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Molecular dissection of box jellyfish venom cytotoxicity highlights an effective venom antidote
- Source :
- Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019), Nature Communications
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- The box jellyfish Chironex fleckeri is extremely venomous, and envenoming causes tissue necrosis, extreme pain and death within minutes after severe exposure. Despite rapid and potent venom action, basic mechanistic insight is lacking. Here we perform molecular dissection of a jellyfish venom-induced cell death pathway by screening for host components required for venom exposure-induced cell death using genome-scale lenti-CRISPR mutagenesis. We identify the peripheral membrane protein ATP2B1, a calcium transporting ATPase, as one host factor required for venom cytotoxicity. Targeting ATP2B1 prevents venom action and confers long lasting protection. Informatics analysis of host genes required for venom cytotoxicity reveal pathways not previously implicated in cell death. We also discover a venom antidote that functions up to 15 minutes after exposure and suppresses tissue necrosis and pain in mice. These results highlight the power of whole genome CRISPR screening to investigate venom mechanisms of action and to rapidly identify new medicines.<br />Box jellyfish venom causes tissue damage, pain, and death through unknown molecular mechanisms. Here, Lau et al. perform a CRISPR screen to identify genes required for venom action and use this information to develop an antidote that blocks venom-induced pain and tissue damage in vivo.
- Subjects :
- Cell death
Male
0301 basic medicine
Programmed cell death
Jellyfish
Cell Survival
Science
Antidotes
Blotting, Western
General Physics and Astronomy
Poison control
Venom
02 engineering and technology
Pharmacology
complex mixtures
Article
General Biochemistry, Genetics and Molecular Biology
Mice
Necrosis
03 medical and health sciences
Cnidarian Venoms
Chironex fleckeri
biology.animal
Box jellyfish
Animals
lcsh:Science
Cytotoxicity
Cumulus Cells
Multidisciplinary
biology
Drug discovery
General Chemistry
021001 nanoscience & nanotechnology
biology.organism_classification
Sphingomyelins
3. Good health
Mechanisms of disease
Gene Ontology
030104 developmental biology
Calcium transporting ATPase
Cubozoa
Calcium
lcsh:Q
0210 nano-technology
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....6710d450790a3ed5bf91fde472034ebe