1995; Bayrhuber et al. 2007; Kuhn-Nentwig et al. 2016). One species, the bearded fireworm, is especially fond of corals. 2013; Fernández et al. The putative toxins identified in this study are predominantly involved in three major biological activities: hemostasis, inflammatory response, and allergic reactions, all processes that are commonly disrupted after fireworm envenomations (Smith 2002; Ottuso 2013; Haddad 2015) (fig. 4). Leeches use several anticoagulants and antihemostatic toxins to prevent coagulation in the host tissue during blood feeding (Kvist et al. von Reumont BM, Undheim EAB, Jauss RT, Jenner RA. Dracunculiasis, also called Guinea-worm disease (GWD), is a parasitic infection by the Guinea worm. 2013). Venoms tend to be complex proteinaceous mixtures of larger compounds that must be injected into the prey, whereas poisons are usually composed of small chemical compounds such as alkaloids that can be readily absorbed (Daly 1995; Casewell et al. Cystatins have been found in the venoms of several organisms, such as reptiles, caterpillars, ticks, mosquitoes, nematodes, and segmented worms (Hartmann and Lucius 2003; Fry et al. 2009; Casewell et al. ... fireworm sting, bristleworm, bristle worm. 2014b) (fig. 7). Turripeptides are short peptides with conserved cysteine patterns, discovered from the venom of turrids, a diverse group of conoidean mollusks related to cone snails and terebrids (Watkins et al. Thieffry M, Bon C, Manaranche R, Saliou B, Israël M. Vaiyapuri S, Wagstaff SC, Harrison RA, Gibbins JM, Hutchinson EG. Tree reconstructed with RAxML-HPC-PTTHREADS v8.2.10 and support values estimated through a rapid bootstrap algorithm and 1,000 pseudoreplicates. 2016). Thus, guaranteeing the best BLAST hit for all our toxin candidates is a known venom protein. Once the rubber cement has dried, peel it off to remove or to pull the residual spines out of the skin. Transcriptomes of P. jeffreysii and E. complanata were generated as described in Weigert et al. Wiklund H, Nygren A, Pleijel F, Sundberg P. Oxford University Press is a department of the University of Oxford. Barroso R, Klautau M, Solé-Cava AM, Paiva PC. For convenience, we classified them into four functional categories: protease inhibitors (cystatin, lipocalin, serpin, and kazal-type and kunitz-type protease inhibitors), proteolytic enzymes (metalloproteinase M12, peptidase S1, and peptidase S10), neurotoxins (ShK-like, spider toxins, and turripeptide-like), and other proteins (CAP, C-type lectins, and phospholipases). 2005; Takác et al. S2, Supplementary Material online). 2010; Borda et al. Representatives of species that use venom for predation are also shown, highlighted in blue: bloodworm Glycera capitata (E) and leech Helobdella europaea (F). These symptoms are consistent with the expression of the putative peptide toxins and venom proteins identified in this study. 2011). S10 peptidases are also recognized allergens of bee venom, inducing strong systemic IgE-mediated allergic reactions (Li et al. 2008) for cross validation. However, conflicting evidence regarding the function of chaetae as a venom delivery apparatus and the inability to identify glandular tissue near the base of the chaetae has generated some doubts (Eckert 1985; Schulze et al. Interestingly, one Paramphinome transcript (PJKAZ1) clusters with Vasotab, a kazal-type inhibitor identified from the salivary glands of the horse fly Hybomitra bimaculata that functions as a vasodilator (Takác et al. We recovered one orthologous cluster that includes 9 ctenitoxin-like sequences. We have identified one orthologous cluster of ShKT-domain toxins including 5 transcripts among the fireworm toxin-like genes. Bon C, Saliou B, Thieffry M, Manaranche R. Borda E, Kudenov JD, Bienhold C, Rouse GW. The putative species-specific toxins identified include most notably homologs of sea anemone and conoidean mollusk neurotoxins and several cytolysins (fig. 3). 2012, 2015; Ahrens et al. Despite this difficulty, we provide several lines of evidence that strongly suggest the sequences we identified here are likely coding for putative toxins. Vinegar, ammonia, meat tenderizer, or heat can inactivate the toxin in jellyfish venom. 2000; Law et al. See supplementary table S1, Supplementary Material online, for assembly statistics. 2014, 2016; von Reumont et al. Pain may persist for days rather than hours. 2014) and trimmed reads were re-evaluated with FastQC to ensure the high quality of the data after the trimming process. S5, Supplementary Material online). 2011) against hidden Markov models (HMM) profiles built from alignments of 24 known venom protein classes derived from a recent study of bloodworm (Glyceridae) venom gland transcriptomics (von Reumont et al. 2005; Isaeva et al. Harian Metro reported that Mohd Fadzil Mohd Yunus who is from Kampung Durian Hijau, Terachi was stung by a golden fireworm […] The total 868 toxin-like genes recovered from the transcriptomes of the three species (438 from E. complanata, 261 from H. carunculata and 169 from P. jeffreysii) (fig. 3) were compared and 34 clusters of orthologous genes (supplementary table S3, Supplementary Material online) that represent 13 distinct toxin classes were identified (fig. 4). For full access to this pdf, sign in to an existing account, or purchase an annual subscription. 2017). Although rare, there are also reports of systemic reactions including nausea, cardiac, and respiratory anaphylactic reactions (Ottuso 2013). 2009; Undheim et al. More recently, in their ultrastructural study of Eurythoe complanata, Tilic et al. Transcriptomic analyses of fireworms, H. carunculata, E. complanata, and P. jeffreysii, revealed a wide diversity of putative toxin genes belonging to toxin classes that have been convergently recruited into other animal venoms (fig. 3 and supplementary files S2–S4, Supplementary Material online). 2014b, 2017; Huang et al. Initially there are no symptoms. 2016). 2012). —Venomics pipeline for the identification of toxin homologs. S1, Supplementary Material online). 2008; Ding et al. Other, groups a variety of less diverse toxin homologs (see supplementary files S2–S4, Supplementary Material online). I bought a Hectors goby. http://en.wikipedia.org/wiki/Bearded_fireworm, http://www.drcharleshecht.com/contact-us/. After this second comparison, we filter out the toxin-like transcripts that are more similar to other genes with nonvenom-related functions. 2013; Sigle and Ramalho-Ortigão 2013; Negulescu et al. First, It has been shown that gene models predicted to encode toxin-like proteins by similarity searches matched known venom components more likely if they are overexpressed in the venom gland and if their best BLAST hit is a known venom protein (as opposed to another protein from the UniProtKB database) (Rodríguez De La Vega and Giraud 2016). 2013). The symptoms can last several days or even weeks and the recommended treatment includes applying vinegar and hot water to the affected area (Smith 2002; Schulze et al. The bristle worm is also known as the fireworm. Interestingly, the Eurythoe and Paramphinome putative cystatins do not cluster with other cystatin homologs from nonvenomous annelids (Capitella and Perinereis) suggesting the involvement of this protein in fireworm toxicity. 2015; Weigert and Bleidorn 2016). 2016; Cipriani et al. This first of two articles will review the well-known jellyfish stings and other less familiar venomous organisms such as the bristle worm and the sting ray. 2013; von Reumont et al. Polychaeta, Myzostomida, Pogonophora, Echiura, Sipuncula, Studies on the origin and distribution of palytoxin in a Caribbean coral reef, A bioinformatics survey for conotoxin-like sequences in three turrid snail venom duct transcriptomes, Molecular diversity and gene evolution of the venom arsenal of terebridae predatory marine snails, Characterizing the molecular diversity and function of Terebridae venom, Trinity: recontructing a full-length transcriptome assembly without a genome from RNA-Seq data, De novo transcript sequence reconstruction from RNA-seq using the Trinity platform for reference generation and analysis, Modulation of host immune responses by nematode cystatins, Purification and characterization of gigantoxin-4, a new actinoporin from the sea anemone, The transcriptome of the zoanthid Protopalythoa variabilis (Cnidaria, Anthozoa) predicts a basal repertoire of toxin-like and venom-auxiliary polypeptides, Phylogeny of the serpin superfamily: implications of patterns of amino acid conservation for structure and function, A new multigene superfamily of Kunitz-type protease inhibitors from sea anemone, Tox-Prot, the toxin protein annotation program of the Swiss-Prot protein knowledgebase, The UniProtKB/Swiss-Prot Tox-Prot program: a central hub of integrated venom protein data, Colubrid venom composition: an -omics perspective, ConoServer, a database for conopeptide sequences and structures, ConoServer: updated content, knowledge, and discovery tools in the conopeptide database. Bootstrap support values are given for all nodes and clade names are indicated by colored squares. The CAP protein superfamily includes cysteine-rich secretory proteins (CRISPs), antigen 5 (Ag5), and pathogenesis-related 1 proteins (Pr-1) (Gibbs et al. Wash with soap and fresh water. 5. Carrying poison in their feet is a successful defense for fireworms. The fireworm CAP homologs cluster in a clade (although with no support) that includes the rest of the annelid sequences and a few arthropod sequences (supplementary fig. 2013). (2017) concluded that the intrachaetal cavity is artificial and found no evidence of associated venom glands, which led them to suggest that the physiological reactions triggered by fireworm stings result from direct injuries rather than venom injection. Venomous animals on the contrary, produce venom proteins endogenously by expressing specific gene products (Fry et al. Sequences from nonvenomous taxa are indicated with closed circles and fireworm homologs are highlighted in bold. 2017; Tilic et al. Seek medical treatment if … 2017). He said that he was waiting for a group of tourists at the beach when something stung his left foot. The bristles break off in human skin, ooze their toxin and cause a nasty rash. It has long been hypothesized that amphinomids are venomous and use the chaetae to inject a toxic substance. 2014b) and arthropods including remipede crustaceans, caterpillars, parasitoid wasps, and blood feeding insects like ticks and mosquitoes (Veiga et al. What’s Happening to Your High School Athlete. Cover the area with vinegar to neutralise the sting as soon as possible but if it is still causing irritation seek medical advice. (2017) found evidence of fluid being released from chaetal tips and identified grooved chaetae under the scanning electron microscope, indicating a possible alternative for toxin delivery. The following first aid treatment, based on current Australian research, is recommended for the stings of all The cDNA library was sequenced with Illumina HiSeq 1000 using a paired end flow cell and 80 x 2 cycle sequencing at the New York Genome Center. Transcripts initially identified as putative toxins were included in the final candidate toxin list only if 1) the best hit from the UniProtKB/Swiss-Prot database had a higher e-value than the initial hit from the venom database or HMM profile, or 2) the best hit from the UniProtKB/Swiss-Prot database was labeled as a toxin. 2006; Ribeiro et al. 2009). 2017). 2014b; Chmelař et al. Some of the fireworms, called bearded fireworms, are lined with fine white hairs. We have identified 12 serpins among the putative fireworm toxins that form a single orthologous cluster. He hid in the rocks all day. Venoms are among the most complex biochemical secretions known in nature, but despite this high complexity there is a remarkable degree of convergence in both the molecular scaffolds and the targets of venom components (Casewell et al. 2013; von Reumont et al. 2016) while glycerid bloodworms use a mixture of toxins to capture and immobilize prey (von Reumont et al. If this has helped you treat the sting, please remember to click the "accept" button, thanks. 2017), venom in segmented worms remains largely uncharacterized. very small, about an inch long. 2015). Treatment for a bristleworm bite or sting includes the following: Apply topical acetic acid (vinegar) or isopropyl alcohol. First aid: Remove bristles using tape. S3, Supplementary Material online) and interestingly, a particularly large clade that includes transcripts from all three fireworm species and two Glycera species also includes serine proteases identified from the posterior venom glands of the cephalopod Octopus kaurna (Fry et al. This evidence coupled with the uncertainty of a toxin delivery system may suggest that fireworms could be poisonous. Diagram of the bioinformatics pipeline followed to identify putative venom components in fireworms. Lastly, the partial paresthesia and numbness reported in the affected area is consistent with the expression of several neurotoxins (ShKT, spider toxins, and turripeptides) that can cause paralysis, block the neuromuscular transmission or function as anesthetics, and also contribute to the severe pain induced by fireworm stings. Despite their great diversity, the putative toxins identified are predominantly involved in three major biological processes: hemostasis, inflammatory response, and allergic reactions, all of which are commonly disrupted after fireworm stings. A golden fireworm sting may result in this: However, there is a small chance that a more dangerous species (the fire worm) made its way into your tank. In route, hold the bite site below the rest of the body, MH acknowledges funding from the Camille and Henry Dreyfus Teacher-Scholar Award and NSF awards CHE-1247550 and CHE-1228921. —Orthologous toxins in fireworms and associated functions. —Diversity of toxin homologs identified in each fireworm species. We have recovered 27 phospholipase-like genes that belong to two orthologous clusters, one of them corresponding to phospholipase B homologs and the other including phospholipase A2 homologs. Bearded fireworm (Busuf), Hermodice carunculata. Putative coding regions that included a signal peptide were extracted using a custom Perl script and analyzed following two different homology search strategies, namely sequence similarity searches using the BLASTP tool of the NCBI BLAST v2.6.0 package (Altschul 1997; Johnson et al. The fireworm is abundant on reefs, beneath stones in rocky areas or in seagrass beds, and on some muddy bottoms. 2009; Wong et al. A person becomes infected when they drink water that contains water fleas infected with guinea worm larvae. The three fireworms share a similar toxin profile, with C-type lectin being the most diverse toxin class in all cases, and peptidase S1, metalloproteinase M12, spider toxin, and CAP found among the most highly expressed toxin homologs, altogether representing ∼60% of all putative toxins identified (fig. 3). 2014). A roadmap to neglected venomous invertebrates, A polychaete’s powerful punch: venom gland transcriptomics of Glycera reveals a complex cocktail of toxin homologs, The first venomous crustacean revealed by transcriptomics and functional morphology: remipede venom glands express a unique toxin cocktail dominated by enzymes and a neurotoxin, Venomics of remipede crustaceans reveals novel peptide diversity and illuminates the venom’s biological role, The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system, Melt with this kiss: paralyzing and liquefying venom of the assassin bug, A spider-derived kunitz-type serine protease inhibitor that acts as a plasmin inhibitor and an elastase inhibitor. The following step is a homology search (blue) using three different search strategies based on BLAST, HMMER-sequence and HMMER-domain. Wikipedia came up with a creative suggestion on treatment of a fireworm sting. 2015; Huang et al. Venoms to drugs: venom as a source for the development of human therapeutics, Getting to the root of fireworms’ stinging chaetae—chaetal arrangement and ultrastructure of, Simukunin from the salivary glands of the black fly, Weaponization of a hormone: convergent recruitment of hyperglycemic hormone into the venom of arthropod predators, Evolutionary analysis of novel serine proteases in the Venom Gland transcriptome of, A catalog for the transcripts from the venomous structures of the caterpillar, From mollusks to medicine: a venomics approach for the discovery and characterization of therapeutics from terebridae peptide Toxins, Quo vadis venomics? 2008; Barroso et al. Bristleworms (or bristle worms) are segmented worms with bristly tufts extending from each of their segments. It delivers a powerful sting when threatened. It hurt like ---- for the rest of the day. Their suggestion is to take some adhesive tape (probably not duck tape :)) and put it over the affected area. 2013; Moran et al. Serpins regulate important proteolytic cascades involved in a variety of biological processes like coagulation, inflammation, and immune response (Law et al. Change ). It is a good idea to wear thick gloves when you have your hands in your tank anyway. Our results show that the species E. complanata, H. carunculata, and P. jeffreysii express a wide diversity of transcripts coding for toxin homologs that have been repeatedly recruited into animal venoms, including protease inhibitors, proteolytic enzymes, and neurotoxins (figs. 3 and 4). Kunitz-type inhibitors are ubiquitous serine protease inhibitors of approximately 60 amino acids with three conserved disulfide bridges that show inhibitory activity against trypsin, chymotrypsin, or both (Laskowski and Kato 1980; Wan et al. Specifically, the three species share a similar toxin profile with C-type lectins, peptidases, metalloproteinases, spider toxins, and CAP proteins found among the most highly expressed toxin homologs. This aggressive species doesn’t always wait until dark to eat. Lipocalins have also been identified as major allergens inducing severe anaphylactic reactions in humans after hematophagous insect bites (Paddock et al. Several annelid lineages use toxins for predation or defense (fig. 1), however apart from the widely studied salivary secretions of the hematophagous leech (fig. 1F) (Min et al. Modica MV, Lombardo F, Franchini P, Oliverio M. Perkin LC, Friesen KS, Flinn PW, Oppert B. Petersen TN, Brunak S, von Heijne G, Nielsen H. Ponce D, Brinkman DL, Potriquet J, Mulvenna J. Rokyta DR, Lemmon AR, Margres MJ, Aronow K. Teichert RW, Olivera BM, McIntosh JM, Bulaj G, Horvath MP. Remainder images (F and D) are publicly available under Creative Commons License. There's no effective treatment for these stings, but they aren't medically dangerous and eventually go away on their own. Handling a fireworm is a memorable experience. 2017), we provide compelling evidence suggesting that fireworms are venomous animals that use a complex mixture of toxins as a defensive mechanism. 2008). An individual of Hermodice carunculata was collected by SCUBA from Norman’s Pond Cay Cave, Norman’s Pond Cay, Exumas, Bahamas (GPS N 23 47.181, W 076 08.428) and transported back to the field station where it was flash frozen in liquid nitrogen. One is to prevent firing of any undischarged nematocysts remaining on the skin, thus preventing the injury from getting worse. 2008; Ottuso 2013; Haddad 2015; Schulze et al. Adapter sequences and low-quality reads were removed using Trimmomatic v0.36 (Bolger et al. 2011; von Reumont et al. The S1 family is the largest family of peptidases and includes serine proteases involved in a number of key biological processes, paramount among them are blood coagulation and immune responses (Page and Di Cera 2008). Sixteen lipocalin-like genes belonging to two orthologous clusters were identified in the H. carunculata, E. complanata, and P. jeffreysii transcriptomes. Lice feed by biting and drinking the blood of their hosts. However, if there is a risk a sting is from a Portuguese man-of-war, using a chemical can cause all of the stinging cells to fire at once and worsen the injury. Sequences from nonvenomous taxa are indicated with closed circles and fireworm homologs are highlighted in bold. 2016). 2014b) and from public databases as mentioned earlier. Among the neurotoxin homologs, we recovered transcripts with strong sequence similarity to conoidean neurotoxins, including two conotoxin-like peptides in E. complanata and four in P. jeffreysii, one teretoxin homolog in H. carunculata and two in E. complanata, and five turritoxin-like peptides in E. complanata. Phospholipases catalyze the hydrolysis of phospholipids generating free fatty acids and lysophospholipids, and thus inducing indirect hemolysis (Dennis 1983; Kini 2003). Venom gland components of the ectoparasitoid wasp, SignalP 4.0: discriminating signal peptides from transmembrane regions, Dietary breadth is positively correlated with venom complexity in cone snails, Insights into function and evolution of parasitoid wasp venoms. I hope you enjoy! 2015) was used to identify and annotate orthologous clusters among the fireworm toxin-like genes and inferred putative functions and biological activities that could explain the physiological symptoms observed after fireworm stings. 2013; Martinson et al. —Phylogeny of the family Amphinomidae and venomous annelid representatives. Kazal-type inhibitors act on a variety of serine proteases including thrombin, trypsin, factor XIIa, subtilisin A, elastase, chymotrypsin, and plasmin (Sigle and Ramalho-Ortigão 2013) and have been reported from the venoms of snakes and bats (Francischetti et al. 2008) against an in-house database that includes all known toxins available in public databases such as ConoServer (Kaas et al. 2012), scorpions and spiders (Yuan et al. The turripeptide-like toxins have a predicted signal sequence with high sequence identity to that of turripeptides and the same conserved cysteine pattern (fig. 10). 2013) was first used to predict protein-coding regions within transcripts. The putative kazal-type fireworm toxins are found in several clades across the tree, mainly clustering with kazal-type toxins recovered from the venom gland of Glycera bloodworms (von Reumont et al. 2014b). These worms have bristles with toxic tips, which inflict an incredibly painful sting. Bootstrap support values are given for all nodes and clade names are indicated by colored squares. The calcareous chaetae have been hypothesized to function as hypodermic needles that deliver an active toxin, which was identified as a trimethylammonium compound that causes strong skin irritation from the species Eurythoe complanata, and was consequently named Complanine (Nakamura et al. The tissue was homogenized in TriZol reagent (Life Technologies, NY) and total RNA was precipitated with isopropanol and dissolved in distilled water. Its venom provokes human reactions ranging from mild irritation to extreme pain and even death. 2008; Wang et al. Sequences from nonvenomous taxa are indicated with closed circles and fireworm homologs are highlighted in bold. We also identified several cytolysins homologs, including one actinoporin-like transcript from each transcriptome, 4 gigantoxin homologs from P. jeffreysii, and one latarcin-like peptide from of H. carunculata. Identifying the overlap of clusters of orthologous sequences across multiple species allows us to derive hypotheses about the function and evolution of proteins (Wang et al. Proteomics and deep sequencing comparison of seasonally active venom glands in the platypus reveals novel venom peptides and distinct expression profiles, Proteomic analysis of skin defensive factors of tree frog, Cloning and molecular characterization of BumaMPs1, a novel metalloproteinase from the venom of scorpion, Identification of novel tick salivary gland proteins for vaccine development, Structure and function of snake venom cysteine-rich secretory proteins, A venom serpin splicing isoform of the endoparasitoid wasp, A novel serine protease inhibitor from the venom of, Discovery of a distinct superfamily of kunitz-type toxin (KTT) from Tarantulas, InterProScan–an integration platform for the signature-recognition methods in InterPro, The C-type lectin-like domain superfamily. Neurotoxins of glycerid bloodworms use a complex mixture of toxins as a defensive mechanism toxin candidates is a venom! 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