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Venom proteome of the yellow-lipped sea krait, Laticauda colubrina from Bali: Insights into subvenomic diversity, venom antigenicity and cross-neutralization by antivenom.
J Proteomics. 2017 08 23; 166:48-58.JP

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: tanch@um.edu.my.Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28688916

Citation

Tan, Choo Hock, et al. "Venom Proteome of the Yellow-lipped Sea Krait, Laticauda Colubrina From Bali: Insights Into Subvenomic Diversity, Venom Antigenicity and Cross-neutralization By Antivenom." Journal of Proteomics, vol. 166, 2017, pp. 48-58.
Tan CH, Wong KY, Tan KY, et al. Venom proteome of the yellow-lipped sea krait, Laticauda colubrina from Bali: Insights into subvenomic diversity, venom antigenicity and cross-neutralization by antivenom. J Proteomics. 2017;166:48-58.
Tan, C. H., Wong, K. Y., Tan, K. Y., & Tan, N. H. (2017). Venom proteome of the yellow-lipped sea krait, Laticauda colubrina from Bali: Insights into subvenomic diversity, venom antigenicity and cross-neutralization by antivenom. Journal of Proteomics, 166, 48-58. https://doi.org/10.1016/j.jprot.2017.07.002
Tan CH, et al. Venom Proteome of the Yellow-lipped Sea Krait, Laticauda Colubrina From Bali: Insights Into Subvenomic Diversity, Venom Antigenicity and Cross-neutralization By Antivenom. J Proteomics. 2017 08 23;166:48-58. PubMed PMID: 28688916.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Venom proteome of the yellow-lipped sea krait, Laticauda colubrina from Bali: Insights into subvenomic diversity, venom antigenicity and cross-neutralization by antivenom. AU - Tan,Choo Hock, AU - Wong,Kin Ying, AU - Tan,Kae Yi, AU - Tan,Nget Hong, Y1 - 2017/07/05/ PY - 2017/05/21/received PY - 2017/06/28/revised PY - 2017/07/02/accepted PY - 2017/7/10/pubmed PY - 2018/6/19/medline PY - 2017/7/10/entrez SP - 48 EP - 58 JF - Journal of proteomics JO - J Proteomics VL - 166 N2 - : 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. SN - 1876-7737 UR - https://www.unboundmedicine.com/medline/citation/28688916/Venom_proteome_of_the_yellow_lipped_sea_krait_Laticauda_colubrina_from_Bali:_Insights_into_subvenomic_diversity_venom_antigenicity_and_cross_neutralization_by_antivenom_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1874-3919(17)30236-1 DB - PRIME DP - Unbound Medicine ER -