ADAM10 mediates vascular injury induced by staphylococcus aureus α-hemolysin

Michael E. Powers, Hwan Keun Kim, Yang Wang, Juliane Bubeck Wardenburg

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

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.

Original languageEnglish
Pages (from-to)352-356
Number of pages5
JournalJournal of Infectious Diseases
Volume206
Issue number3
DOIs
StatePublished - Aug 1 2012

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