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Toxin in bullous impetigo and staphylococcal scalded-skin syndrome targets desmoglein 1

Abstract

Exfoliative toxin A, produced by Staphylococcus aureus, causes blisters in bullous impetigo and its more generalized form, staphylococcal scalded-skin syndrome1,2,3. The toxin shows exquisite specificity in causing loss of cell adhesion only in the superficial epidermis. Although exfoliative toxin A has the structure of a serine protease, a target protein has not been identified4,5. Desmoglein (Dsg) 1, a desmosomal cadherin that mediates cell–cell adhesion, may be the target of exfoliative toxin A, because it is the target 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 such as Dsg3. We demonstrate this specific cleavage in cell culture, in neonatal mouse skin and with recombinant Dsg1, and conclude that Dsg1 is the specific receptor for exfoliative toxin A cleavage. This unique proteolytic attack on the desmosome causes a blister just below the stratum corneum, which forms the epidermal barrier, presumably allowing the bacteria in bullous impetigo to proliferate and spread beneath this barrier.

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Figure 1: Neonatal mice injected with ETA and pemphigus foliaceus antibodies.
Figure 2: Western blot analyses showing degradation of mouse Dsg1, but not mouse Dsg3 or epithelial cadherin.
Figure 3: Western blot analyses showing degradation of the recombinant extracellular domain of mouse and human Dsg1, but not Dsg3, with ETA.

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Acknowledgements

This work was supported by grants from the National Institute of Arthritis, Musculoskeletal, and Skin Diseases, and Grants for Research on Specific Diseases from the Ministry of Health and Welfare of Japan.

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Correspondence to J. R. Stanley.

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Amagai, M., Matsuyoshi, N., Wang, Z. et al. Toxin in bullous impetigo and staphylococcal scalded-skin syndrome targets desmoglein 1. Nat Med 6, 1275–1277 (2000). https://doi.org/10.1038/81385

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