Displaying publications 1 - 20 of 33 in total

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  1. A Pseudo-nitzschia metabarcoding approach with a calibrated ITS1 reference sequence database applied in the Taiwan Strait
    Niu B, Pang J, Lundholm N, Liang C, Teng ST, Zheng Q, et al.
    Harmful Algae, 2024 Mar;133:102602.
    PMID: 38485439 DOI: 10.1016/j.hal.2024.102602
    Pseudo-nitzschia is a cosmopolitan phytoplankton genus of which some species can form blooms and produce the neurotoxin domoic acid (DA). Identification of Pseudo-nitzschia is generally based on field material or strains followed by morphological and/or molecular characterization. However, this process is time-consuming and laborious, and can not obtain a relatively complete and reliable profile of the Pseudo-nitzschia community, because species with low abundance in the field or potentially unavailable for culturing may easily be overlooked. In the present study, specific ITS primer sets were designed and evaluated using in silico matching. The primer set ITS-84F/456R involving the complete ITS1 region was found optimal. Based on matching with a Pseudo-nitzschia ITS1 reference sequence database carefully-calibrated in this study, a metabarcoding approach using annotated amplicon sequence variants (ASV) was applied in the Taiwan Strait of the East China Sea during two cruises in the spring and summer of 2019. In total, 48 Pseudo-nitzschia species/phylotypes including 36 known and 12 novel were uncovered, and verified by haplotype networks, ITS2 secondary structure comparisons and divergence analyses. Correlation analyses revealed that temperature was a key factor affecting the seasonal variation of the Pseudo-nitzschia community. This study provides an overview of the Pseudo-nitzschia community in the Taiwan Strait, with new insights into the diversity. The developed metabarcoding approach may be used elsewhere as a standard reference for accurate annotation of Pseudo-nitzschia.
    Matched MeSH terms: Neurotoxins
  2. Isolation, complete amino acid sequence and characterization of a previously unreported post-synaptic neurotoxin - AlphaN3, from the venom of Bungarus candidus
    Karsani SA, Othman I
    Biochem Biophys Res Commun, 2009 Nov 13;389(2):343-8.
    PMID: 19728988 DOI: 10.1016/j.bbrc.2009.08.145
    The Malayan krait (Bungarus candidus) is one of the medically most important snake species in Southeast Asia. The venom from this snake has been shown to posses both presynaptic and post-synaptic neurotoxins. We have isolated a previously uncharacterized post-synaptic neurotoxin - alphaN3 from the venom of B. candidus. Isolation of the toxin was achieved in three successive chromatography steps - gel filtration on a Sephadex G75 column, followed by ion exchange chromatography (Mono-S strong cationic exchanger) and a final reverse-phase chromatography step (PRO-RPC C18 column). Purified toxin alphaN3 was shown to have an apparent molecular weight of approximately 7 to 8 kDa on SDS-PAGE. The complete amino acid sequence of toxin alphaN3 was determined by Edman degradation and was found to share a high degree of homology with known post-synaptic neurotoxins (93% with alpha-bungarotoxin from Bungarus multicinctus, 50% with alpha cobratoxin from Naja kaouthia). The intravenous LD(50) of toxin alphaN3 was determined to be 0.16+/-0.09 microg/g in mice which is comparable to alpha-bungarotoxin from B. multicinctus. Experiments with isolated nerve-muscle preparations suggested that toxin alphaN3 was a post-synaptic neurotoxin that produced complete blockade of neuromuscular transmission by binding to nicotinic acetylcholine receptors.
    Matched MeSH terms: Neurotoxins/isolation & purification; Neurotoxins/pharmacology*; Neurotoxins/chemistry*
  3. A comparative study on the biological properties of venoms from juvenile and adult common tiger snake (Notechis scutatus) venoms
    Tan NH, Ponnudurai G, Mirtschin PJ
    Comp. Biochem. Physiol., B, 1993 Nov;106(3):651-4.
    PMID: 8281760
    1. The biological properties of venoms from juvenile and adult common tiger snakes (Notechis scutatus) were compared. 2. The lethality, procoagulant activity and enzymatic activities of the juvenile venom were not substantially different from those of the adult venom. 3. Electrophoretic studies, however, indicated some minor differences in the protein composition of the juvenile and adult venoms.
    Matched MeSH terms: Neurotoxins/analysis*
  4. Fulltext A pan-specific antiserum produced by a novel immunization strategy shows a high spectrum of neutralization against neurotoxic snake venoms
    Ratanabanangkoon K, Tan KY, Pruksaphon K, Klinpayom C, Gutiérrez JM, Quraishi NH, et al.
    Sci Rep, 2020 07 09;10(1):11261.
    PMID: 32647261 DOI: 10.1038/s41598-020-66657-8
    Snakebite envenomation is a neglected tropical disease of high mortality and morbidity largely due to insufficient supply of effective and affordable antivenoms. Snake antivenoms are mostly effective against the venoms used in their production. It is thus crucial that effective and affordable antivenom(s) with wide para-specificity, capable of neutralizing the venoms of a large number of snakes, be produced. Here we studied the pan-specific antiserum prepared previously by a novel immunization strategy involving the exposure of horses to a 'diverse toxin repertoire' consisting of 12 neurotoxic Asian snake toxin fractions/ venoms from six species. This antiserum was previously shown to exhibit wide para-specificity by neutralizing 11 homologous and 16 heterologous venoms from Asia and Africa. We now show that the antiserum can neutralize 9 out of 10 additional neurotoxic venoms. Altogether, 36 snake venoms belonging to 10 genera from 4 continents were neutralized by the antiserum. Toxin profiles previously generated using proteomic techniques of these 36 venoms identified α-neurotoxins, β-neurotoxins, and cytotoxins as predominant toxins presumably neutralized by the antiserum. The bases for the wide para-specificity of the antiserum are discussed. These findings indicate that it is feasible to generate antivenoms of wide para-specificity against elapid neurotoxic venoms from different regions in the world and raises the possibility of a universal neurotoxic antivenom. This should reduce the mortality resulting from neurotoxic snakebite envenomation.
    Matched MeSH terms: Neurotoxins/chemistry*
  5. Fulltext An in vitro α-neurotoxin-nAChR binding assay correlates with lethality and in vivo neutralization of a large number of elapid neurotoxic snake venoms from four continents
    Pruksaphon K, Tan KY, Tan CH, Simsiriwong P, Gutiérrez JM, Ratanabanangkoon K
    PLoS Negl Trop Dis, 2020 Aug;14(8):e0008581.
    PMID: 32857757 DOI: 10.1371/journal.pntd.0008581
    The aim of this study was to develop an in vitro assay for use in place of in vivo assays of snake venom lethality and antivenom neutralizing potency. A novel in vitro assay has been developed based on the binding of post-synaptically acting α-neurotoxins to nicotinic acetylcholine receptor (nAChR), and the ability of antivenoms to prevent this binding. The assay gave high correlation in previous studies with the in vivo murine lethality tests (Median Lethal Dose, LD50), and the neutralization of lethality assays (Median Effective Dose, ED50) by antisera against Naja kaouthia, Naja naja and Bungarus candidus venoms. Here we show that, for the neurotoxic venoms of 20 elapid snake species from eight genera and four continents, the in vitro median inhibitory concentrations (IC50s) for α-neurotoxin binding to purified nAChR correlated well with the in vivo LD50s of the venoms (R2 = 0.8526, p < 0.001). Furthermore, using this assay, the in vitro ED50s of a horse pan-specific antiserum against these venoms correlated significantly with the corresponding in vivo murine ED50s, with R2 = 0.6896 (p < 0.01). In the case of four elapid venoms devoid or having a very low concentration of α-neurotoxins, no inhibition of nAChR binding was observed. Within the philosophy of 3Rs (Replacement, Reduction and Refinement) in animal testing, the in vitro α-neurotoxin-nAChR binding assay can effectively substitute the mouse lethality test for toxicity and antivenom potency evaluation for neurotoxic venoms in which α-neurotoxins predominate. This will greatly reduce the number of mice used in toxicological research and antivenom production laboratories. The simpler, faster, cheaper and less variable in vitro assay should also expedite the development of pan-specific antivenoms against various medically important snakes in many parts of the world.
    Matched MeSH terms: Neurotoxins/immunology; Neurotoxins/toxicity; Neurotoxins/chemistry*
  6. Unlocking the secrets of banded coral snake (Calliophis intestinalis, Malaysia): A venom with proteome novelty, low toxicity and distinct antigenicity
    Tan KY, Liew JL, Tan NH, Quah ESH, Ismail AK, Tan CH
    J Proteomics, 2019 02 10;192:246-257.
    PMID: 30243938 DOI: 10.1016/j.jprot.2018.09.006
    The Asiatic coral snakes are basal in the phylogeny of coral snakes. Although envenoming by the Asiatic coral snakes is rarely fatal, little is known about their venom properties and variability from the American coral snakes. Integrating reverse-phase high performance liquid chromatography and nano-liquid chromatography-tandem mass spectrometry, we showed that the venom proteome of the Malaysian banded or striped coral snake (Calliophis intestinalis) was composed of mainly phospholipases A2 (PLA2, 43.4%) and three-finger toxins (3FTx, 20.1%). Within 3FTx, the cytotoxins or cardiotoxins (CTX) dominated while the neurotoxins' content was much lower. Its subproteomic details contrasted with the 3FTx profile of most Micrurus sp., illustrating a unique dichotomy of venom phenotype between the Old and the New World coral snakes. Calliophis intestinalis venom proteome was correlated with measured enzymatic activities, and in vivo it was myotoxic but non-lethal to mice, frogs and geckos at high doses (5-10 μg/g). The venom contains species-specific toxins with distinct sequences and antigenicity, and the antibodies raised against PLA2 and CTX of other elapids showed poor binding toward its venom antigens. The unique venom proteome of C. intestinalis unveiled a repertoire of novel toxins, and the toxicity test supported the need for post-bite monitoring of myotoxic complication. SIGNIFICANCE: Malaysian banded or striped coral snake (Calliophis intestinalis) has a cytotoxin (CTX)-predominating venom proteome, a characteristic shared by its congener, the Malayan blue coral snake (Calliophis bivirgata). With little neurotoxins (NTX), it illustrates a CTX/NTX dichotomy of venom phenotype between the Old World and the New World coral snakes. The low toxicity of the venom imply that C. intestinalis bite envenoming can be managed via symptomatic relief of the mild to moderate pain with appropriate analgesia. Systemically, the serum creatine kinase level of patients should be monitored serially for potential complication of myotoxicity. The distinct antigenicity of the venom proteins implies that the empirical use of heterologous antivenom is mostly inappropriate and not recommended.
    Matched MeSH terms: Neurotoxins/genetics; Neurotoxins/metabolism*
  7. Fulltext De Novo Venom-Gland Transcriptomics of Spine-Bellied Sea Snake (Hydrophis curtus) from Penang, Malaysia-Next-Generation Sequencing, Functional Annotation and Toxinological Correlation
    Tan CH, Tan KY
    Toxins (Basel), 2021 02 09;13(2).
    PMID: 33572266 DOI: 10.3390/toxins13020127
    Envenomation resulted from sea snake bite is a highly lethal health hazard in Southeast Asia. Although commonly caused by sea snakes of Hydrophiinae, each species is evolutionarily distinct and thus, unveiling the toxin gene diversity within individual species is important. Applying next-generation sequencing, this study investigated the venom-gland transcriptome of Hydrophis curtus (spine-bellied sea snake) from Penang, West Malaysia. The transcriptome was de novo assembled, followed by gene annotation and sequence analyses. Transcripts with toxin annotation were only 96 in number but highly expressed, constituting 48.18% of total FPKM in the overall transcriptome. Of the 21 toxin families, three-finger toxins (3FTX) were the most abundantly expressed and functionally diverse, followed by phospholipases A2. Lh_FTX001 (short neurotoxin) and Lh_FTX013 (long neurotoxin) were the most dominant 3FTXs expressed, consistent with the pathophysiology of envenomation. Lh_FTX001 and Lh_FTX013 were variable in amino acid compositions and predicted epitopes, while Lh_FTX001 showed high sequence similarity with the short neurotoxin from Hydrophis schistosus, supporting cross-neutralization effect of Sea Snake Antivenom. Other toxins of low gene expression, for example, snake venom metalloproteinases and L-amino acid oxidases not commonly studied in sea snake venom were also identified, enriching the knowledgebase of sea snake toxins for future study.
    Matched MeSH terms: Neurotoxins/genetics*; Neurotoxins/immunology; Neurotoxins/metabolism; Neurotoxins/toxicity
  8. Comparison of the neurotoxic and myotoxic effects of two Moroccan scorpion venoms and their neutralization by experimental polyclonal antivenom
    Oukkache N, Ahmad Rusmili MR, Othman I, Ghalim N, Chgoury F, Boussadda L, et al.
    Life Sci, 2015 Mar 1;124:1-7.
    PMID: 25623852 DOI: 10.1016/j.lfs.2014.12.031
    Scorpion venoms contain complex mixtures of molecules, including peptides. These peptides specifically bind to various targets, in particular ion channels. Toxins modulating Na(+), K(+), Ca(2+) and Cl(-) currents were described from venoms. The Androctonus and Buthus geni of scorpions are widely distributed in Morocco. Their stings can cause pain, inflammation, necrosis, muscle paralysis and death. The myotoxicity is predominantly associated with neurotoxic effects and is a cause of mortality and morbidity. In this study, pharmacological effects of venoms were investigated in vitro on neuromuscular transmission.
    Matched MeSH terms: Neurotoxins/isolation & purification; Neurotoxins/toxicity*
  9. Isolation and characterization of a presynaptic neurotoxin, P-elapitoxin-Bf1a from Malaysian Bungarus fasciatus venom
    Rusmili MR, Yee TT, Mustafa MR, Hodgson WC, Othman I
    Biochem Pharmacol, 2014 Oct 1;91(3):409-16.
    PMID: 25064255 DOI: 10.1016/j.bcp.2014.07.001
    Presynaptic neurotoxins are one of the major components in Bungarus venom. Unlike other Bungarus species that have been studied, β-bungarotoxin has never been isolated from Bungarus fasciatus venom. It was hypothesized that the absence of β-bungarotoxin in this species was due to divergence during evolution prior to evolution of β-bungarotoxin. In this study, we have isolated a β-bungarotoxin isoform we named P-elapitoxin-Bf1a by using gel filtration, cation-exchange and reverse-phase chromatography from Malaysian B. fasciatus venom. The toxin consists of two heterogeneous subunits, subunit A and subunit B. LCMS/MS data showed that subunit A was homologous to acidic phospholipase A2 subunit A3 from Bungarus candidus and B. multicinctus venoms, whereas subunit B was homologous with subunit B1 from B. fasciatus venom that was previously detected by cDNA cloning. The toxin showed concentration- and time-dependent reduction of indirect-twitches without affecting contractile responses to ACh, CCh or KCl at the end of experiment in the chick biventer preparation. Toxin modification with 4-BPB inhibited the neurotoxic effect suggesting the importance of His-48. Tissue pre-incubation with monovalent B. fasciatus (BFAV) or neuro-polyvalent antivenom (NPV), at the recommended titer, was unable to inhibit the twitch reduction induced by the toxin. This study indicates that Malaysian B. fasciatus venom has a unique β-bungarotoxin isoform which was not neutralized by antivenoms. This suggests that there might be other presynaptic neurotoxins present in the venom and there is a variation in the enzymatic neurotoxin composition in venoms from different localities.
    Matched MeSH terms: Neurotoxins/isolation & purification*; Neurotoxins/pharmacology*
  10. Phylogenetic relationships, morphological variation, and toxin patterns in the Alexandrium ostenfeldii (Dinophyceae) complex: implications for species boundaries and identities
    Kremp A, Tahvanainen P, Litaker W, Krock B, Suikkanen S, Leaw CP, et al.
    J Phycol, 2014 Feb;50(1):81-100.
    PMID: 26988010 DOI: 10.1111/jpy.12134
    Alexandrium ostenfeldii (Paulsen) Balech and Tangen and A. peruvianum (Balech and B.R. Mendiola) Balech and Tangen are morphologically closely related dinoflagellates known to produce potent neurotoxins. Together with Gonyaulax dimorpha Biecheler, they constitute the A. ostenfeldii species complex. Due to the subtle differences in the morphological characters used to differentiate these species, unambiguous species identification has proven problematic. To better understand the species boundaries within the A. ostenfeldii complex we compared rDNA data, morphometric characters and toxin profiles of multiple cultured isolates from different geographic regions. Phylogenetic analysis of rDNA sequences from cultures characterized as A. ostenfeldii or A. peruvianum formed a monophyletic clade consisting of six distinct groups. Each group examined contained strains morphologically identified as either A. ostenfeldii or A. peruvianum. Though key morphological characters were generally found to be highly variable and not consistently distributed, selected plate features and toxin profiles differed significantly among phylogenetic clusters. Additional sequence analyses revealed a lack of compensatory base changes in ITS2 rRNA structure, low to intermediate ITS/5.8S uncorrected genetic distances, and evidence of reticulation. Together these data (criteria currently used for species delineation in dinoflagellates) imply that the A. ostenfeldii complex should be regarded a single genetically structured species until more material and alternative criteria for species delimitation are available. Consequently, we propose that A. peruvianum is a heterotypic synonym of A. ostenfeldii and this taxon name should be discontinued.
    Matched MeSH terms: Neurotoxins
  11. Isolation and characterization of α-elapitoxin-Bf1b, a postsynaptic neurotoxin from Malaysian Bungarus fasciatus venom
    Rusmili MR, Tee TY, Mustafa MR, Othman I, Hodgson WC
    Biochem Pharmacol, 2014 Mar 15;88(2):229-36.
    PMID: 24440452 DOI: 10.1016/j.bcp.2014.01.004
    Bungarus fasciatus is one of three species of krait found in Malaysia. Envenoming by B. fasciatus results in neurotoxicity due to the presence of presynaptic and postsynaptic neurotoxins. Antivenom, either monovalent or polyvalent, is the treatment of choice in systemically envenomed patients. In this study, we have isolated a postsynaptic neurotoxin which we named α-elapitoxin-Bf1b. This toxin has an approximate molecular weight of 6.9 kDa, with LCMS/MS data showing that it is highly homologous with Neurotoxin 3FTx-RI, a toxin identified in the Bungarus fasciatus venom gland transcriptome. α-Elapitoxin-Bf1b also shared similarity with short-chain neurotoxins from Laticauda colubrina and Pseudechis australis. α-Elapitoxin-Bf1b produced concentration- and time-dependent neurotoxicity in the indirectly-stimulated chick biventer cervicis muscle preparation, an effect partially reversible by repetitive washing of the preparation. The pA2 value for α-elapitoxin-Bf1b of 9.17 ± 0.64, determined by examining the effects of the toxin on cumulative carbacol concentration-response curves, indicated that the toxin is more potent than tubocurarine and α-bungarotoxin. Pre-incubation of Bungarus fasciatus monovalent and neuro polyvalent antivenom failed to prevent the neurotoxic effects of α-elapitoxin-Bf1b in the chick biventer cervicis muscle preparation. In conclusion, the isolation of a postsynaptic neurotoxin that cannot be neutralized by either monovalent and polyvalent antivenoms may indicate the presence of isoforms of postsynaptic neurotoxins in Malaysian B. fasciatus venom.
    Matched MeSH terms: Neurotoxins/genetics*; Neurotoxins/isolation & purification*; Neurotoxins/toxicity
  12. Revisiting Notechis scutatus venom: on shotgun proteomics and neutralization by the "bivalent" Sea Snake Antivenom
    Tan CH, Tan KY, Tan NH
    J Proteomics, 2016 07 20;144:33-8.
    PMID: 27282922 DOI: 10.1016/j.jprot.2016.06.004
    Recent advances in proteomics enable deep profiling of the compositional details of snake venoms for improved understanding on envenomation pathophysiology and immunological neutralization. In this study, the venom of Australian tiger snake (Notechis scutatus) was trypsin-digested in solution and subjected to nano-ESI-LCMS/MS. Applying a relative quantitative proteomic approach, the findings revealed a proteome comprising 42 toxin subtypes clustered into 12 protein families. Phospholipases A2 constitute the most abundant toxins (74.5% of total venom proteins) followed by Kunitz serine protease inhibitors (6.9%), snake venom serine proteases (5.9%), alpha-neurotoxins (5.6%) and several toxins of lower abundance. The proteome correlates with N. scutatus envenoming effects including pre-synaptic and post-synaptic neurotoxicity and consumptive coagulopathy. The venom is highly lethal in mice (intravenous median lethal dose=0.09μg/g). BioCSL Sea Snake Antivenom, raised against the venoms of beaked sea snake (Hydrophis schistosus) and N. scutatus (added for enhanced immunogenicity), neutralized the lethal effect of N. scutatus venom (potency=2.95mg/ml) much more effectively than the targeted H.schistosus venom (potency=0.48mg/ml). The combined venom immunogen may have improved the neutralization against phospholipases A2 which are abundant in both venoms, but not short-neurotoxins which are predominant only in H. schistosus venom.

    SIGNIFICANCE: A shotgun proteomic approach adopted in this study revealed the compositional details of the venom of common tiger snake from Australia, Notechis scutatus. The proteomic findings provided additional information on the relative abundances of toxins and the detection of proteins of minor expression unreported previously. The potent lethal effect of the venom was neutralized by bioCSL Sea Snake Antivenom, an anticipated finding due to the fact that the Sea Snake Antivenom is actually bivalent in nature, being raised against a mix of venoms of the beaked sea snake (Hydrophis schistosus) and N. scutatus. However, it is surprising to note that bioCSL Sea Snake Antivenom neutralized N. scutatus venom much more effectively compared to the targeted sea snake venom by a marked difference in potency of approximately 6-fold. This phenomenon may be explained by the main difference in the proteomes of the two venoms, where H. schistosus venom is dominated by short-neurotoxins in high abundance - this is a poorly immunogenic toxin group that has been increasingly recognized in the venoms of a few cobras. Further investigations should be directed toward strategies to improve the neutralization of short-neurotoxins, in line with the envisioned production of an effective pan-regional elapid antivenom.

    Matched MeSH terms: Neurotoxins/immunology
  13. Fulltext In-vitro neurotoxicity of two Malaysian krait species (Bungarus candidus and Bungarus fasciatus) venoms: neutralization by monovalent and polyvalent antivenoms from Thailand
    Rusmili MR, Yee TT, Mustafa MR, Othman I, Hodgson WC
    Toxins (Basel), 2014 Mar;6(3):1036-48.
    PMID: 24625762 DOI: 10.3390/toxins6031036
    Bungarus candidus and Bungarus fasciatus are two species of krait found in Southeast Asia. Envenoming by these snakes is often characterized by neurotoxicity and, without treatment, causes considerable morbidity and mortality. In this study, the in vitro neurotoxicity of each species, and the effectiveness of two monovalent antivenoms and a polyvalent antivenom, against the neurotoxic effects of the venoms, were examined in a skeletal muscle preparation. Both venoms caused concentration-dependent inhibition of indirect twitches, and attenuated responses to exogenous nicotinic receptor agonists, in the chick biventer preparation, with B. candidus venom being more potent than B. fasciatus venom. SDS-PAGE and western blot analysis indicated different profiles between the venoms. Despite these differences, most proteins bands were recognized by all three antivenoms. Antivenom, added prior to the venoms, attenuated the neurotoxic effect of the venoms. Interestingly, the respective monovalent antivenoms did not neutralize the effects of the venom from the other Bungarus species indicating a relative absence of cross-neutralization. Addition of a high concentration of polyvalent antivenom, at the t90 time point after addition of venom, partially reversed the neurotoxicity of B. fasciatus venom but not B. candidus venom. The monovalent antivenoms had no significant effect when added at the t90 time point. This study showed that B. candidus and B. fasciatus venoms display marked in vitro neurotoxicity in the chick biventer preparation and administration of antivenoms at high dose is necessary to prevent or reverse neurotoxicity.
    Matched MeSH terms: Neurotoxins/toxicity*
  14. Fulltext Lithium neurotoxicity
    Suraya Y, Yoong KY
    Med J Malaysia, 2001 Sep;56(3):378-81.
    PMID: 11732087
    Inspite of the advent of newer antimanic drugs, lithium carbonate remains widely used in the treatment and prevention of manic-depressive illness. However care has to be exercised due to its low therapeutic index. The central nervous system and renal system are predominantly affected in acute lithium intoxication and is potentially lethal. The more common side effect involves the central nervous system. It occurs early and is preventable. We describe three cases of lithium toxicity admitted to Johor Bahru Hospital, with emphasis on its neurological preponderance.
    Matched MeSH terms: Neurotoxins*
  15. Extremely low nerve growth facior (NGF) activity of sea snake (Hydrophiidae) venoms
    Mariam K, Tu AT
    J Nat Toxins, 2002 Dec;11(4):393-8.
    PMID: 12503884
    Sea snake venoms contain less protein than those of land snakes (Toom et al., 1969). Sea snake venoms lack arginine ester hydrolyzing activity, whereas those of Crotalidae and Viperidae have such activity (Tu et al., 1966). Sea snakes live in salty water, and their venoms may be different from those of land snakes. Because of the difficulty in obtaining sea snake venoms, information about sea snake venoms is quite incomplete. NGF is commonly present in the venoms of land snakes such as Elapidae, Viperidae, and Crotalidae (Cohen and Levi-Montalcini, 1956; Lipps, 2002). It is therefore of interest to investigate the presence or absence of NGF in sea snake venoms. In order to investigate the presence or absence of NGF, five sea snake venoms were selected. Lapemis hardwickii (Hardwick's sea snake) and Acalyptophis peronii venom were obtained from the Gulf of Thailand. Hydrophis cyanocinctus (common sea snake) and Enhydrina schistosa (beaked sea snake) venom were obtained from the Strait of Malacca. Laticauda semifasciata (broad band blue sea snake) venom was also examined and the venom was obtained from Gato Island in the Philippines.
    Matched MeSH terms: Neurotoxins/biosynthesis
  16. Fulltext A neurotoxin that specifically targets Anopheles mosquitoes
    Contreras E, Masuyer G, Qureshi N, Chawla S, Dhillon HS, Lee HL, et al.
    Nat Commun, 2019 06 28;10(1):2869.
    PMID: 31253776 DOI: 10.1038/s41467-019-10732-w
    Clostridial neurotoxins, including tetanus and botulinum neurotoxins, generally target vertebrates. We show here that this family of toxins has a much broader host spectrum, by identifying PMP1, a clostridial-like neurotoxin that selectively targets anopheline mosquitoes. Isolation of PMP1 from Paraclostridium bifermentans strains collected in anopheline endemic areas on two continents indicates it is widely distributed. The toxin likely evolved from an ancestral form that targets the nervous system of similar organisms, using a common mechanism that disrupts SNARE-mediated exocytosis. It cleaves the mosquito syntaxin and employs a unique receptor recognition strategy. Our research has an important impact on the study of the evolution of clostridial neurotoxins and provides the basis for the use of P. bifermentans strains and PMP1 as innovative, environmentally friendly approaches to reduce malaria through anopheline control.
    Matched MeSH terms: Neurotoxins/pharmacology*
  17. The in vitro neuromuscular activity of Indo-Pacific sea-snake venoms: efficacy of two commercially available antivenoms
    Chetty N, Du A, Hodgson WC, Winkel K, Fry BG
    Toxicon, 2004 Aug;44(2):193-200.
    PMID: 15246769
    We examined the neurotoxicity of the following sea snake venoms: Enhydrina schistosa (geographical variants from Weipa and Malaysia), Lapemis curtus (Weipa and Malaysia), Laticauda colubrina, Aipysurus laevis, Aipysurus fuscus and Aipysurus foliosquamatus. Venom from a terrestrial snake, Notechis scutatus (tiger snake), was used as a reference. All venoms (1 and 3 microg/ml) abolished indirect twitches of the chick biventer cervicis muscle and significantly inhibited responses to ACh (1 mM) and CCh (20 microM), but not KCl (40 mM), indicating the presence of post-synaptic toxins. Prior administration (10 min) of CSL sea snake antivenom (1 unit/ml) attenuated the twitch blockade produced by N. scutatus venom and all sea snake venoms (1 microg/ml). Prior administration (10 min) of CSL tiger snake antivenom (1 unit/ml) attenuated the twitch blockade of all venoms except those produced by E. schistosa (Malaysia and Weipa) and A. foliosquamatus. Administration of CSL sea snake antivenom (1 unit/ml) at t90 (i.e. time at which 90% inhibition of initial twitch height occurred) reversed the inhibition of twitches (20-50%) produced by the sea snake venoms (1 microg/ml) but not by N. scutatus venom (1 microg/ml). CSL tiger snake antivenom (1 unit/ml) administered at t90 produced only minor reversal (i.e. 15-25%) of the twitch blockade caused by L. curtus (Weipa), A. foliosquamatus, L. colubrina and A. laevis venoms (1 microg/ml). Differences in the rate of reversal of the neurotoxicity produced by the two geographical variants of E. schistosa venom, after addition of CSL sea snake antivenom, indicate possible differences in venom components. This study shows that sea snake venoms contain potent post-synaptic activity that, despite the significant genetic distances between the lineages, can be neutralised with CSL sea snake antivenom. However, the effects of CSL tiger snake antivenom are more variable.
    Matched MeSH terms: Neurotoxins/toxicity*
  18. Venom proteome of the yellow-lipped sea krait, Laticauda colubrina from Bali: Insights into subvenomic diversity, venom antigenicity and cross-neutralization by antivenom
    Tan CH, Wong KY, Tan KY, Tan NH
    J Proteomics, 2017 08 23;166:48-58.
    PMID: 28688916 DOI: 10.1016/j.jprot.2017.07.002
    The venom proteome of Laticauda colubrina (Bali, Indonesia) was elucidated by nano-ESI-LCMS/MS of the venom reverse-phase HPLC fractions. Altogether 31 distinct forms of proteins were identified and clustered into three toxin families: three-finger toxin (3FTX, 66.12% of total venom proteins), phospholipase A2 (PLA2, 33.26%) and cysteine-rich secretory protein (CRiSP, 0.05%). The 3FTX were α-neurotoxins (five long neurotoxins, LNTX, 48.87%; two short neurotoxins, SNTX, 16.94%) and a trace amount of two cytotoxins (CTX, 0.31%). PLA2 were present with a large diversity of homologues (≥20 forms), however none was annotated to the lethal proteoform reported previously. The venom is highly lethal in mice (LD50=0.10μg/g) and this is driven primarily by the SNTX and LNTX (LD50=0.05-0.13μg/g), since the PLA2 proteins were non-lethal up to 2μg/g (20-time the venom LD50). The SNTX and LNTX were effectively cross-neutralized by the heterologous Sea Snake Antivenom (SSAV, Australian product) (potency=0.27mg toxin per ml antivenom, and 0.40mg/ml, respectively), corroborating the cross-neutralization of the whole venom (potency=1.09mg/ml) and its antigenic immunoreactivity toward SSAV. Furthermore, compared with earlier studies, the present work reveals geographical variation of venom composition for L. colubrina which may have implication for the evolution and conservation of the species.

    BIOLOGICAL SIGNIFICANCE: Laticauda colubrina (yellow-lipped sea krait) is a widely distributed, semi-aquatic venomous snake species. The venom proteome at the level of protein family is unsophisticated and consistent with its restricted prey selection. Nonetheless, the subproteomic findings revealed geographical variability of the venom for this widely distributed species. In contrast to two previous reports, the results for the Balinese L. colubrina venom showed that LNTX Neurotoxin a and Neurotoxin b were co-existent while the PLA2 lethal subtype (PLA-II) was undetected by means of LCMS/MS and by in vivo assay. This is an observable trait of L. colubrina considered divergent from specimens previously studied for the Philippines and the Solomon Islands. The stark geographical variation might be reflective of trophic adaptation following evolutionary arms race between the snake and the prey (eels) in different localities. The preferred trait would likely propagate and remain significant within the geographical population, since the strong behaviour of site fidelity in the species would have minimized gene flow between distant populations. Meanwhile, the in vivo neutralization study verified that the efficacy of the heterologous Sea Snake Antivenom (Australian product) is attributable to the cross-neutralization of SNTX and LNTX, two principal lethal toxins that made up the bulk of L. colubrina venom proteins. The findings also implied that L. colubrina, though could be evolutionarily more related to the terrestrial elapids, has evolved a much streamlined, neurotoxin- and PLA2-predominated venom arsenal, with major antigenicity shared among the true sea snakes and the Australo-Papuan elapids. The findings enrich our current understanding of the complexity of L. colubrina venom and the neutralizing spectrum of antivenom against the principal toxins from this unique elapid lineage.

    Matched MeSH terms: Neurotoxins/analysis
  19. Fulltext Biosynthesis of Saxitoxin in Marine Dinoflagellates: An Omics Perspective
    Akbar MA, Mohd Yusof NY, Tahir NI, Ahmad A, Usup G, Sahrani FK, et al.
    Mar Drugs, 2020 Feb 05;18(2).
    PMID: 32033403 DOI: 10.3390/md18020103
    Saxitoxin is an alkaloid neurotoxin originally isolated from the clam Saxidomus giganteus in 1957. This group of neurotoxins is produced by several species of freshwater cyanobacteria and marine dinoflagellates. The saxitoxin biosynthesis pathway was described for the first time in the 1980s and, since then, it was studied in more than seven cyanobacterial genera, comprising 26 genes that form a cluster ranging from 25.7 kb to 35 kb in sequence length. Due to the complexity of the genomic landscape, saxitoxin biosynthesis in dinoflagellates remains unknown. In order to reveal and understand the dynamics of the activity in such impressive unicellular organisms with a complex genome, a strategy that can carefully engage them in a systems view is necessary. Advances in omics technology (the collective tools of biological sciences) facilitated high-throughput studies of the genome, transcriptome, proteome, and metabolome of dinoflagellates. The omics approach was utilized to address saxitoxin-producing dinoflagellates in response to environmental stresses to improve understanding of dinoflagellates gene-environment interactions. Therefore, in this review, the progress in understanding dinoflagellate saxitoxin biosynthesis using an omics approach is emphasized. Further potential applications of metabolomics and genomics to unravel novel insights into saxitoxin biosynthesis in dinoflagellates are also reviewed.
    Matched MeSH terms: Neurotoxins/metabolism
  20. Neurotoxicity in Sri Lankan Russell's Viper (Daboia russelii) Envenoming is Primarily due to U1-viperitoxin-Dr1a, a Pre-Synaptic Neurotoxin
    Silva A, Kuruppu S, Othman I, Goode RJ, Hodgson WC, Isbister GK
    Neurotox Res, 2017 01;31(1):11-19.
    PMID: 27401825 DOI: 10.1007/s12640-016-9650-4
    Russell's vipers are snakes of major medical importance in Asia. Russell's viper (Daboia russelii) envenoming in Sri Lanka and South India leads to a unique, mild neuromuscular paralysis, not seen in other parts of the world where the snake is found. This study aimed to identify and pharmacologically characterise the major neurotoxic components of Sri Lankan Russell's viper venom. Venom was fractionated using size exclusion chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC). In vitro neurotoxicities of the venoms, fractions and isolated toxins were measured using chick biventer and rat hemidiaphragm preparations. A phospholipase A2 (PLA2) toxin, U1-viperitoxin-Dr1a (13.6 kDa), which constitutes 19.2 % of the crude venom, was isolated and purified using HPLC. U1-viperitoxin-Dr1a produced concentration-dependent in vitro neurotoxicity abolishing indirect twitches in the chick biventer nerve-muscle preparation, with a t 90 of 55 ± 7 min only at 1 μM. The toxin did not abolish responses to acetylcholine and carbachol indicating pre-synaptic neurotoxicity. Venom, in the absence of U1-viperitoxin-Dr1a, did not induce in vitro neurotoxicity. Indian polyvalent antivenom, at the recommended concentration, only partially prevented the neurotoxic effects of U1-viperitoxin-Dr1a. Liquid chromatography mass spectrometry analysis confirmed that U1-viperitoxin-Dr1a was the basic S-type PLA2 toxin previously identified from this venom (NCBI-GI: 298351762; SwissProt: P86368). The present study demonstrates that neurotoxicity following Sri Lankan Russell's viper envenoming is primarily due to the pre-synaptic neurotoxin U1-viperitoxin-Dr1a. Mild neurotoxicity observed in severely envenomed Sri Lankan Russell's viper bites is most likely due to the low potency of U1-viperitoxin-Dr1a, despite its high relative abundance in the venom.
    Matched MeSH terms: Neurotoxins/genetics; Neurotoxins/isolation & purification; Neurotoxins/toxicity*; Neurotoxins/chemistry
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