Staphylococcal exfoliative toxin B specifically cleaves desmoglein 1.

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.

• Authors: Masayuki Amagai, Takayuki Yamaguchi, Yasushi Hanakawa, Koji Nishifuji, Motoyuki Sugai, John R Stanley
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 118 Issue 5 Pg. 845-50 (May 2002) ISSN: 0022-202X [Print] United States
• PMID: 11982763 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cadherins
• DSG3 protein, human
• Desmoglein 1
• Desmoglein 3
• Exfoliatins
• Recombinant Proteins

Topics

• Animals
• Animals, Newborn
• Blister (metabolism, pathology)
• Cadherins (genetics, metabolism)
• Cells, Cultured
• Desmoglein 1
• Desmoglein 3
• Epidermis (metabolism, pathology)
• Exfoliatins (metabolism, pharmacology)
• Humans
• Keratinocytes (cytology, drug effects, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred ICR
• Recombinant Proteins (genetics, metabolism)
• Staphylococcal Scalded Skin Syndrome (metabolism, pathology)