Abstract
Exfoliative toxin (ET) is secreted by Staphylococcus aureus and has long been known to cause localized or widespread epidermal blistering in humans termed bullous impetigo or staphylococcal scalded-skin syndrome, respectively. While initial hypotheses suggested that ET was a superantigen, sequence and crystallographic analysis characterized the toxin as a serine protease. More recent work determined that ET cleaves a desmosomal cadherin, desmoglein (Dsg)1. This discovery explained the mechanism of toxin-induced blistering, since Dsg1 proteolysis compromises desmosomes, which link keratinocytes and support epidermal integrity. Here, we review clinical findings in ET-mediated disease, the characterization of ET, the molecular pathogenesis of bullous impetigo/staphylococcal scalded-skin syndrome, the structure and function of Dsg1, and current and potential treatments of ET-mediated disease.
Financial & competing interests disclosure
Cory L Simpson is supported by a Kirschstein National Research Service Award from the National Institute of Environmental Health Sciences (NIH F30 ES14990), a Presidential Fellowship from Northwestern University and a Malkin Family Scholarship from the Robert H Lurie Comprehensive Cancer Center of Northwestern University. Kathleen J Green is supported by research grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH R01 AR041836) and by an endowment from the Joseph L Mayberry Foundation. Spiro Getsios is supported by a Career Development Award from the Dermatology Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.