Staphylococcal exfoliative toxin B specifically cleaves desmoglein 1

Masayuki Amagai, Takayuki Yamaguchi, Yasushi Hanakawa, Koji Nishifuji, Motoyuki Sugai, John R. Stanley

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

Staphylococcal scalded skin syndrome and its localized form, bullous impetigo, show superficial epidermal blister formation caused by exfoliative toxin A or B produced by Staphylococcus aureus. Recently we have demonstrated that exfoliative toxin A specifically cleaves desmoglein 1, a desmosomal adhesion molecule, that when inactivated results in blisters. In this study we determine the target molecule for exfoliative toxin B. Exfoliative toxin B injected in neonatal mice caused superficial epidermal blisters, abolished cell surface staining of desmoglein 1, and degraded desmoglein 1 without affecting desmoglein 3 or E-cadherin. When adenovirus-transduced cultured keratinocytes expressing exogenous mouse desmoglein 1 or desmoglein 3 were incubated with exfoliative toxin B, desmoglein 1, but not desmoglein 3, was cleaved. Furthermore, cell surface staining of desmoglein 1, but not that of desmoglein 3, was abolished when cryosections of normal human skin were incubated with exfoliative toxin B, suggesting that living cells were not necessary for exfoliative toxin B cleavage of desmoglein 1. Finally, in vitro incubation of the recombinant extracellular domains of desmoglein 1 and desmoglein 3 with exfoliative toxin B demonstrated that both mouse and human desmoglein 1, but not desmoglein 3, were directly cleaved by exfoliative toxin B in a dose-dependent fashion. These findings demonstrate that exfoliative toxin A and exfoliative toxin B cause blister formation in staphylococcal scalded skin syndrome and bullous impetigo by identical molecular pathophysiologic mechanisms.

Original languageEnglish
Pages (from-to)845-850
Number of pages6
JournalJournal of Investigative Dermatology
Volume118
Issue number5
DOIs
Publication statusPublished - 2002

Fingerprint

Exfoliatins
Desmoglein 1
Desmoglein 3
Blister
Staphylococcal Scalded Skin Syndrome
Impetigo
Skin
Staining and Labeling
Molecules
Cadherins
Keratinocytes
Adenoviridae
Staphylococcus aureus

Keywords

  • Cadherin
  • Impetigo
  • Pemphigus foliaceus
  • Skin infection
  • SSSS

ASJC Scopus subject areas

  • Dermatology

Cite this

Staphylococcal exfoliative toxin B specifically cleaves desmoglein 1. / Amagai, Masayuki; Yamaguchi, Takayuki; Hanakawa, Yasushi; Nishifuji, Koji; Sugai, Motoyuki; Stanley, John R.

In: Journal of Investigative Dermatology, Vol. 118, No. 5, 2002, p. 845-850.

Research output: Contribution to journalArticle

Amagai, M, Yamaguchi, T, Hanakawa, Y, Nishifuji, K, Sugai, M & Stanley, JR 2002, 'Staphylococcal exfoliative toxin B specifically cleaves desmoglein 1', Journal of Investigative Dermatology, vol. 118, no. 5, pp. 845-850. https://doi.org/10.1046/j.1523-1747.2002.01751.x
Amagai, Masayuki ; Yamaguchi, Takayuki ; Hanakawa, Yasushi ; Nishifuji, Koji ; Sugai, Motoyuki ; Stanley, John R. / Staphylococcal exfoliative toxin B specifically cleaves desmoglein 1. In: Journal of Investigative Dermatology. 2002 ; Vol. 118, No. 5. pp. 845-850.
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