Removal of amino-terminal extracellular domains of desmoglein 1 by staphylococcal exfoliative toxin is sufficient to initiate epidermal blister formation.
BACKGROUND
In both bullous impetigo and staphylococcal scalded-skin syndrome (SSSS), exfoliative toxins (ETs) produced by Staphylococcus aureus cause superficial intraepidermal blisters. ETs are known to cleave specifically a single peptide bond in the extracellular domains 3 and 4 of desmoglein (Dsg) 1. However, the precise mechanisms underlying ET-induced epidermal blister formation remain poorly understood.


OBJECTIVE
To determine whether cleavage of Dsg1 by an ET is sufficient to induce blister formation in vivo or if the subsequent internalization of cleaved Dsg1 or other desmosomal components is required.


METHODS
Skin samples obtained from neonatal mice injected with ETA were analyzed by time-lapse immunofluorescence and transmission electron microscopy for desmosomal components.


RESULTS
Epidermal blister formation was observed as early as 60 min after ETA treatment. At this time, the amino-terminal extracellular domains of Dsg1 disappeared from the surface of keratinocytes, while the cleaved carboxy-terminal domain of Dsg1 (Dsg1-C) as well as the extracellular domains of desmocollin 1 (Dsc1-N) remained on the cell surface. Half-split desmosomes with intracytoplasmic dense plaques and attached tonofilaments were recognized ultrastructurally on the split surface of keratinocytes at 60 min. Subsequent to this, Dsg1-C and Dsc1-N gradually disappeared from the surface layer of keratinocytes.


CONCLUSIONS
Our findings suggest that the removal of amino-terminal extracellular domains of Dsg1 by ETs is sufficient to initiate epidermal blister formation in bullous impetigo and SSSS.
Nishifuji
Koji
K
Department of Dermatology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
Shimizu
Atsushi
A
Ishiko
Akira
A
Iwasaki
Toshiroh
T
Amagai
Masayuki
M
D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001768:Blister / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051183:Desmoglein 1 / Q000737:chemistry / Q000378:metabolism*; D003896:Desmosomes / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004817:Epidermis / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D005083:Exfoliatins / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D007169:Impetigo / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D017434:Protein Structure, Tertiary; D013206:Staphylococcal Scalded Skin Syndrome / Q000378:metabolism* / Q000473:pathology; D013211:Staphylococcus aureus
D000596:Amino Acids; D051183:Desmoglein 1; D005083:Exfoliatins