Targeting of desmoglein 1 in exfoliative toxin-mediated disease

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.