Unveiling the nature of black mamba (Dendroaspis polylepis) venom through venomics and antivenom immunoprofiling: Identification of key toxin targets for antivenom development
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Unveiling the nature of black mamba (Dendroaspis polylepis) venom through venomics and antivenom immunoprofiling: Identification of key toxin targets for antivenom development. / Laustsen, Andreas Hougaard; Lomonte, Bruno; Lohse, Brian; Fernandez, Julian; Gutiérrez, José María.
I: Journal of Proteomics, Bind 119, 2015, s. 126–142.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Unveiling the nature of black mamba (Dendroaspis polylepis) venom through venomics and antivenom immunoprofiling: Identification of key toxin targets for antivenom development
AU - Laustsen, Andreas Hougaard
AU - Lomonte, Bruno
AU - Lohse, Brian
AU - Fernandez, Julian
AU - Gutiérrez, José María
PY - 2015
Y1 - 2015
N2 - The venom proteome of the black mamba, Dendroaspis polylepis, from Eastern Africa, was, for the first time, characterized. Forty- different proteins and one nucleoside were identified or assigned to protein families. The most abundant proteins were Kunitz-type proteinase inhibitors, which include the unique mamba venom components ‘dendrotoxins’, and α-neurotoxins and other representatives of the three-finger toxin family. In addition, the venom contains lower percentages of proteins from other families, including metalloproteinase, hyaluronidase, prokineticin, nerve growth factor, vascular endothelial growth factor, phospholipase A2, 5′-nucleotidase, and phosphodiesterase. Assessment of acute toxicity revealed that the most lethal components were α-neurotoxins and, to a lower extent, dendrotoxins. This venom also contains a relatively high concentration of adenosine, which might contribute to toxicity by influencing the toxin biodistribution. ELISA immunoprofiling and preclinical assessment of neutralization showed that polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of D. polylepis venom, albeit showing different potencies. Antivenoms had higher antibody titers against α-neurotoxins than against dendrotoxins, and displayed high titers against less toxic proteins of high molecular mass. Our results reveal the complexity of D. polylepis venom, and provide information for the identification of its most relevant toxins to be neutralized by antivenoms.
AB - The venom proteome of the black mamba, Dendroaspis polylepis, from Eastern Africa, was, for the first time, characterized. Forty- different proteins and one nucleoside were identified or assigned to protein families. The most abundant proteins were Kunitz-type proteinase inhibitors, which include the unique mamba venom components ‘dendrotoxins’, and α-neurotoxins and other representatives of the three-finger toxin family. In addition, the venom contains lower percentages of proteins from other families, including metalloproteinase, hyaluronidase, prokineticin, nerve growth factor, vascular endothelial growth factor, phospholipase A2, 5′-nucleotidase, and phosphodiesterase. Assessment of acute toxicity revealed that the most lethal components were α-neurotoxins and, to a lower extent, dendrotoxins. This venom also contains a relatively high concentration of adenosine, which might contribute to toxicity by influencing the toxin biodistribution. ELISA immunoprofiling and preclinical assessment of neutralization showed that polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of D. polylepis venom, albeit showing different potencies. Antivenoms had higher antibody titers against α-neurotoxins than against dendrotoxins, and displayed high titers against less toxic proteins of high molecular mass. Our results reveal the complexity of D. polylepis venom, and provide information for the identification of its most relevant toxins to be neutralized by antivenoms.
KW - Faculty of Health and Medical Sciences
KW - Dendroaspis polylepis
KW - Antivenoms
KW - Immunoprofiling
KW - Snake venom: proteomics
KW - Black mamba
U2 - 10.1016/j.jprot.2015.02.002
DO - 10.1016/j.jprot.2015.02.002
M3 - Journal article
C2 - 25688917
VL - 119
SP - 126
EP - 142
JO - Journal of Proteomics
JF - Journal of Proteomics
SN - 1874-3919
ER -
ID: 134704827