The medical threat of mamba envenoming in sub-Saharan Africa revealed by genus-wide analysis of venom composition, toxicity and antivenomics profiling of available antivenoms.

Ainsworth, Stuart ORCID: https://orcid.org/0000-0002-0199-6482, Petras, Daniel, Engmark, Mikael, Sussmuth, Roderich, Whiteley, Gareth, Albulescu, Laura-Oana ORCID: https://orcid.org/0000-0001-6563-9217, Kazandijan, Taline D, Wagstaff, Simon ORCID: https://orcid.org/0000-0003-0577-5537, Rowley, Paul, Wüster, Wolfgang, Dorrestein, Pieter C., Arias, Ana Silvia, Gutiérrez, José M., Harrison, Robert, Casewell, Nicholas ORCID: https://orcid.org/0000-0002-8035-4719 and Calvete, Juan J (2018) 'The medical threat of mamba envenoming in sub-Saharan Africa revealed by genus-wide analysis of venom composition, toxicity and antivenomics profiling of available antivenoms.'. Journal of Proteomics, Vol 192, pp. 173-189.

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Abstract

Mambas (genus Dendroaspis) are among the most feared of the medically important elapid snakes found in sub-Saharan Africa, but many facets of their biology, including the diversity of venom composition, remain relatively understudied. Here, we present a reconstruction of mamba phylogeny, alongside genus-wide venom gland transcriptomic and high-resolution top-down venomic analyses. Whereas the green mambas, D. viridis, D. angusticeps, D. j. jamesoni and D. j. kaimosae, express 3FTx-predominant venoms, black mamba (D. polylepis) venom is dominated by dendrotoxins I and K. The divergent terrestrial ecology of D. polylepis compared to the arboreal niche occupied by all other mambas makes it plausible that this major difference in venom composition is due to dietary variation. The pattern of intrageneric venom variability across Dendroaspis represented a valuable opportunity to investigate, in a genus-wide context, the variant toxicity of the venom, and the degree of paraspecific cross-reactivity between antivenoms and mamba venoms. To this end, the immunological profiles of the five mamba venoms were assessed against a panel of commercial antivenoms generated for the sub-Saharan Africa market. This study provides a genus-wide overview of which available antivenoms may be more efficacious in neutralising human envenomings caused by mambas, irrespective of the species responsible. The information gathered in this study lays the foundations for rationalising the notably different potency and pharmacological profiles of Dendroaspis venoms at locus resolution. This understanding will allow selection and design of toxin immunogens with a view to generating a safer and more efficacious pan-specific antivenom against any mamba envenomation.

Item Type:	Article
Subjects:	QV Pharmacology > Toxicology > General Toxicology > QV 600 General works QV Pharmacology > Toxicology > General Toxicology > QV 601 Antidotes and other therapeutic measures QW Microbiology and Immunology > QW 4 General works. Classify here works on microbiology as a whole. QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 630 Toxins. Antitoxins WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.jprot.2017.08.016
Depositing User:	Stacy Murtagh
Date Deposited:	12 Sep 2017 14:05
Last Modified:	17 Sep 2019 13:33
URI:	https://archive.lstmed.ac.uk/id/eprint/7572

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