An organotypic model of human skin simulates the dermonecrotic effects of Naja nigricollis envenoming

ABSTRACT: Snakebite envenoming is a neglected tropical disease that kills and maims hundreds of thousands annually. Naja nigricollis, the black-necked spitting cobra, has a cytotoxin-rich venom that is able to cause severe dermonecrosis and is not efficiently neutralized by current antivenoms. Here, we introduce an organotypic model of human skin to study the effects of exposure to N. nigricollis venom on human cells and compare it to the currently available in vivo mouse model. Histologically, the organotypic model simulates the severe necrotic lesions observed in mice. Proteomically, we show that among widespread global changes in protein abundance, many pathways involved in skin homeostasis and wound healing are specifically affected in both models. These results are the first to suggest that this organotypic model can simulate dermonecrosis caused by N. nigricollis venom and could thus be used to bridge the gap between in vitro and animal-based experiments for the study of the venom-induced cytotoxicity. This is an initial step towards replacing such animal-based experiments, which are associated with pain and tissue damage. The organotypic model may also find utility in evaluating the efficacy of new therapeutics against the severe and long-lasting consequences of snakebite envenoming in humans.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Cell Culture, Keratinocyte, Skin, Fibroblast

DISEASE(S): Wounds And Injuries

SUBMITTER: Ulrich auf dem Keller  

LAB HEAD: Ulrich auf dem Keller

PROVIDER: PXD033111 | Pride | 2023-01-11

REPOSITORIES: Pride