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

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 ?-hemolysin, a pore-forming cytotoxin, is required for full virulence in a murine sepsis model. The ?-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.

SUBMITTER: Powers ME

PROVIDER: S-EPMC3392186 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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

Powers Michael E ME Kim Hwan Keun HK Wang Yang Y Bubeck Wardenburg Juliane J

The Journal of infectious diseases 20120402 3

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 vasc ...[more]

PMID: 22474035

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Host Response Signature to Staphylococcus aureus alpha-Hemolysin

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An important role of ?-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.

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