Tags

Type your tag names separated by a space and hit enter

Toxicovenomics and antivenom profiling of the Eastern green mamba snake (Dendroaspis angusticeps).
J Proteomics. 2016 Mar 16; 136:248-61.JP

Abstract

A toxicovenomic study was performed on the venom of the green mamba, Dendroaspis angusticeps. Forty-two different proteins were identified in the venom of D. angusticeps, in addition to the nucleoside adenosine. The most abundant proteins belong to the three-finger toxin (3FTx) (69.2%) and the Kunitz-type proteinase inhibitor (16.3%) families. Several sub-subfamilies of the 3FTxs were identified, such as Orphan Group XI (Toxin F-VIII), acetylcholinesterase inhibitors (fasciculins), and aminergic toxins (muscarinic toxins, synergistic-like toxins, and adrenergic toxins). Remarkably, no α-neurotoxins were identified. Proteins of the Kunitz-type proteinase inhibitor family include dendrotoxins. Toxicological screening revealed a lack of lethal activity in all RP-HPLC fractions, except one, at the doses tested. Thus, the overall toxicity depends on the synergistic action of various types of proteins, such as dendrotoxins, fasciculins, and probably other synergistically-acting toxins. Polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of venom-induced lethality. These antivenoms also showed a pattern of broad immunorecognition of the different HPLC fractions by ELISA and immunoprecipitated the crude venom by gel immunodiffusion. The synergistic mechanism of toxicity constitutes a challenge for the development of effective recombinant antibodies, as it requires the identification of the most relevant synergistic toxins.

BIOLOGICAL SIGNIFICANCE

Envenomings by elapid snakes of the genus Dendroaspis, collectively known as mambas, represent a serious medical problem in sub-Saharan Africa. The development of novel antivenoms and of recombinant neutralizing antibodies demands the identification of the most relevant toxins in these venoms. In this study, a bottom-up approach was followed for the study of the proteome of the venom of the Eastern green mamba, D. angusticeps. Forty-two different proteins were identified, among which the three-finger toxin (3FTx) family, characteristic of elapid venoms, was the most abundant, followed by the Kunitz-type proteinase inhibitor family. In addition, several other protein families were present in the venom, together with the nucleoside adenosine. No α-neurotoxins were identified within the family of 3FTxs in the venom of D. angusticeps, in contrast to the venom of Dendroaspis polylepis, in which α-neurotoxins are largely responsible for the toxicity. With one exception, HPLC fractions from D. angusticeps venom did not kill mice at the doses tested. This underscores that the toxicity of the whole venom is due to the synergistic action of various components, such as fasciculins and dendrotoxins, and probably other synergistically-acting toxins. Thus, the venoms of these closely related species (D. angusticeps and D. polylepis) seem to have different mechanisms to subdue their prey, which may be related to different prey preferences, as D. angusticeps is predominantly arboreal, whereas D. polylepis lives mostly in open bush country and feeds mainly on mammals. It is therefore likely that the predominant clinical manifestations of human envenomings by these species also differ, although in both cases neurotoxic manifestations predominate. Polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of venom-induced lethality in mice and showed a pattern of broad immunorecognition of the various venom fractions. It is necessary to identify the toxins responsible for the synergistic mode of toxicity in this venom, since they are the targets for the development of recombinant antibodies for the treatment of envenomings.

Authors+Show Affiliations

Department of Systems Biology, Technical University of Denmark, Denmark.Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica. Electronic address: jose.gutierrez@ucr.ac.cr.

Pub Type(s)

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

Language

eng

PubMed ID

26877184

Citation

Lauridsen, Line P., et al. "Toxicovenomics and Antivenom Profiling of the Eastern Green Mamba Snake (Dendroaspis Angusticeps)." Journal of Proteomics, vol. 136, 2016, pp. 248-61.
Lauridsen LP, Laustsen AH, Lomonte B, et al. Toxicovenomics and antivenom profiling of the Eastern green mamba snake (Dendroaspis angusticeps). J Proteomics. 2016;136:248-61.
Lauridsen, L. P., Laustsen, A. H., Lomonte, B., & Gutiérrez, J. M. (2016). Toxicovenomics and antivenom profiling of the Eastern green mamba snake (Dendroaspis angusticeps). Journal of Proteomics, 136, 248-61. https://doi.org/10.1016/j.jprot.2016.02.003
Lauridsen LP, et al. Toxicovenomics and Antivenom Profiling of the Eastern Green Mamba Snake (Dendroaspis Angusticeps). J Proteomics. 2016 Mar 16;136:248-61. PubMed PMID: 26877184.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Toxicovenomics and antivenom profiling of the Eastern green mamba snake (Dendroaspis angusticeps). AU - Lauridsen,Line P, AU - Laustsen,Andreas H, AU - Lomonte,Bruno, AU - Gutiérrez,José María, Y1 - 2016/02/12/ PY - 2016/01/15/received PY - 2016/02/08/revised PY - 2016/02/09/accepted PY - 2016/2/16/entrez PY - 2016/2/16/pubmed PY - 2016/12/15/medline KW - Dendroaspis angusticeps KW - Green mamba KW - Proteomics KW - Snake venom KW - Toxicovenomics: antivenoms SP - 248 EP - 61 JF - Journal of proteomics JO - J Proteomics VL - 136 N2 - UNLABELLED: A toxicovenomic study was performed on the venom of the green mamba, Dendroaspis angusticeps. Forty-two different proteins were identified in the venom of D. angusticeps, in addition to the nucleoside adenosine. The most abundant proteins belong to the three-finger toxin (3FTx) (69.2%) and the Kunitz-type proteinase inhibitor (16.3%) families. Several sub-subfamilies of the 3FTxs were identified, such as Orphan Group XI (Toxin F-VIII), acetylcholinesterase inhibitors (fasciculins), and aminergic toxins (muscarinic toxins, synergistic-like toxins, and adrenergic toxins). Remarkably, no α-neurotoxins were identified. Proteins of the Kunitz-type proteinase inhibitor family include dendrotoxins. Toxicological screening revealed a lack of lethal activity in all RP-HPLC fractions, except one, at the doses tested. Thus, the overall toxicity depends on the synergistic action of various types of proteins, such as dendrotoxins, fasciculins, and probably other synergistically-acting toxins. Polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of venom-induced lethality. These antivenoms also showed a pattern of broad immunorecognition of the different HPLC fractions by ELISA and immunoprecipitated the crude venom by gel immunodiffusion. The synergistic mechanism of toxicity constitutes a challenge for the development of effective recombinant antibodies, as it requires the identification of the most relevant synergistic toxins. BIOLOGICAL SIGNIFICANCE: Envenomings by elapid snakes of the genus Dendroaspis, collectively known as mambas, represent a serious medical problem in sub-Saharan Africa. The development of novel antivenoms and of recombinant neutralizing antibodies demands the identification of the most relevant toxins in these venoms. In this study, a bottom-up approach was followed for the study of the proteome of the venom of the Eastern green mamba, D. angusticeps. Forty-two different proteins were identified, among which the three-finger toxin (3FTx) family, characteristic of elapid venoms, was the most abundant, followed by the Kunitz-type proteinase inhibitor family. In addition, several other protein families were present in the venom, together with the nucleoside adenosine. No α-neurotoxins were identified within the family of 3FTxs in the venom of D. angusticeps, in contrast to the venom of Dendroaspis polylepis, in which α-neurotoxins are largely responsible for the toxicity. With one exception, HPLC fractions from D. angusticeps venom did not kill mice at the doses tested. This underscores that the toxicity of the whole venom is due to the synergistic action of various components, such as fasciculins and dendrotoxins, and probably other synergistically-acting toxins. Thus, the venoms of these closely related species (D. angusticeps and D. polylepis) seem to have different mechanisms to subdue their prey, which may be related to different prey preferences, as D. angusticeps is predominantly arboreal, whereas D. polylepis lives mostly in open bush country and feeds mainly on mammals. It is therefore likely that the predominant clinical manifestations of human envenomings by these species also differ, although in both cases neurotoxic manifestations predominate. Polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of venom-induced lethality in mice and showed a pattern of broad immunorecognition of the various venom fractions. It is necessary to identify the toxins responsible for the synergistic mode of toxicity in this venom, since they are the targets for the development of recombinant antibodies for the treatment of envenomings. SN - 1876-7737 UR - https://www.unboundmedicine.com/medline/citation/26877184/Toxicovenomics_and_antivenom_profiling_of_the_Eastern_green_mamba_snake__Dendroaspis_angusticeps__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1874-3919(16)30026-4 DB - PRIME DP - Unbound Medicine ER -