Tags

Type your tag names separated by a space and hit enter

Proteomics and antivenomics of Papuan black snake (Pseudechis papuanus) venom with analysis of its toxicological profile and the preclinical efficacy of Australian antivenoms.
J Proteomics. 2017 01 06; 150:201-215.JP

Abstract

The Papuan black snake (Pseudechis papuanus Serpentes: Elapidae) is endemic to Papua New Guinea, Indonesian Papua and Australia's Torres Strait Islands. We have investigated the biological activity and proteomic composition of its venom. The P. papuanus venom proteome is dominated by a variety (n≥18) of PLA2s, which together account for ~90% of the venom proteins, and a set of low relative abundance proteins, including a short-neurotoxic 3FTx (3.1%), 3-4 PIII-SVMPs (2.8%), 3 cysteine-rich secretory proteins (CRISP; 2.3%) 1-3 l-amino acid oxidase (LAAO) molecules (1.6%). Probing of a P. papuanus cDNA library with specific primers resulted in the elucidation of the full-length nucleotide sequences of six new toxins, including vespryn and NGF not found in the venom proteome, and a calglandulin protein involved in toxin expression with the venom glands. Intravenous injection of P. papuanus venom in mice induced lethality, intravascular haemolysis, pulmonary congestion and oedema, and anticoagulation after intravenous injection, and these effects are mainly due to the action of PLA2s. This study also evaluated the in vivo preclinical efficacy of Australian black snake and polyvalent Seqirus antivenoms. These antivenoms were effective in neutralising the lethal, PLA2 and anticoagulant activities of P. papuanus venom in mice. On the other hand, all of the Seqirus antivenoms tested using an antivenomic approach exhibited strong immunorecognition of all the venom components. These preclinical results suggest that Australian Seqirus1 antivenoms may provide paraspecific protection against P. papuanus venom in humans.

SIGNIFICANCE PARAGRAPH

The toxicological profile and proteomic composition of the venom of the Papuan black snake, Pseudechis papuanus, a large diurnal snake endemic to the southern coast of New Guinea and a handful of close offshore islands, were investigated. Intravenous injection of P. papuanus venom in mice induced intravascular hemolysis, pulmonary congestion and edema, anticoagulation, and death. These activities could be assigned to the set of PLA2 molecules, which dominate the P. papuanus venom proteome. This study also showed that Australian Seqirus black snake or polyvalent antivenoms were effective in neutralising the lethal, PLA2 and anticoagulant activities of the venom. These preclinical results support the continued recommendation of these Seqirus antivenoms in the clinical management of P. papuanus envenoming in Australia, Papua New Guinea or Indonesian Papua Province.

Authors+Show Affiliations

Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (CSIC), Valencia, Spain.Charles Campbell Toxinology Centre, School of Medicine & Health Sciences, University of Papua New Guinea, Boroko, NCD, Papua New Guinea.Australian Venom Research Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia.Charles Campbell Toxinology Centre, School of Medicine & Health Sciences, University of Papua New Guinea, Boroko, NCD, Papua New Guinea.Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (CSIC), Valencia, Spain.Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.Australian Venom Research Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia; Cardiovascular Therapeutics Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Victoria 3010, Australia.Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (CSIC), Valencia, Spain. Electronic address: jcalvete@ibv.csic.es.Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica. Electronic address: jose.gutierrez@ucr.ac.cr.Charles Campbell Toxinology Centre, School of Medicine & Health Sciences, University of Papua New Guinea, Boroko, NCD, Papua New Guinea; Australian Venom Research Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: david.williams@unimelb.edu.au.

Pub Type(s)

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

Language

eng

PubMed ID

27650695

Citation

Pla, Davinia, et al. "Proteomics and Antivenomics of Papuan Black Snake (Pseudechis Papuanus) Venom With Analysis of Its Toxicological Profile and the Preclinical Efficacy of Australian Antivenoms." Journal of Proteomics, vol. 150, 2017, pp. 201-215.
Pla D, Bande BW, Welton RE, et al. Proteomics and antivenomics of Papuan black snake (Pseudechis papuanus) venom with analysis of its toxicological profile and the preclinical efficacy of Australian antivenoms. J Proteomics. 2017;150:201-215.
Pla, D., Bande, B. W., Welton, R. E., Paiva, O. K., Sanz, L., Segura, Á., Wright, C. E., Calvete, J. J., Gutiérrez, J. M., & Williams, D. J. (2017). Proteomics and antivenomics of Papuan black snake (Pseudechis papuanus) venom with analysis of its toxicological profile and the preclinical efficacy of Australian antivenoms. Journal of Proteomics, 150, 201-215. https://doi.org/10.1016/j.jprot.2016.09.007
Pla D, et al. Proteomics and Antivenomics of Papuan Black Snake (Pseudechis Papuanus) Venom With Analysis of Its Toxicological Profile and the Preclinical Efficacy of Australian Antivenoms. J Proteomics. 2017 01 6;150:201-215. PubMed PMID: 27650695.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Proteomics and antivenomics of Papuan black snake (Pseudechis papuanus) venom with analysis of its toxicological profile and the preclinical efficacy of Australian antivenoms. AU - Pla,Davinia, AU - Bande,Benjamin W, AU - Welton,Ronelle E, AU - Paiva,Owen K, AU - Sanz,Libia, AU - Segura,Álvaro, AU - Wright,Christine E, AU - Calvete,Juan J, AU - Gutiérrez,José María, AU - Williams,David J, Y1 - 2016/09/17/ PY - 2016/08/13/received PY - 2016/09/15/revised PY - 2016/09/16/accepted PY - 2016/10/25/pubmed PY - 2017/12/5/medline PY - 2016/9/22/entrez KW - Antivenomics KW - In vivo neutralisation KW - Lethality KW - Myotoxicity KW - Pseudechis papuanus KW - Seqirus antivenoms KW - Snake venomics SP - 201 EP - 215 JF - Journal of proteomics JO - J Proteomics VL - 150 N2 - : The Papuan black snake (Pseudechis papuanus Serpentes: Elapidae) is endemic to Papua New Guinea, Indonesian Papua and Australia's Torres Strait Islands. We have investigated the biological activity and proteomic composition of its venom. The P. papuanus venom proteome is dominated by a variety (n≥18) of PLA2s, which together account for ~90% of the venom proteins, and a set of low relative abundance proteins, including a short-neurotoxic 3FTx (3.1%), 3-4 PIII-SVMPs (2.8%), 3 cysteine-rich secretory proteins (CRISP; 2.3%) 1-3 l-amino acid oxidase (LAAO) molecules (1.6%). Probing of a P. papuanus cDNA library with specific primers resulted in the elucidation of the full-length nucleotide sequences of six new toxins, including vespryn and NGF not found in the venom proteome, and a calglandulin protein involved in toxin expression with the venom glands. Intravenous injection of P. papuanus venom in mice induced lethality, intravascular haemolysis, pulmonary congestion and oedema, and anticoagulation after intravenous injection, and these effects are mainly due to the action of PLA2s. This study also evaluated the in vivo preclinical efficacy of Australian black snake and polyvalent Seqirus antivenoms. These antivenoms were effective in neutralising the lethal, PLA2 and anticoagulant activities of P. papuanus venom in mice. On the other hand, all of the Seqirus antivenoms tested using an antivenomic approach exhibited strong immunorecognition of all the venom components. These preclinical results suggest that Australian Seqirus1 antivenoms may provide paraspecific protection against P. papuanus venom in humans. SIGNIFICANCE PARAGRAPH: The toxicological profile and proteomic composition of the venom of the Papuan black snake, Pseudechis papuanus, a large diurnal snake endemic to the southern coast of New Guinea and a handful of close offshore islands, were investigated. Intravenous injection of P. papuanus venom in mice induced intravascular hemolysis, pulmonary congestion and edema, anticoagulation, and death. These activities could be assigned to the set of PLA2 molecules, which dominate the P. papuanus venom proteome. This study also showed that Australian Seqirus black snake or polyvalent antivenoms were effective in neutralising the lethal, PLA2 and anticoagulant activities of the venom. These preclinical results support the continued recommendation of these Seqirus antivenoms in the clinical management of P. papuanus envenoming in Australia, Papua New Guinea or Indonesian Papua Province. SN - 1876-7737 UR - https://www.unboundmedicine.com/medline/citation/27650695/Proteomics_and_antivenomics_of_Papuan_black_snake__Pseudechis_papuanus__venom_with_analysis_of_its_toxicological_profile_and_the_preclinical_efficacy_of_Australian_antivenoms_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1874-3919(16)30418-3 DB - PRIME DP - Unbound Medicine ER -