Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 210, Issue 7, Pages 1012-1018Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiu223
Keywords
Staphylococcus aureus; skin and soft-tissue infection; alpha-toxin; recurrent infection; novel therapeutics
Categories
Funding
- National Institutes of Heath (NIH) [AI097434-01]
- Burroughs Wellcome Foundation
- Region V Great Lakes Regional Center of Excellence (RCE) (RCE, NIH) [2-U54-AI-057153]
- NIH Medical Scientist Training Program at the University of Chicago [GM007281]
- National Institutes of Health [T32 GM007183]
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Staphyococcus aureus frequently causes recurrent skin and soft-tissue infection (SSTI). In the pediatric population, elevated serum antibody targeting S. aureus alpha-toxin is correlated with a reduced incidence of recurrent SSTI. Using a novel model of recurrent SSTI, we demonstrated that expression of a-toxin during primary infection increases the severity of recurrent disease. Antagonism of alpha-toxin by either a dominant-negative toxin mutant or a small molecule inhibitor of the toxin receptor ADAM10 during primary infection reduces reinfection abscess severity. Early neutralization of a-toxin activity during S. aureus SSTI therefore offers a new therapeutic strategy to mitigate primary and recurrent disease.
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