Staphylococcal exfoliative toxin B specifically cleaves desmoglein 1

Area of Science:

• Dermatology
• Microbiology
• Molecular Biology

Background:

• Staphylococcal Scalded Skin Syndrome (SSSS) and bullous impetigo are superficial blistering diseases caused by Staphylococcus aureus exfoliative toxins.
• Exfoliative toxin A (ETA) was previously shown to cleave desmoglein 1 (DSG1), a critical desmosomal adhesion molecule, leading to blister formation.
• The molecular target of exfoliative toxin B (ETB) remained undetermined.

Purpose of the Study:

• To identify the specific molecular target of exfoliative toxin B (ETB).
• To elucidate the mechanism by which ETB induces superficial epidermal blistering.
• To compare the molecular mechanisms of ETA and ETB in causing SSSS and bullous impetigo.

Main Methods:

• In vivo studies using neonatal mice injected with ETB.
• In vitro studies using adenovirus-transduced cultured keratinocytes expressing DSG1 or DSG3.
• Incubation of normal human skin cryosections with ETB.
• In vitro cleavage assays using recombinant extracellular domains of DSG1 and DSG3 with ETB.

Main Results:

• ETB injection in mice caused superficial epidermal blisters and degraded DSG1, without affecting DSG3 or E-cadherin.
• ETB specifically cleaved DSG1, but not DSG3, in cultured keratinocytes and human skin cryosections.
• ETB directly cleaved recombinant DSG1 (both mouse and human) in a dose-dependent manner, while DSG3 remained unaffected.

Conclusions:

• Exfoliative toxin B (ETB) targets and cleaves desmoglein 1 (DSG1), identical to the mechanism of exfoliative toxin A (ETA).
• Both ETA and ETB induce blister formation in SSSS and bullous impetigo through the same molecular mechanism: DSG1 cleavage.
• These findings unify the understanding of the molecular pathogenesis of SSSS and bullous impetigo.