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J Infect Dis. 2012 Aug 1;206(3):352-6. doi: 10.1093/infdis/jis192. Epub 2012 Apr 2.

ADAM10 mediates vascular injury induced by Staphylococcus aureus α-hemolysin.

Author information

1
Department of Microbiology, The University of Chicago, Illinois 60637, USA.

Abstract

Staphylococcus aureus is a leading cause of bacteremia and sepsis. The interaction of S. aureus with the endothelium is central to bloodstream infection pathophysiology yet remains ill-understood. We show herein that staphylococcal α-hemolysin, a pore-forming cytotoxin, is required for full virulence in a murine sepsis model. The α-hemolysin binding to its receptor A-disintegrin and metalloprotease 10 (ADAM10) upregulates the receptor's metalloprotease activity on endothelial cells, causing vascular endothelial-cadherin cleavage and concomitant loss of endothelial barrier function. These cellular injuries and sepsis severity can be mitigated by ADAM10 inhibition. This study therefore provides mechanistic insight into toxin-mediated endothelial injury and suggests new therapeutic approaches for staphylococcal sepsis.

PMID:
22474035
PMCID:
PMC3392186
DOI:
10.1093/infdis/jis192
[Indexed for MEDLINE]
Free PMC Article

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