Venom Proteome of Spine-Bellied Sea Snake (Hydrophis curtus) from Penang, Malaysia: Toxicity Correlation, Immunoprofiling and Cross-Neutralization by Sea Snake Antivenom

Tan, Choo Hock; Tan, Kae Yi; Ng, Tzu Shan; Sim, Si Mui; Tan, Nget Hong

doi:10.3390/toxins11010003

Cited by 41 publications

(47 citation statements)

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“…Notably, the composition and abundance of H. curtus toxins identi ed in the present study apparently differed from those in previous investigations either at the mRNA or protein level [6,8,19]. For example, the toxin transcripts of the H. curtus venom gland was shown to be mainly comprised of 3-FTx, PLA 2 , CRISP, and PDGF families using Sanger sequencing, with the rst three families accounting for 55.5% of the total venom-gland transcriptome and the 3-FTx family expressed more abundantly than PLA 2 at a ratio of 4.4:1 [19].…”

Section: Discussioncontrasting

confidence: 99%

“…When compared with previously investigated H. curtus venoms from Australia and Malaysia [6,8], the venom from the South China Sea population evaluated in the presented study diverged signi cantly with regard to the relative abundance of predominant toxins at the protein level. The South China Sea population exhibited the lowest abundance of PLA 2 but the highest abundance of 3-FTx, especially SNX, which was approximately 4-and 1.45-fold higher than those from Australia and Malaysia, respectively.…”

Section: Discussionmentioning

confidence: 69%

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Venom-gland Transcriptomic, Venomic, and Antivenomic Profiles of the Spine-bellied Sea Snake (Hydrophis curtus) from the South China Sea

Zhao

Wen

et al. 2020

Preprint

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Background: A comprehensive evaluation of the -omic profiles of venom is important for understanding the potential function and evolution of snake venom. Here, we conducted an integrated multi-omics-analysis to unveil the venom-transcriptomic and venomic profiles in a same group of spine-bellied sea snakes (Hydrophis curtus) from the South China Sea, where the snake is a widespread species and might generate regionally-specific venom potentially harmful to human activities. The capacity of two heterologous antivenoms to immunocapture the H. curtus venom was determined for an in-depth evaluation of their rationality in treatment of H. curtus envenomation. In addition, a phylogenetic analysis by maximum likelihood was used to detect the adaptive molecular evolution of full-length toxin-coding unigenes.Results: A total of 90,909,384 pairs of clean reads were generated via Illumina sequencing from a pooled cDNA library of six specimens, and yielding 148,121 unigenes through de novo assembly. Sequence similarity searching harvested 63,845 valid annotations, including 63,789 non-toxin-coding and 56 toxin-coding unigenes belonging to 22 protein families. Three protein families, three-finger toxins (3-FTx), phospholipase A2 (PLA2), and cysteine-rich secretory protein, were detected in the venom proteome. 3-FTx (27.15% in the transcriptome/41.94% in the proteome) and PLA2 (59.71%/49.36%) were identified as the most abundant families in the venom-gland transcriptome and venom proteome. In addition, 24 unigenes from 11 protein families were shown to have experienced positive selection in their evolutionary history, whereas four were relatively conserved throughout evolution. Commercial Naja atra antivenom exhibited a stronger capacity than Bungarus multicinctus antivenom to immunocapture H. curtus venom components, especially short neurotoxins, with the capacity of both antivenoms to immunocapture short neurotoxins being weaker than that for PLA2s.Conclusions: Our study clarified the venom-gland transcriptomic and venomic profiles along with the within-group divergence of a H. curtus population from the South China Sea. Adaptive evolution of most venom components driven by natural selection appeared to occur rapidly during evolutionary history. Notably, the utility of commercial N. atra and B. multicinctus antivenoms against H. curtus toxins was not comprehensive; thus, the development of species-specific antivenom is urgently needed.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 69%

Venom-gland Transcriptomic, Venomic, and Antivenomic Profiles of the Spine-bellied Sea Snake (Hydrophis curtus) from the South China Sea

Zhao

Wen

et al. 2020

Preprint

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“…The engineering of broad-spectrum AChBPs would ideally also use this humanized molecular backbone while taking advantage of the increased affinity (Nirthanan and Gwee, 2004) and pharmacological properties of other nAChR mimics, such as the Torpedo nAChR. Finally, while we explored the toxin capturing potential of AChBPs against a number of geographically diverse elapid snakes, such optimized broad-spectrum AChBPs would require testing against an increased breadth of venoms, including additional species within the elapid genera studied here and perhaps also members of the Hydrophiinae (marine elapids), whose venoms often contain abundant and highly potent α-neurotoxins that are typically not effectively neutralized by existing antivenoms (Tan et al, 2015; Tan et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

A Decoy-Receptor Approach Using Nicotinic Acetylcholine Receptor Mimics Reveals Their Potential as Novel Therapeutics Against Neurotoxic Snakebite

et al. 2019

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Snakebite is a neglected tropical disease that causes 138,000 deaths each year. Neurotoxic snake venoms contain small neurotoxins, including three-finger toxins (3FTxs), which can cause rapid paralysis in snakebite victims by blocking postsynaptic transmission via nicotinic acetylcholine receptors (nAChRs). These toxins are typically weakly immunogenic and thus are often not effectively targeted by current polyclonal antivenom therapies. We investigated whether nAChR mimics, also known as acetylcholine binding proteins (AChBPs), could effectively capture 3FTxs and therefore be developed as a novel class of snake-generic therapeutics for combatting neurotoxic envenoming. First, we identified the binding specificities of 3FTx from various medically important elapid snake venoms to nAChR using two recombinant nAChR mimics: the AChBP from Lymnaea stagnalis and a humanized neuronal α7 version (α7-AChBP). We next characterized these AChBP-bound and unbound fractions using SDS-PAGE and mass spectrometry. Interestingly, both mimics effectively captured long-chain 3FTxs from multiple snake species but largely failed to capture the highly related short-chain 3FTxs, suggesting a high level of binding specificity. We next investigated whether nAChR mimics could be used as snakebite therapeutics. We showed that while α7-AChBP alone did not protect against Naja haje (Egyptian cobra) venom lethality in vivo , it significantly prolonged survival times when coadministered with a nonprotective dose of antivenom. Thus, nAChR mimics are capable of neutralizing specific venom toxins and may be useful adjunct therapeutics for improving the safety and affordability of existing snakebite treatments by reducing therapeutic doses. Our findings justify exploring the future development of AChBPs as potential snakebite treatments.

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“…This wide range of ecologies representing different potential selection pressures make snakes an ideal system on which to test the role of trophic ecology on the evolution of predator traits. Previous studies have used snakes as a group to test the role of trophic ecology in driving venom composition [31][32][33][34], potency [24,[35][36][37], and the evolutionary atrophy of venom systems [38]. However, the use of non-standardised test models which typically do not represent natural prey species have previously confounded comparative analysis of venom potency [24,[39][40][41][42][43].…”

Section: Introductionmentioning

confidence: 99%

Diet Breadth Mediates the Prey Specificity of Venom Potency in Snakes

Lyons

Dugon

Healy

2020

Toxins

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Venoms are best known for their ability to incapacitate prey. In predatory groups, venom potency is predicted to reflect ecological and evolutionary drivers relating to diet. While venoms have been found to have prey-specific potencies, the role of diet breadth on venom potencies has yet to be tested at large macroecological scales. Here, using a comparative analysis of 100 snake species, we show that the evolution of prey-specific venom potencies is contingent on the breadth of a species’ diet. We find that while snake venom is more potent when tested on species closely related to natural prey items, we only find this prey-specific pattern in species with taxonomically narrow diets. While we find that the taxonomic diversity of a snakes’ diet mediates the prey specificity of its venom, the species richness of its diet was not found to affect these prey-specific potency patterns. This indicates that the physiological diversity of a species’ diet is an important driver of the evolution of generalist venom potencies. These findings suggest that the venoms of species with taxonomically diverse diets may be better suited to incapacitating novel prey species and hence play an important role for species within changing environments.

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Venom Proteome of Spine-Bellied Sea Snake (Hydrophis curtus) from Penang, Malaysia: Toxicity Correlation, Immunoprofiling and Cross-Neutralization by Sea Snake Antivenom

Cited by 41 publications

References 46 publications

Venom-gland Transcriptomic, Venomic, and Antivenomic Profiles of the Spine-bellied Sea Snake (Hydrophis curtus) from the South China Sea

Venom-gland Transcriptomic, Venomic, and Antivenomic Profiles of the Spine-bellied Sea Snake (Hydrophis curtus) from the South China Sea

A Decoy-Receptor Approach Using Nicotinic Acetylcholine Receptor Mimics Reveals Their Potential as Novel Therapeutics Against Neurotoxic Snakebite

Diet Breadth Mediates the Prey Specificity of Venom Potency in Snakes

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