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


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.


  1. Farrell, A.M. Staphylococcal scalded-skin syndrome. Lancet 354, 880–881 (1999).

    CAS  Article  Google Scholar 

  2. Melish, M.E. & Glasgow, L.A. Staphylococcal scalded skin syndrome: The expanded clinical syndrome. J. Pediatrics 78, 958–967 (1971).

    CAS  Article  Google Scholar 

  3. Elias, P.M., Fritsch, P. & Epstein, Jr. E.H. Staphylococcal scalded skin syndrome. Clinical features, pathogenesis, and recent microbiological and biochemical developments. Arch. Dermatol. 113, 207– 219 (1977).

    CAS  Article  Google Scholar 

  4. Dancer, S.J., Garratt, R., Saldanha, J., Jhoti, H. & Evans, R. The epidermolytic toxins are serine proteases. FEBS Letters 268, 129– 132 (1990).

    CAS  Article  Google Scholar 

  5. Vath, G.M. et al. The structure of the superantigen exfoliative toxin A suggests a novel regulation as a serine protease. Biochemistry 36, 1559–1566 (1997).

    CAS  Article  Google Scholar 

  6. Lyell, A. The staphylococcal scalded skin syndrome in historical perspective: emergence of dermopathic strains of Staphylococcal aureus and discovery of the epidermolytic toxin. J. Am. Acad. Dermatol. 9, 285–294 (1983).

    CAS  Article  Google Scholar 

  7. Rago, J.V., Vath, G.M., Bohach, G.A., Ohlendorf, D.H. & Schlievert, P.M. Mutational analysis of the superantigen staphylococcal exfoliative toxin A (ETA). J. Immunol. 164, 2207–2213 (2000).

    CAS  Article  Google Scholar 

  8. Mahoney, M.G. et al. Explanation for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. J. Clin. Invest. 103, 461–468 ( 1999).

    CAS  Article  Google Scholar 

  9. Melish, M.E. & Glasgow, L.A. The staphylococcal scalded-skin syndrome. Development of an experimental model. N. Engl. J. Med. 282, 1114–1119 (1970).

    CAS  Article  Google Scholar 

  10. Nilles, L.A. et al. Structural analysis and expression of human desmoglein: a cadherin-like component of the desmosome. J. Cell Science 99, 809–821 (1991).

    PubMed  Google Scholar 

  11. Koch, P.J. et al. Desmoglein 3 anchors telogen hair in the follicle. J. Cell Sci. 111, 2529–2537 (1998).

    CAS  PubMed  Google Scholar 

  12. Hopp, T.P. et al. A short polypeptide marker sequence useful for recombinant protein identification and purification. Biotechnology 6, 1205–1210 (1988).

    Google Scholar 

  13. Ishikawa, H. et al. cDNA cloning and chromosomal assignment of the mouse gene for desmoglein 3 (Dsg3), the pemphigus vulgaris antigen. Mammalian Genome 5, 803–804 ( 1994).

    CAS  Article  Google Scholar 

  14. Ishikawa, H., Li, K., Sawamura, D. & Uitto, J. Cloning of the mouse desmoglein 3 gene (Dsg3): interspecies conservation within the cadherin superfamily. Exp. Dermatol. 9, 229– 239 (2000).

    CAS  Article  Google Scholar 

  15. Wu, H. et al. Protection of neonates against pemphigus foliaceus by desmoglein 3. N. Engl. J. Med. 343, 31– 35 (2000).

    CAS  Article  Google Scholar 

  16. Shirayoshi, Y., Nose, A., Iwasaki, K. & Takeichi, M. N-linked oligosaccharides are not involved in the function of a cell-cell binding glycoprotein E-cadherin. Cell Struct. Funct. 11, 245–252 (1986).

    CAS  Article  Google Scholar 

  17. Ishii, K. et al. Characterization of autoantibodies in pemphigus using antigen-specific enzyme-linked immunosorbent assays with baculovirus-expressed recombinant desmogleins. J. Immunol. 159, 2010– 2017 (1997).

    CAS  PubMed  Google Scholar 

  18. Amagai, M. et al. Use of autoantigen-knockout mice in developing an active autoimmune disease model for pemphigus. J. Clin. Invest. 105, 625–631 (2000).

    CAS  Article  Google Scholar 

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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).

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