Toxin in bullous impetigo and staphylococcal scalded-skin syndrome targetsdesmoglein 1

Exfoliative toxin A, produced by Staphylococcus aureus, causes blisters in bullous impetigo and its more generalized form, staphylococcal scalded-skin syndrome(1-3). The toxin shows exquisite specificity in causing loss of ce ll adhesion only in the superficial epidermis. Although exfoliative toxin A has the structure of a serine protease, a target protein has not been iden tified(4,5). Desmoglein (Dsg) 1, a desmosomal cadherin that mediates cell-c ell adhesion, may be the target of exfoliative toxin A, because it is the t arget of autoantibodies in pemphigus foliaceus, in which blisters form with identical tissue specificity and histology. We show here that exfoliative toxin A cleaved mouse and human Dsg1, but not closely related cadherins suc h as Dsg3. We demonstrate this specific cleavage in cell culture, in neonat al mouse skin and with recombinant Dsg1, and conclude that Dsg1 is the spec ific receptor for exfoliative toxin A cleavage. This unique proteolytic att ack on the desmosome causes a blister just below the stratum corneum, which forms the epidermal barrier, presumably allowing the bacteria in bullous i mpetigo to proliferate and spread beneath this barrier.