Abstract
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.
Highlights
Streptococcus pyogenes causes a broad spectrum of cutaneous infections, ranging from superficial streptococcal pyoderma to moderately severe cellulitis and even life-threatening necrotizing fasciitis
To examine whether S. pyogenes causes dysfunction of DMs, culture supernatants from strains with various serotypes recovered from both invasive and non-invasive diseases were incubated with the extracellular domain of human desmoglein 1 (Dsg1) or desmoglein 3 (Dsg3), cleavage of desmogleins was analyzed using western blot analysis (Figure 1)
These results suggest that several S. pyogenes strains secrete a protease responsible for the ectodomain shedding of Dsg1 and Dsg3
Summary
Streptococcus pyogenes causes a broad spectrum of cutaneous infections, ranging from superficial streptococcal pyoderma to moderately severe cellulitis and even life-threatening necrotizing fasciitis. Epidemiological data have shown an association with subsequent development of post-infectious glomerulonephritis and invasive diseases in patients with streptococcal pyoderma, which has important implications for their prognosis. It is likely that intraepidermal invasion of S. pyogenes through sites of abrasions, minor trauma, or insect bites is required for development of superficial skin infection (Stevens and Bryant, 2016). We recently reported that S. pyogenes possesses several strategies for TJ and AJ destabilization allowing for bacterial penetration via a paracellular route, SpeB Function in Cutaneous Infection raising the possibility that disruption of the keratinocyte barrier by colonized S. pyogenes leads to pyoderma development (Sumitomo et al, 2011, 2013, 2016; Sumitomo, 2015)
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