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

Georgia R Sampedro; Andrea C DeDent; Russell E N Becker; Bryan J Berube; Michael J Gebhardt; Hongyuan Cao; Juliane Bubeck Wardenburg

doi:10.1093/infdis/jiu223

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

Journal article

Open access

Peer reviewed

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

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

The Journal of infectious diseases, Vol.210(7), pp.1012-1018

10/01/2014

DOI: 10.1093/infdis/jiu223

PMCID: PMC4207862

PMID: 24740631

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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 dominant-negative 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.

Animals

Bacterial Toxins - antagonists & inhibitors

Bacterial Toxins - metabolism

Bacterial Toxins - toxicity

Hemolysin Proteins - antagonists & inhibitors

Hemolysin Proteins - metabolism

Hemolysin Proteins - toxicity

Male

Mice, Inbred C57BL

Recurrence

Soft Tissue Infections - drug therapy

Soft Tissue Infections - pathology

Staphylococcal Skin Infections - drug therapy

Staphylococcal Skin Infections - pathology

Staphylococcus aureus - metabolism

Staphylococcus aureus - physiology

Details

Title: Subtitle: Targeting Staphylococcus aureus α-toxin as a novel approach to reduce severity of recurrent skin and soft-tissue infections
Creators: Georgia R Sampedro - 1Department of Pediatrics
Andrea C DeDent - 1Department of Pediatrics
Russell E N Becker - Department of Microbiology
Bryan J Berube - Department of Microbiology
Michael J Gebhardt - Department of Microbiology
Hongyuan Cao - University of Chicago
Juliane Bubeck Wardenburg - Department of Pediatrics Department of Microbiology
Resource Type: Journal article
Publication Details: The Journal of infectious diseases, Vol.210(7), pp.1012-1018
DOI: 10.1093/infdis/jiu223
PMID: 24740631
PMCID: PMC4207862
NLM abbreviation: J Infect Dis
ISSN: 0022-1899
eISSN: 1537-6613
Grant note: GM007281 / NIGMS NIH HHS T32 GM007281 / NIGMS NIH HHS AI097434-01 / NIAID NIH HHS T32 GM007183 / NIGMS NIH HHS UL1 TR000430 / NCATS NIH HHS U54 AI057153 / NIAID NIH HHS R01 AI097434 / NIAID NIH HHS 2-U54-AI-057153 / NIAID NIH HHS
Language: English
Date published: 10/01/2014
Academic Unit: Microbiology and Immunology
Record Identifier: 9984297328702771

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