title: Targeting Staphylococcus aureus α-toxin as a novel approach to reduce severity of recurrent skin and soft-tissue infections.
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.
authors.affiliation: Department of Pediatrics Department of Microbiology.
authors.forename: Georgia R
authors.initials: GR
authors.lastname: Sampedro
authors.affiliation: Department of Pediatrics Department of Microbiology.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: DeDent
authors.affiliation: Department of Microbiology.
authors.forename: Russell E N
authors.initials: RE
authors.lastname: Becker
authors.affiliation: Department of Microbiology.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Berube
authors.affiliation: Department of Microbiology.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gebhardt
authors.affiliation: Department of Health Studies, University of Chicago, Illinois.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Pediatrics Department of Microbiology.
authors.forename: Juliane
authors.initials: J
authors.lastname: Bubeck Wardenburg
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D006460:Hemolysin Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D008810:Mice, Inbred C57BL; D012008:Recurrence; D018461:Soft Tissue Infections / Q000188:drug therapy / Q000473:pathology*; D013207:Staphylococcal Skin Infections / Q000188:drug therapy / Q000473:pathology*; D013211:Staphylococcus aureus / Q000378:metabolism / Q000502:physiology*
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin
keywords: Staphylococcus aureus; novel therapeutics; recurrent infection; skin and soft-tissue infection; α-toxin
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