Distinct activities of novel neurotoxins from Australian venomous snakes for nicotinic acetylcholine receptors

Abstract

Envenomation from Australian elapid snakes results in a myriad of neurological effects due to post-synaptic neurotoxins that bind and inhibit nicotinic acetylcholine receptors (nAChRs) of neurons and muscle fibres. However, despite the significant physiological effects of these toxins, they have remained largely undercharacterised at the molecular level. This study describes the identification and comparative analysis of multiple neurotoxin isoforms from ten Australian snakes, including functional characterisation of two of these isoforms, Os SNTX-1 from Oxyuranus scutellatus and the more potent Pt LNTX-1 from Pseudonaja textilis. Electrophysiological recordings from adrenal chromaffin cells demonstrate that both neurotoxins act as competitive antagonists of nAChRs in a concentration-dependent manner. Their effects upon spontaneous and nerve-evoked membrane responses at the amphibian neuromuscular junction provide further evidence that both toxins bind muscle nAChRs in an irreversible manner. This study represents one of the most comprehensive descriptions to date of the sequences and activity of individual Australian elapid neurotoxins.

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

“…Named ohanin, it became the first snake venom vespryn. Additional vespryns have subsequently been sequenced from various elapids [239] and crotalids [2,10,240,241], and from the viperid, Echis coloratus [242]. Crotalid vespryns are 28–32 residues longer at their N-termini than the elapid toxins.…”

Common evolution of waprin and kunitz-like toxin families in Australian venomous snakes

“…Anti-bacterial effects of omwaprin-b were further examined using the gram positive bacterial strains Staphylococcus aureus, Staphylococcus epidermis and Streptococcus epidermis in addition to the gram negative strains Escherichia coli and Pseudomonas aeruginosa according to the protocols described by Nair et al [17]. Potential neurotoxic effects of omwaprin-b were also examined via an ex vivo amphibian electrophysiological assay, testing inhibitory effects on end-plate potentials (EPPs) and minature EPPs at the toad neuromuscular-junction as previously described [29].…”

Venomics of the Australian eastern brown snake ( Pseudonaja textilis ): Detection of new venom proteins and splicing variants

“…The molecular accelerated evolution, classification and nomenclature of these toxins are subject to debate Sunagar et al, 2013). Although a huge diversity of genes and transcripts have been described (Gong et al, 1999;Jackson et al, 2013;St Pierre et al, 2007b;Tyler et al, 1987), the usual simplified short-chain neurotoxin (SNTx) or long-chain neurotoxin (LNTx) classification is used here (Hegde et al, 2009).…”

“…The previously described "LNTx-1" (St Pierre et al, 2007b) and an isoform were identified in isogroup 23. The isogroup 83 encodes for "Pseudonajatoxin b homologue" (Gong et al, 2001) and isotig 1328 is a new LNTx transcript, named here "LNTx-2", with 93% translation similarity to a Pseudonaja modesta LNTx (Accession: R4G319_9SAUR) , 85% to a-neurotoxin "LNTx 20" from Drysdalia coronoides (Accession: 3FL20_DRYCN) (Chatrath et al, 2011) and only 78% similar to "Pseudonajatoxin b homologue".…”

“…Its venom has been described as containing toxins that induce defibrination coagulopathy, renal failure and microangiopathic hemolytic anemia (White, 2009). Although neurotoxicity is considered to be rare (Barber et al, 2012;White, 2009), a potent presynaptic neurotoxin named textilotoxin has been described (Aquilina, 2009;Pearson et al, 1993) as well as short and long three-finger postsynaptic toxins (3FTx) (Gong et al, 2001(Gong et al, , 2000St Pierre et al, 2007b). The low P. textilis venom yield associated to low neurotoxins concentrations (Barber et al, 2012) and the usual low venom/victim weight ratio (Mirtschin et al, 1998) can be considered as an explanation for this apparent paradox, although specificity of the toxin towards nerve terminals in a specific prey type should not be discounted as a possible explanation.…”