dc.contributor.author
Winter, Sebastian Virreira
dc.contributor.author
Zychlinsky, Arturo
dc.contributor.author
Bardoel, Bart W.
dc.date.accessioned
2018-06-08T02:57:15Z
dc.date.available
2016-05-09T09:40:45.573Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/14199
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-18396
dc.description.abstract
Staphylococcus aureus causes a wide variety of infections and antibiotic
resistant strains are a major problem in hospitals. One of the best studied
virulence factors of S. aureus is the pore-forming toxin alpha hemolysin (αHL)
whose mechanism of action is incompletely understood. We performed a genome-
wide loss-of-function screen using CRISPR/Cas9 technology to identify host
targets required for αHL susceptibility in human myeloid cells. We found gRNAs
for ten genes enriched after intoxication with αHL and focused on the top five
hits. Besides a disintegrin and metalloproteinase domain-containing protein 10
(ADAM10), the host receptor for αHL, we identified three proteins, Sys1 golgi
trafficking protein (SYS1), ADP-ribosylation factor 1 (ARFRP1), and
tetraspanin-14 (TSPAN14) which regulate the presentation of ADAM10 on the
plasma membrane post-translationally. Interestingly, we also showed that cells
lacking sphingomyelin synthase 1 (SGMS1) resist αHL intoxication, but have
only a slightly reduced ADAM10 surface expression. SGMS1 regulates lipid raft
formation, suggesting that αHL requires these membrane microdomains for
attachment and cytotoxicity.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Genome-wide CRISPR screen reveals novel host factors required for
Staphylococcus aureus α-hemolysin-mediated toxicity
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Scientific Reports. - 6 (2016), Artikel Nr. 24242
dcterms.bibliographicCitation.doi
10.1038/srep24242
dcterms.bibliographicCitation.url
http://www.nature.com/articles/srep24242
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000024483
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000006372
dcterms.accessRights.openaire
open access