Статті в журналах: "Cone snails"

1

Ebou, Anicet, Dominique Koua, Audrey Addablah, Solange Kakou-Ngazoa, and Sébastien Dutertre. "Combined Proteotranscriptomic-Based Strategy to Discover Novel Antimicrobial Peptides from Cone Snails." Biomedicines 9, no. 4 (March 29, 2021): 344. http://dx.doi.org/10.3390/biomedicines9040344.

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Despite their impressive diversity and already broad therapeutic applications, cone snail venoms have received less attention as a natural source in the investigation of antimicrobial peptides than other venomous animals such as scorpions, spiders, or snakes. Cone snails are among the largest genera (Conus sp.) of marine invertebrates, with more than seven hundred species described to date. These predatory mollusks use their sophisticated venom apparatus to capture prey or defend themselves. In-depth studies of these venoms have unraveled many biologically active peptides with pharmacological properties of interest in the field of pain management, the treatment of epilepsy, neurodegenerative diseases, and cardiac ischemia. Considering sequencing efficiency and affordability, cone snail venom gland transcriptome analyses could allow the discovery of new, promising antimicrobial peptides. We first present here the need for novel compounds like antimicrobial peptides as a viable alternative to conventional antibiotics. Secondly, we review the current knowledge on cone snails as a source of antimicrobial peptides. Then, we present the current state of the art in analytical methods applied to crude or milked venom followed by how antibacterial activity assay can be implemented for fostering cone snail antimicrobial peptides studies. We also propose a new innovative profile Hidden Markov model-based approach to annotate full venom gland transcriptomes and speed up the discovery of potentially active peptides from cone snails.

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2

Peraud, Olivier, Jason S. Biggs, Ronald W. Hughen, Alan R. Light, Gisela P. Concepcion, Baldomero M. Olivera, and Eric W. Schmidt. "Microhabitats within Venomous Cone Snails Contain Diverse Actinobacteria." Applied and Environmental Microbiology 75, no. 21 (September 11, 2009): 6820–26. http://dx.doi.org/10.1128/aem.01238-09.

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ABSTRACT Actinomycetes can be symbionts in diverse organisms, including both plants and animals. Some actinomycetes benefit their host by producing small molecule secondary metabolites; the resulting symbioses are often developmentally complex. Actinomycetes associated with three cone snails were studied. Cone snails are venomous tropical marine gastropods which have been extensively examined because of their production of peptide-based neurological toxins, but no microbiological studies have been reported on these organisms. A microhabitat approach was used in which dissected tissue from each snail was treated as an individual sample in order to explore bacteria in the tissues separately. Our results revealed a diverse, novel, and highly culturable cone snail-associated actinomycete community, with some isolates showing promising bioactivity in a neurological assay. This suggests that cone snails may represent an underexplored reservoir of novel actinomycetes of potential interest for drug discovery.

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3

Safavi-Hemami, Helena, Joanna Gajewiak, Santhosh Karanth, Samuel D. Robinson, Beatrix Ueberheide, Adam D. Douglass, Amnon Schlegel, et al. "Specialized insulin is used for chemical warfare by fish-hunting cone snails." Proceedings of the National Academy of Sciences 112, no. 6 (January 20, 2015): 1743–48. http://dx.doi.org/10.1073/pnas.1423857112.

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

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4

Wang, Hao, Xiaopeng Zhu, Yuepeng Liu, Sulan Luo, and Dongting Zhangsun. "Mitogenome Characterization of Four Conus Species and Comparative Analysis." International Journal of Molecular Sciences 24, no. 11 (May 28, 2023): 9411. http://dx.doi.org/10.3390/ijms24119411.

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Cone snails, as a type of marine organism, have rich species diversity. Traditionally, classifications of cone snails were based mostly on radula, shell, and anatomical characters. Because of these phenotypic features’ high population variability and propensity for local adaptation and convergence, identifying species can be difficult and occasionally inaccurate. In addition, mitochondrial genomes contain high phylogenetic information, so complete mitogenomes have been increasingly employed for inferring molecular phylogeny. To enrich the mitogenomic database of cone snails (Caenogastropoda: Conidae), mitogenomes of four Conus species, i.e., C. imperialis (15,505 bp), C. literatus (15,569 bp), C. virgo (15,594 bp), and C. marmoreus (15,579 bp), were characterized and compared. All 4 of these mitogenomes included 13 protein-coding genes, 2 ribosomal RNA genes, 22 tRNA genes, and non-coding regions. All the Protein Codon Genes (PCGs) of both newly sequenced mitogenomes used TAA or TAG as a terminal codon. Most PCGs used conventional start codon ATG, but an alternative initiation codon GTG was detected in a gene (NADH dehydrogenase subunit 4 (nad4)) of C. imperialis. In addition, the phylogenetic relationships were reconstructed among 20 Conus species on the basis of PCGs, COX1, and the complete mitogenome using both Bayesian Inference (BI) and Maximum Likelihood (ML). The phylogenetic results supported that C. litteratus, C. quercinus, and C. virgo were clustered together as a sister group (PP = 1, BS = 99), but they did not support the phylogenetic relation of C. imperialis and C. tribblei (PP = 0.79, BS = 50). In addition, our study established that PCGs and complete mitogenome are the two useful markers for phylogenetic inference of Conus species. These results enriched the data of the cone snail’s mitochondrion in the South China Sea and provided a reliable basis for the interpretation of the phylogenetic relationship of the cone snail based on the mitochondrial genome.

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5

Chivian, E. "The Threat to Cone Snails." Science 302, no. 5644 (October 17, 2003): 391b—391. http://dx.doi.org/10.1126/science.302.5644.391b.

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6

Park, Youmie. "Mining Invertebrate Natural Products for Future Therapeutic Treasure." Natural Product Communications 6, no. 9 (September 2011): 1934578X1100600. http://dx.doi.org/10.1177/1934578x1100600944.

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This review focuses on biologically active entities from invertebrate sources, especially snails. The reader will encounter several categories of compounds from snails including glycosaminoglycans, peptides, proteins (glycoproteins), and enzymes which possess diverse biological activities. Among glycosaminoglycans, acharan sulfate which was isolated from a giant African snail Acahtina fulica is reviewed extensively. Conotoxins which are also called conopeptides are unique peptide mixtures from marine cone snail. Conotoxins are secreted to capture its prey, and currently have the potential to be highly effective drug candidates. One of the conotoxins is now in the market as a pain killer. Proteins as well as glycoproteins in the snail are known to be involved in the host defense process from an attack of diverse pathogens. Carbohydrate-degrading enzymes characterized and purified in snails are introduced to give an insight into the applicability in glycobiology research such as synthesis and structure characterization of glycoconjugates. It seems that simple snails produce very complicated biological compounds which could be an invaluable source in future therapeutics as well as research areas in natural medicine.

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7

Jin, Ai-Hua, Mathilde R. Israel, Marco C. Inserra, Jennifer J. Smith, Richard J. Lewis, Paul F. Alewood, Irina Vetter та Sébastien Dutertre. "δ-Conotoxin SuVIA suggests an evolutionary link between ancestral predator defence and the origin of fish-hunting behaviour in carnivorous cone snails". Proceedings of the Royal Society B: Biological Sciences 282, № 1811 (22 липня 2015): 20150817. http://dx.doi.org/10.1098/rspb.2015.0817.

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Some venomous cone snails feed on small fishes using an immobilizing combination of synergistic venom peptides that target K v and Na v channels. As part of this envenomation strategy, δ-conotoxins are potent ichtyotoxins that enhance Na v channel function. δ-Conotoxins belong to an ancient and widely distributed gene superfamily, but any evolutionary link from ancestral worm-eating cone snails to modern piscivorous species has not been elucidated. Here, we report the discovery of SuVIA, a potent vertebrate-active δ-conotoxin characterized from a vermivorous cone snail ( Conus suturatus ). SuVIA is equipotent at hNa V 1.3, hNa V 1.4 and hNa V 1.6 with EC 50 s in the low nanomolar range. SuVIA also increased peak hNa V 1.7 current by approximately 75% and shifted the voltage-dependence of activation to more hyperpolarized potentials from –15 mV to –25 mV, with little effect on the voltage-dependence of inactivation. Interestingly, the proximal venom gland expression and pain-inducing effect of SuVIA in mammals suggest that δ-conotoxins in vermivorous cone snails play a defensive role against higher order vertebrates. We propose that δ-conotoxins originally evolved in ancestral vermivorous cones to defend against larger predators including fishes have been repurposed to facilitate a shift to piscivorous behaviour, suggesting an unexpected underlying mechanism for this remarkable evolutionary transition.

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8

Joo, Soyoun, Sunghwan Jung, Sungyon Lee, Robert H. Cowie, and Daisuke Takagi. "Freshwater snail feeding: lubrication-based particle collection on the water surface." Journal of The Royal Society Interface 17, no. 165 (April 2020): 20200139. http://dx.doi.org/10.1098/rsif.2020.0139.

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The means by which aquatic animals such as freshwater snails collect food particles distributed on the water surface are of great interest for understanding life at the air–water interface. The apple snail Pomacea canaliculata stabilizes itself just below the air–water interface and manipulates its foot such that it forms a cone-shaped funnel into which an inhalant current is generated, thereby drawing food particles into the funnel to be ingested. We measured the velocity of this feeding current and tracked the trajectories of food particles around and on the snail. Our experiments indicated that the particles were collected via the free surface flow generated by the snail’s undulating foot. The findings were interpreted using a simple model based on lubrication theory, which considered several plausible mechanisms depending on the relative importance of hydrostatic pressure, capillary action and rhythmic surface undulation.

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9

Morales Duque, Harry, Simoni Campos Dias, and Octávio Luiz Franco. "Structural and Functional Analyses of Cone Snail Toxins." Marine Drugs 17, no. 6 (June 21, 2019): 370. http://dx.doi.org/10.3390/md17060370.

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Cone snails are marine gastropod mollusks with one of the most powerful venoms in nature. The toxins, named conotoxins, must act quickly on the cone snails´ prey due to the fact that snails are extremely slow, reducing their hunting capability. Therefore, the characteristics of conotoxins have become the object of investigation, and as a result medicines have been developed or are in the trialing process. Conotoxins interact with transmembrane proteins, showing specificity and potency. They target ion channels and ionotropic receptors with greater regularity, and when interaction occurs, there is immediate physiological decompensation. In this review we aimed to evaluate the structural features of conotoxins and the relationship with their target types.

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10

O’Brien, Henrik, Shingo Kanemura, Masaki Okumura, Robert Baskin, Pradip Bandyopadhyay, Baldomero Olivera, Lars Ellgaard, Kenji Inaba, and Helena Safavi-Hemami. "Ero1-Mediated Reoxidation of Protein Disulfide Isomerase Accelerates the Folding of Cone Snail Toxins." International Journal of Molecular Sciences 19, no. 11 (October 31, 2018): 3418. http://dx.doi.org/10.3390/ijms19113418.

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Disulfide-rich peptides are highly abundant in nature and their study has provided fascinating insight into protein folding, structure and function. Venomous cone snails belong to a group of organisms that express one of the largest sets of disulfide-rich peptides (conotoxins) found in nature. The diversity of structural scaffolds found for conotoxins suggests that specialized molecular adaptations have evolved to ensure their efficient folding and secretion. We recently showed that canonical protein disulfide isomerase (PDI) and a conotoxin-specific PDI (csPDI) are ubiquitously expressed in the venom gland of cone snails and play a major role in conotoxin folding. Here, we identify cone snail endoplasmic reticulum oxidoreductin-1 (Conus Ero1) and investigate its role in the oxidative folding of conotoxins through reoxidation of cone snail PDI and csPDI. We show that Conus Ero1 preferentially reoxidizes PDI over csPDI, suggesting that the reoxidation of csPDI may rely on an Ero1-independent molecular pathway. Despite the preferential reoxidation of PDI over csPDI, the combinatorial effect of Ero1 and csPDI provides higher folding yields than Ero1 and PDI. We further demonstrate that the highest in vitro folding rates of two model conotoxins are achieved when all three enzymes are present, indicating that these enzymes may act synergistically. Our findings provide new insight into the generation of one of the most diverse classes of disulfide-rich peptides and may improve current in vitro approaches for the production of venom peptides for pharmacological studies.

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11

Celia Henry Arnaud. "Cone snails lure prey with faux pheromones." C&EN Global Enterprise 99, no. 9 (March 15, 2021): 9. http://dx.doi.org/10.1021/cen-09909-scicon9.

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12

Santhana Ramasamy, M., and S. Manikandan. "Novel Pharmacological Targets From Indian Cone Snails." Mini-Reviews in Medicinal Chemistry 11, no. 2 (February 1, 2011): 125–30. http://dx.doi.org/10.2174/138955711794519500.

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13

Duda, T. F. "How Much at Risk Are Cone Snails?" Science 303, no. 5660 (February 13, 2004): 955–57. http://dx.doi.org/10.1126/science.303.5660.955.

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14

Olivera, B., W. Gray, R. Zeikus, J. McIntosh, J. Varga, J. Rivier, V. de Santos, and L. Cruz. "Peptide neurotoxins from fish-hunting cone snails." Science 230, no. 4732 (December 20, 1985): 1338–43. http://dx.doi.org/10.1126/science.4071055.

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15

Möller, Carolina, та Frank Marí. "A vasopressin/oxytocin-related conopeptide with γ-carboxyglutamate at position 8". Biochemical Journal 404, № 3 (29 травня 2007): 413–19. http://dx.doi.org/10.1042/bj20061480.

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Vasopressins and oxytocins are homologous, ubiquitous and multifunctional peptides present in animals. Conopressins are vasopressin/oxytocin-related peptides that have been found in the venom of cone snails, a genus of marine predatory molluscs that envenom their prey with a complex mixture of neuroactive peptides. In the present paper, we report the purification and characterization of a unique conopressin isolated from the venom of Conus villepinii, a vermivorous cone snail species from the western Atlantic Ocean. This novel peptide, designated γ-conopressin-vil, has the sequence CLIQDCPγG* (γ is γ-carboxyglutamate and * is C-terminal amidation). The unique feature of this vasopressin/oxytocin-like peptide is that the eighth residue is γ-carboxyglutamate instead of a neutral or basic residue; therefore it could not be directly classified into either the vasopressin or the oxytocin peptide families. Nano-NMR spectroscopy of the peptide isolated directly from the cone snails revealed that the native γ-conopressin-vil undergoes structural changes in the presence of calcium. This suggests that the peptide binds calcium, and the calcium-binding process is mediated by the γ-carboxyglutamate residue. However, the negatively charged residues in the sequence of γ-conopressin-vil may mediate calcium binding by a novel mechanism not observed in other peptides of this family.

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16

Aman, Joseph W., Julita S. Imperial, Beatrix Ueberheide, Min-Min Zhang, Manuel Aguilar, Dylan Taylor, Maren Watkins, et al. "Insights into the origins of fish hunting in venomous cone snails from studies of Conus tessulatus." Proceedings of the National Academy of Sciences 112, no. 16 (April 6, 2015): 5087–92. http://dx.doi.org/10.1073/pnas.1424435112.

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

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17

Abraham, Nikita, and Richard Lewis. "Neuronal Nicotinic Acetylcholine Receptor Modulators from Cone Snails." Marine Drugs 16, no. 6 (June 13, 2018): 208. http://dx.doi.org/10.3390/md16060208.

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18

Abalde, Samuel, Manuel J. Tenorio, Carlos M. L. Afonso, and Rafael Zardoya. "Mitogenomic phylogeny of cone snails endemic to Senegal." Molecular Phylogenetics and Evolution 112 (July 2017): 79–87. http://dx.doi.org/10.1016/j.ympev.2017.04.020.

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19

Prashanth, Jutty Rajan, Sebastien Dutertre, Subash Kumar Rai, and Richard J. Lewis. "Venomics Reveals a Non-Compartmentalised Venom Gland in the Early Diverged Vermivorous Conus distans." Toxins 14, no. 3 (March 19, 2022): 226. http://dx.doi.org/10.3390/toxins14030226.

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The defensive use of cone snail venom is hypothesised to have first arisen in ancestral worm-hunting snails and later repurposed in a compartmentalised venom duct to facilitate the dietary shift to molluscivory and piscivory. Consistent with its placement in a basal lineage, we demonstrate that the C. distans venom gland lacked distinct compartmentalisation. Transcriptomics revealed C. distans expressed a wide range of structural classes, with inhibitory cysteine knot (ICK)-containing peptides dominating. To better understand the evolution of the venom gland compartmentalisation, we compared C. distans to C. planorbis, the earliest diverging species from which a defence-evoked venom has been obtained, and fish-hunting C. geographus from the Gastridium subgenus that injects distinct defensive and predatory venoms. These comparisons support the hypothesis that venom gland compartmentalisation arose in worm-hunting species and enabled repurposing of venom peptides to facilitate the dietary shift from vermivory to molluscivory and piscivory in more recently diverged cone snail lineages.

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20

Prashanth, Jutty Rajan, Sebastien Dutertre, and Richard James Lewis. "Pharmacology of predatory and defensive venom peptides in cone snails." Molecular BioSystems 13, no. 12 (2017): 2453–65. http://dx.doi.org/10.1039/c7mb00511c.

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Cone snails use distinct venoms for defence and prey capture. The pharmacology of these neurotoxic peptides have been extensively studied for pharmacological probes, venom evolution mechanisms and potential therapeutics.

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21

Becker, Stefan, and Heinrich Terlau. "Toxins from cone snails: properties, applications and biotechnological production." Applied Microbiology and Biotechnology 79, no. 1 (May 2008): 1–9. http://dx.doi.org/10.1007/s00253-008-1385-6.

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22

Turner, Ashlin, Quentin Kaas, and David J. Craik. "Hormone-like conopeptides – new tools for pharmaceutical design." RSC Medicinal Chemistry 11, no. 11 (2020): 1235–51. http://dx.doi.org/10.1039/d0md00173b.

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23

Yao, Ge, Chao Peng, Yabing Zhu, Chongxu Fan, Hui Jiang, Jisheng Chen, Ying Cao, and Qiong Shi. "High-Throughput Identification and Analysis of Novel Conotoxins from Three Vermivorous Cone Snails by Transcriptome Sequencing." Marine Drugs 17, no. 3 (March 26, 2019): 193. http://dx.doi.org/10.3390/md17030193.

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The venom of each Conus species consists of a diverse array of neurophysiologically active peptides, which are mostly unique to the examined species. In this study, we performed high-throughput transcriptome sequencing to extract and analyze putative conotoxin transcripts from the venom ducts of 3 vermivorous cone snails (C. caracteristicus, C. generalis, and C. quercinus), which are resident in offshore waters of the South China Sea. In total, 118, 61, and 48 putative conotoxins (across 22 superfamilies) were identified from the 3 Conus species, respectively; most of them are novel, and some possess new cysteine patterns. Interestingly, a series of 45 unassigned conotoxins presented with a new framework of C-C-C-C-C-C, and their mature regions were sufficiently distinct from any other known conotoxins, most likely representing a new superfamily. O- and M-superfamily conotoxins were the most abundant in transcript number and transcription level, suggesting their critical roles in the venom functions of these vermivorous cone snails. In addition, we identified numerous functional proteins with potential involvement in the biosynthesis, modification, and delivery process of conotoxins, which may shed light on the fundamental mechanisms for the generation of these important conotoxins within the venom duct of cone snails.

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24

West, Peter J., Grzegorz Bulaj та Doju Yoshikami. "Effects of δ-Conotoxins PVIA and SVIE on Sodium Channels in the Amphibian Sympathetic Nervous System". Journal of Neurophysiology 94, № 6 (грудень 2005): 3916–24. http://dx.doi.org/10.1152/jn.01304.2004.

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δ-Conotoxins are a family of small, disulfide-rich peptides found in the venoms of predatory cone snails ( Conus). We examined in detail the effects of δ-conotoxin PVIA from the fish hunting cone snail Conus purpurascens on sodium currents in dissociated sympathetic neurons from the leopard frog Rana pipiens. We also compared this toxin’s effects with those of δ-conotoxin SVIE from Conus striatus, another piscivorous cone snail. d-PVIA slowed the time-course of inactivation of δ sodium currents and shifted the voltage-dependence of activation and steady-state inactivation to more hyperpolarized potentials. Similar, albeit more pronounced, effects were seen with d-SVIE. While the effects of d-PVIA were reversed by washing, those of d-SVIE were largely irreversible over the time-course of these experiments. The effects of d-PVIA could be suppressed by conditioning depolarizations in a voltage- and time-dependent manner, whereas the effects of d-SVIE were largely resistant to conditioning depolarizations. Last, in intact sympathetic nervous system preparations, d-PVIA inhibited evoked trains of compound action potentials. Many of these effects of d-PVIA and d-SVIE are remarkably similar to those of toxins that bind to site 3 on voltage-gated sodium channels.

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25

Fu, Ying, Cheng Li, Shuai Dong, Yong Wu, Dongting Zhangsun, and Sulan Luo. "Discovery Methodology of Novel Conotoxins from Conus Species." Marine Drugs 16, no. 11 (October 30, 2018): 417. http://dx.doi.org/10.3390/md16110417.

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Cone snail venoms provide an ideal resource for neuropharmacological tools and drug candidates discovery, which have become a research hotspot in neuroscience and new drug development. More than 1,000,000 natural peptides are produced by cone snails, but less than 0.1% of the estimated conotoxins has been characterized to date. Hence, the discovery of novel conotoxins from the huge conotoxin resources with high-throughput and sensitive methods becomes a crucial key for the conotoxin-based drug development. In this review, we introduce the discovery methodology of new conotoxins from various Conus species. It focuses on obtaining full N- to C-terminal sequences, regardless of disulfide bond connectivity through crude venom purification, conotoxin precusor gene cloning, venom duct transcriptomics, venom proteomics and multi-omic methods. The protocols, advantages, disadvantages, and developments of different approaches during the last decade are summarized and the promising prospects are discussed as well.

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26

Puillandre, N., P. Bouchet, T. F. Duda, S. Kauferstein, A. J. Kohn, B. M. Olivera, M. Watkins, and C. Meyer. "Molecular phylogeny and evolution of the cone snails (Gastropoda, Conoidea)." Molecular Phylogenetics and Evolution 78 (September 2014): 290–303. http://dx.doi.org/10.1016/j.ympev.2014.05.023.

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27

Robinson, Samuel D., Qing Li, Pradip K. Bandyopadhyay, Joanna Gajewiak, Mark Yandell, Anthony T. Papenfuss, Anthony W. Purcell, Raymond S. Norton, and Helena Safavi-Hemami. "Hormone-like peptides in the venoms of marine cone snails." General and Comparative Endocrinology 244 (April 2017): 11–18. http://dx.doi.org/10.1016/j.ygcen.2015.07.012.

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28

Dutt, Mriga, Jean Giacomotto, Lotten Ragnarsson, Asa Andersson, Andreas Brust, Zoltan Deakan, Paul F. Alewood, and Richard J. Lewis. "Re-evaluating the nirvana cabal deployed by piscivorous cone snails." Toxicon 177 (April 2020): S9—S10. http://dx.doi.org/10.1016/j.toxicon.2019.10.044.

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29

Kauferstein, Silke, Christine Porth, Yvonne Kendel, Cora Wunder, Annette Nicke, Dusan Kordis, Philippe Favreau, Dominique Koua, Reto Stöcklin, and Dietrich Mebs. "Venomic study on cone snails (Conus spp.) from South Africa." Toxicon 57, no. 1 (January 2011): 28–34. http://dx.doi.org/10.1016/j.toxicon.2010.09.009.

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30

Fedosov, Alexander, Paul Zaharias, and Nicolas Puillandre. "A phylogeny-aware approach reveals unexpected venom components in divergent lineages of cone snails." Proceedings of the Royal Society B: Biological Sciences 288, no. 1954 (July 7, 2021): 20211017. http://dx.doi.org/10.1098/rspb.2021.1017.

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Marine gastropods of the genus Conus are renowned for their remarkable diversity and deadly venoms. While Conus venoms are increasingly well studied for their biomedical applications, we know surprisingly little about venom composition in other lineages of Conidae. We performed comprehensive venom transcriptomic profiling for Conasprella coriolisi and Pygmaeconus traillii , first time for both respective genera. We complemented reference-based transcriptome annotation by a de novo toxin prediction guided by phylogeny, which involved transcriptomic data on two additional ‘divergent’ cone snail lineages, Profundiconus , and Californiconus . We identified toxin clusters (SSCs) shared among all or some of the four analysed genera based on the identity of the signal region—a molecular tag present in toxins. In total, 116 and 98 putative toxins represent 29 and 28 toxin gene superfamilies in Conasprella and Pygmaeconus , respectively; about quarter of these only found by semi-manual annotation of the SSCs. Two rare gene superfamilies, originally identified from fish-hunting cone snails, were detected outside Conus rather unexpectedly, so we further investigated their distribution across Conidae radiation. We demonstrate that both these, in fact, are ubiquitous in Conidae, sometimes with extremely high expression. Our findings demonstrate how a phylogeny-aware approach circumvents methodological caveats of similarity-based transcriptome annotation.

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31

Giglio, Matías L., Paula Flórez Salcedo, Maren Watkins, and Baldomero Olivera. "Insights into a putative polychaete-gastropod symbiosis from a newly identified annelid worm that predates upon Conus ermineus eggs." Contributions to Zoology 92, no. 2 (February 17, 2023): 97–111. http://dx.doi.org/10.1163/18759866-bja10038.

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Abstract Cone snails are a diverse group of venomous marine gastropods that have dioecious reproduction and internal fertilization resulting in egg deposition inside capsules. However, the observational studies conducted on their spawning behaviour and egg masses have left many open questions. Here, we analyse egg masses from a specimen of Conus ermineus kept in captivity for over 17 years. We present the first detailed description of the morphological features of the egg capsules and eggs (e.g., egg shape, size, and colour). The analysis of these capsules led us to the identification of a dinophilid worm (Polychaeta: Dinophilidae) living inside the snail egg capsules and likely feeding upon the snail eggs. This is the first report of such behaviours among dinophilids. Our analysis suggests that these worms belong to a new species, here described as Dimorphilus oophagus sp. nov., supported by both molecular and morphological data. Finally, we discuss the possibility of a putative symbiotic relationship between the worm and the snail.

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32

Bernáldez-Sarabia, Johanna, Andrea Figueroa-Montiel, Salvador Dueñas, Karla Cervantes-Luévano, Jesús Beltrán, Ernesto Ortiz, Samanta Jiménez, et al. "The Diversified O-Superfamily in Californiconus californicus Presents a Conotoxin with Antimycobacterial Activity." Toxins 11, no. 2 (February 20, 2019): 128. http://dx.doi.org/10.3390/toxins11020128.

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Californiconus californicus, previously named Conus californicus, has always been considered a unique species within cone snails, because of its molecular, toxicological and morphological singularities; including the wide range of its diet, since it is capable of preying indifferently on fish, snails, octopus, shrimps, and worms. We report here a new cysteine pattern conotoxin assigned to the O1-superfamily capable of inhibiting the growth of Mycobacterium tuberculosis (Mtb). The conotoxin was tested on a pathogen reference strain (H37Rv) and multidrug-resistant strains, having an inhibition effect on growth with a minimal inhibitory concentration (MIC) range of 3.52–0.22 μM, similar concentrations to drugs used in clinics. The peptide was purified from the venom using reverse phase high-performance liquid chromatography (RP-HPLC), a partial sequence was constructed by Edman degradation, completed by RACE and confirmed with venom gland transcriptome. The 32-mer peptide containing eight cysteine residues was named O1_cal29b, according to the current nomenclature for this type of molecule. Moreover, transcriptomic analysis of O-superfamily toxins present in the venom gland of the snail allowed us to assign several signal peptides to O2 and O3 superfamilies not described before in C. californicus, with new conotoxins frameworks.

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33

Hendricks, Jonathan R. "Diversity and preserved shell coloration patterns of Miocene Conidae (Neogastropoda) from an exposure of the Gatun Formation, Colón Province, Panama." Journal of Paleontology 92, no. 5 (May 24, 2018): 804–37. http://dx.doi.org/10.1017/jpa.2017.153.

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AbstractExtant members of the neogastropod family Conidae (cone snails) are renowned for their often dazzling shell coloration patterns and venomous feeding habits. Many cone snail species have also been described from the fossil record, but to date have been little used to understand the evolutionary history of extant clades. The cone snail fauna of the Miocene Gatun Formation of Colón Province, Panama is especially important for understanding the temporal and biogeographic history of tropical American Conidae. Intensive, focused collecting from an exposure of the lower Gatun Formation (deposited ca. 11–10 Ma) resulted in the discovery of nearly 900 specimens of Conidae. Remarkably, many of these well-preserved specimens exhibit revealed coloration patterns when exposed to ultraviolet light. The fluorescing coloration patterns were used in conjunction with other features of shell morphology to differentiate species and, in most cases, evaluate their potential relationships to members of the extant tropical American fauna. Nine species are fully described from this locality, one of which is recognized as new:Conus(Stephanoconus)woodringin. sp. At least one, and perhaps more, additional Conidae species are also present at the study locality. The diversity of this Conidae fauna is considered moderate relative to other recently analyzed tropical American fossil assemblages. The phylogenetic diversity of the assemblage, however, is noteworthy: six of the ten species can be confidently assigned to six different clades of extant Conidae, providing potentially useful calibration points for future phylogenetic studies.http://zoobank.org/8fe00c31-8f3f-4514-85af-29068e468cd3

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34

Gao, Bingmiao, Chao Peng, Jiaan Yang, Yunhai Yi, Junqing Zhang, and Qiong Shi. "Cone Snails: A Big Store of Conotoxins for Novel Drug Discovery." Toxins 9, no. 12 (December 7, 2017): 397. http://dx.doi.org/10.3390/toxins9120397.

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35

Safavi-Hemami, Helena, Aiping Lu, Qing Li, Alexander E. Fedosov, Jason Biggs, Patrice Showers Corneli, Jon Seger, Mark Yandell, and Baldomero M. Olivera. "Venom Insulins of Cone Snails Diversify Rapidly and Track Prey Taxa." Molecular Biology and Evolution 33, no. 11 (August 14, 2016): 2924–34. http://dx.doi.org/10.1093/molbev/msw174.

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36

Espiritu, Doris Joy D., Maren Watkins, Virginia Dia-Monje, G. Edward Cartier, Lourdes J. Cruz, and Baldomero M. Olivera. "Venomous cone snails: molecular phylogeny and the generation of toxin diversity." Toxicon 39, no. 12 (December 2001): 1899–916. http://dx.doi.org/10.1016/s0041-0101(01)00175-1.

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37

Olivera, Baldomero M., David R. Hillyard, Maren Marsh, and Doju Yoshikami. "Combinatorial peptide libraries in drug design: lessons from venomous cone snails." Trends in Biotechnology 13, no. 10 (October 1995): 422–26. http://dx.doi.org/10.1016/s0167-7799(00)88996-9.

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38

Olivera, Baldomero M. "Linking venoms to behavior: Fish-hunting cone snails, a case study." Toxicon 158 (February 2019): S33. http://dx.doi.org/10.1016/j.toxicon.2018.10.116.

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39

Neves, Jorge L. B., Julita S. Imperial, David Morgenstern, Beatrix Ueberheide, Joanna Gajewiak, Agostinho Antunes, Samuel D. Robinson, et al. "Characterization of the First Conotoxin from Conus ateralbus, a Vermivorous Cone Snail from the Cabo Verde Archipelago." Marine Drugs 17, no. 8 (July 24, 2019): 432. http://dx.doi.org/10.3390/md17080432.

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Conus ateralbus is a cone snail endemic to the west side of the island of Sal, in the Cabo Verde Archipelago off West Africa. We describe the isolation and characterization of the first bioactive peptide from the venom of this species. This 30AA venom peptide is named conotoxin AtVIA (δ-conotoxin-like). An excitatory activity was manifested by the peptide on a majority of mouse lumbar dorsal root ganglion neurons. An analog of AtVIA with conservative changes on three amino acid residues at the C-terminal region was synthesized and this analog produced an identical effect on the mouse neurons. AtVIA has homology with δ-conotoxins from other worm-hunters, which include conserved sequence elements that are shared with δ-conotoxins from fish-hunting Conus. In contrast, there is no comparable sequence similarity with δ-conotoxins from the venoms of molluscivorous Conus species. A rationale for the potential presence of δ-conotoxins, that are potent in vertebrate systems in two different lineages of worm-hunting cone snails, is discussed.

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40

Gao, Bingmiao, Yu Huang, Chao Peng, Bo Lin, Yanling Liao, Chao Bian, Jiaan Yang, and Qiong Shi. "High-Throughput Prediction and Design of Novel Conopeptides for Biomedical Research and Development." BioDesign Research 2022 (November 7, 2022): 1–14. http://dx.doi.org/10.34133/2022/9895270.

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Cone snail venoms have been considered a valuable treasure for international scientists and businessmen, mainly due to their pharmacological applications in development of marine drugs for treatment of various human diseases. To date, around 800 Conus species are recorded, and each of them produces over 1,000 venom peptides (termed as conopeptides or conotoxins). This reflects the high diversity and complexity of cone snails, although most of their venoms are still uncharacterized. Advanced multiomics (such as genomics, transcriptomics, and proteomics) approaches have been recently developed to mine diverse Conus venom samples, with the main aim to predict and identify potentially interesting conopeptides in an efficient way. Some bioinformatics techniques have been applied to predict and design novel conopeptide sequences, related targets, and their binding modes. This review provides an overview of current knowledge on the high diversity of conopeptides and multiomics advances in high-throughput prediction of novel conopeptide sequences, as well as molecular modeling and design of potential drugs based on the predicted or validated interactions between these toxins and their molecular targets.

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41

Olivera, Baldomero M. "A Serendipitous Path to Pharmacology." Annual Review of Pharmacology and Toxicology 61, no. 1 (January 6, 2021): 9–23. http://dx.doi.org/10.1146/annurev-pharmtox-030320-113510.

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My path to research in neuropharmacology has been a coalescing of my training as a molecular biologist and my intense interest in an esoteric group of animals, the fish-hunting cone snails. Attempting to bridge these two disparate worlds has led me to an idiosyncratic career as a pharmacologist.

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Fassio, Giulia, Maria Vittoria Modica, Lou Mary, Paul Zaharias, Alexander E. Fedosov, Juliette Gorson, Yuri I. Kantor, Mandё Holford, and Nicolas Puillandre. "Venom Diversity and Evolution in the Most Divergent Cone Snail Genus Profundiconus." Toxins 11, no. 11 (October 28, 2019): 623. http://dx.doi.org/10.3390/toxins11110623.

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Profundiconus is the most divergent cone snail genus and its unique phylogenetic position, sister to the rest of the family Conidae, makes it a key taxon for examining venom evolution and diversity. Venom gland and foot transcriptomes of Profundiconus cf. vaubani and Profundiconus neocaledonicus were de novo assembled, annotated, and analyzed for differential expression. One hundred and thirty-seven venom components were identified from P. cf. vaubani and 82 from P. neocaledonicus, with only four shared by both species. The majority of the transcript diversity was composed of putative peptides, including conotoxins, profunditoxins, turripeptides, insulin, and prohormone-4. However, there were also a significant percentage of other putative venom components such as chymotrypsin and L-rhamnose-binding lectin. The large majority of conotoxins appeared to be from new gene superfamilies, three of which are highly different from previously reported venom peptide toxins. Their low conotoxin diversity and the type of insulin found suggested that these species, for which no ecological information are available, have a worm or molluscan diet associated with a narrow dietary breadth. Our results indicate that Profundiconus venom is highly distinct from that of other cone snails, and therefore important for examining venom evolution in the Conidae family.

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43

Ueberheide, Beatrix M., David Fenyö, Paul F. Alewood, and Brian T. Chait. "Rapid sensitive analysis of cysteine rich peptide venom components." Proceedings of the National Academy of Sciences 106, no. 17 (April 20, 2009): 6910–15. http://dx.doi.org/10.1073/pnas.0900745106.

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Disulfide-rich peptide venoms from animals such as snakes, spiders, scorpions, and certain marine snails represent one of nature's great diversity libraries of bioactive molecules. The various species of marine cone shells have alone been estimated to produce >50,000 distinct peptide venoms. These peptides have stimulated considerable interest because of their ability to potently alter the function of specific ion channels. To date, only a small fraction of this immense resource has been characterized because of the difficulty in elucidating their primary structures, which range in size between 10 and 80 aa, include up to 5 disulfide bonds, and can contain extensive posttranslational modifications. The extraordinary complexity of crude venoms and the lack of DNA databases for many of the organisms of interest present major analytical challenges. Here, we describe a strategy that uses mass spectrometry for the elucidation of the mature peptide toxin components of crude venom samples. Key to this strategy is our use of electron transfer dissociation (ETD), a mass spectrometric fragmentation technique that can produce sequence information across the entire peptide backbone. However, because ETD only yields comprehensive sequence coverage when the charge state of the precursor peptide ion is sufficiently high and the m/z ratio is low, we combined ETD with a targeted chemical derivatization strategy to increase the charge state of cysteine-containing peptide toxins. Using this strategy, we obtained full sequences for 31 peptide toxins, using just 7% of the crude venom from the venom gland of a single cone snail (Conus textile).

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44

Bjørn-Yoshimoto, Walden E., Iris Bea L. Ramiro, Mark Yandell, J. Michael McIntosh, Baldomero M. Olivera, Lars Ellgaard, and Helena Safavi-Hemami. "Curses or Cures: A Review of the Numerous Benefits Versus the Biosecurity Concerns of Conotoxin Research." Biomedicines 8, no. 8 (July 22, 2020): 235. http://dx.doi.org/10.3390/biomedicines8080235.

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Conotoxins form a diverse group of peptide toxins found in the venom of predatory marine cone snails. Decades of conotoxin research have provided numerous measurable scientific and societal benefits. These include their use as a drug, diagnostic agent, drug leads, and research tools in neuroscience, pharmacology, biochemistry, structural biology, and molecular evolution. Human envenomations by cone snails are rare but can be fatal. Death by envenomation is likely caused by a small set of toxins that induce muscle paralysis of the diaphragm, resulting in respiratory arrest. The potency of these toxins led to concerns regarding the potential development and use of conotoxins as biological weapons. To address this, various regulatory measures have been introduced that limit the use and access of conotoxins within the research community. Some of these regulations apply to all of the ≈200,000 conotoxins predicted to exist in nature of which less than 0.05% are estimated to have any significant toxicity in humans. In this review we provide an overview of the many benefits of conotoxin research, and contrast these to the perceived biosecurity concerns of conotoxins and research thereof.

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45

Jin, Ai-Hua, Sébastien Dutertre, Mriga Dutt, Vincent Lavergne, Alun Jones, Richard Lewis, and Paul Alewood. "Transcriptomic-Proteomic Correlation in the Predation-Evoked Venom of the Cone Snail, Conus imperialis." Marine Drugs 17, no. 3 (March 19, 2019): 177. http://dx.doi.org/10.3390/md17030177.

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Individual variation in animal venom has been linked to geographical location, feeding habit, season, size, and gender. Uniquely, cone snails possess the remarkable ability to change venom composition in response to predatory or defensive stimuli. To date, correlations between the venom gland transcriptome and proteome within and between individual cone snails have not been reported. In this study, we use 454 pyrosequencing and mass spectrometry to decipher the transcriptomes and proteomes of the venom gland and corresponding predation-evoked venom of two specimens of Conus imperialis. Transcriptomic analyses revealed 17 conotoxin gene superfamilies common to both animals, including 5 novel superfamilies and two novel cysteine frameworks. While highly expressed transcripts were common to both specimens, variation of moderately and weakly expressed precursor sequences was surprisingly diverse, with one specimen expressing two unique gene superfamilies and consistently producing more paralogs within each conotoxin gene superfamily. Using a quantitative labelling method, conotoxin variability was compared quantitatively, with highly expressed peptides showing a strong correlation between transcription and translation, whereas peptides expressed at lower levels showed a poor correlation. These results suggest that major transcripts are subject to stabilizing selection, while minor transcripts are subject to diversifying selection.

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46

Giribaldi, Julien, Lotten Ragnarsson, Tom Pujante, Christine Enjalbal, David Wilson, Norelle L. Daly, Richard J. Lewis, and Sebastien Dutertre. "Synthesis, Pharmacological and Structural Characterization of Novel Conopressins from Conus miliaris." Marine Drugs 18, no. 3 (March 6, 2020): 150. http://dx.doi.org/10.3390/md18030150.

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Cone snails produce a fast-acting and often paralyzing venom, largely dominated by disulfide-rich conotoxins targeting ion channels. Although disulfide-poor conopeptides are usually minor components of cone snail venoms, their ability to target key membrane receptors such as GPCRs make them highly valuable as drug lead compounds. From the venom gland transcriptome of Conus miliaris, we report here on the discovery and characterization of two conopressins, which are nonapeptide ligands of the vasopressin/oxytocin receptor family. These novel sequence variants show unusual features, including a charge inversion at the critical position 8, with an aspartate instead of a highly conserved lysine or arginine residue. Both the amidated and acid C-terminal analogues were synthesized, followed by pharmacological characterization on human and zebrafish receptors and structural investigation by NMR. Whereas conopressin-M1 showed weak and only partial agonist activity at hV1bR (amidated form only) and ZFV1a1R (both amidated and acid form), both conopressin-M2 analogues acted as full agonists at the ZFV2 receptor with low micromolar affinity. Together with the NMR structures of amidated conopressins-M1, -M2 and -G, this study provides novel structure-activity relationship information that may help in the design of more selective ligands.

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47

Saintmont, Fabrice, Guillaume Cazals, Claudia Bich та Sebastien Dutertre. "Proteomic Analysis of the Predatory Venom of Conus striatus Reveals Novel and Population-Specific κA-Conotoxin SIVC". Toxins 14, № 11 (17 листопада 2022): 799. http://dx.doi.org/10.3390/toxins14110799.

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Animal venoms are a rich source of pharmacological compounds with ecological and evolutionary significance, as well as with therapeutic and biotechnological potentials. Among the most promising venomous animals, cone snails produce potent neurotoxic venom to facilitate prey capture and defend against aggressors. Conus striatus, one of the largest piscivorous species, is widely distributed, from east African coasts to remote Polynesian Islands. In this study, we investigated potential intraspecific differences in venom composition between distinct geographical populations from Mayotte Island (Indian Ocean) and Australia (Pacific Ocean). Significant variations were noted among the most abundant components, namely the κA-conotoxins, which contain three disulfide bridges and complex glycosylations. The amino acid sequence of a novel κA-conotoxin SIVC, including its N-terminal acetylated variant, was deciphered using tandem mass spectrometry (MS/MS). In addition, the glycosylation pattern was found to be consisting of two HexNAc and four Hex for the Mayotte population, which diverge from the previously characterized two HexNAc and three Hex combinations for this species, collected elsewhere. Whereas the biological and ecological roles of these modifications remain to be investigated, population-specific glycosylation patterns provide, for the first time, a new level of intraspecific variations in cone snail venoms.

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Bulaj, G., O. Buczek, I. Goodsell, E. C. Jimenez, J. Kranski, J. S. Nielsen, J. E. Garrett, and B. M. Olivera. "Efficient oxidative folding of conotoxins and the radiation of venomous cone snails." Proceedings of the National Academy of Sciences 100, Supplement 2 (October 22, 2003): 14562–68. http://dx.doi.org/10.1073/pnas.2335845100.

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49

Puillandre, N., T. F. Duda, C. Meyer, B. M. Olivera, and P. Bouchet. "One, four or 100 genera? A new classification of the cone snails." Journal of Molluscan Studies 81, no. 1 (September 5, 2014): 1–23. http://dx.doi.org/10.1093/mollus/eyu055.

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50

Olivera, Baldomero M., Jon Seger, Martin P. Horvath, and Alexander E. Fedosov. "Prey-Capture Strategies of Fish-Hunting Cone Snails: Behavior, Neurobiology and Evolution." Brain, Behavior and Evolution 86, no. 1 (2015): 58–74. http://dx.doi.org/10.1159/000438449.

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The venomous fish-hunting cone snails (Conus) comprise eight distinct lineages evolved from ancestors that preyed on worms. In this article, we attempt to reconstruct events resulting in this shift in food resource by closely examining patterns of behavior, biochemical agents (toxins) that facilitate prey capture and the combinations of toxins present in extant species. The first sections introduce three different hunting behaviors associated with piscivory: ‘taser-and-tether', ‘net-engulfment' and ‘strike-and-stalk'. The first two fish-hunting behaviors are clearly associated with distinct groups of venom components, called cabals, which act in concert to modify the behavior of prey in a specific manner. Derived fish-hunting behavior clearly also correlates with physical features of the radular tooth, the device that injects these biochemical components. Mapping behavior, biochemical components and radular tooth features onto phylogenetic trees shows that fish-hunting behavior emerged at least twice during evolution. The system presented here may be one of the best examples where diversity in structure, physiology and molecular features were initially driven by particular pathways selected through behavior.

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