Streptococcus pyogenes is responsible for a wide variety of cutaneous infections 
ranging from superficial impetigo to fulminant invasive necrotizing fasciitis. 
Dysfunction of desmosomes is associated with the pathogenesis of cutaneous 
diseases. We identified streptococcal pyrogenic exotoxin B (SpeB) as a 
proteolytic factor that cleaves the extracellular domains of desmoglein 1 and 3. 
In an epicutaneous infection model, lesional skin infected with an speB deletion 
mutant were significantly smaller as compared to those caused by the wild-type 
strain. Furthermore, immunohistological analysis indicated cleavage of 
desmogleins that developed around the invasion site of the wild-type strain. In 
contrast, the speB mutant was preferentially found on the epidermis surface 
layer. Taken together, our findings provide evidence that SpeB-mediated 
degradation of desmosomes has a pathogenic role in development of S. pyogenes 
cutaneous infection.