxins through omics methodologies, including genomics, transcriptomics, and proteomics; (3) chemical and recombinant synthesis of promising peptide toxins; (4) structural characterization through experimental and computational methods; (5) determination of teretoxin bioactivity and molecular function through biological assays and computational modeling; (6) optimization of peptide toxin affinity and selectivity to molecular target; and (7) development of strategies for effective delivery of venom peptide therapeutics. While our research focuses on terebrids, the venomics approach outlined here can be applied to the discovery and characterization of peptide toxins from any venomous taxa. Full article
(This article belongs to the Special Issue Venomics, Venom Proteomics and Venom Transcriptomics)
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