Targeting Staphylococcus aureus α-toxin as a novel approach to reduce severity of recurrent skin and soft-tissue infections

Georgia R. Sampedro, Andrea C. De Dent, Russell E.N. Becker, Bryan J. Berube, Michael J. Gebhardt, Hongyuan Cao, Juliane Bubeck Wardenburg

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Staphyococcus aureus frequently causes recurrent skin and soft-tissue infection (SSTI). In the pediatric population, elevated serum antibody targeting S. aureus α-toxin is correlated with a reduced incidence of recurrent SSTI. Using a novel model of recurrent SSTI, we demonstrated that expression of α-toxin during primary infection increases the severity of recurrent disease. Antagonism of α-toxin by either a dominantnegative toxin mutant or a small molecule inhibitor of the toxin receptor ADAM10 during primary infection reduces reinfection abscess severity. Early neutralization of α-toxin activity during S. aureus SSTI therefore offers a new therapeutic strategy to mitigate primary and recurrent disease.

Original languageEnglish
Pages (from-to)1012-1018
Number of pages7
JournalJournal of Infectious Diseases
Volume210
Issue number7
DOIs
StatePublished - 2014

Keywords

  • Novel therapeutics
  • Recurrent infection
  • Skin and soft-tissue infection
  • Staphylococcus aureus
  • α-toxin

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